presentation of type 2 diabetes mellitus

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Type 2 diabetes is a condition that happens because of a problem in the way the body regulates and uses sugar as a fuel. That sugar also is called glucose. This long-term condition results in too much sugar circulating in the blood. Eventually, high blood sugar levels can lead to disorders of the circulatory, nervous and immune systems.

In type 2 diabetes, there are primarily two problems. The pancreas does not produce enough insulin — a hormone that regulates the movement of sugar into the cells. And cells respond poorly to insulin and take in less sugar.

Type 2 diabetes used to be known as adult-onset diabetes, but both type 1 and type 2 diabetes can begin during childhood and adulthood. Type 2 is more common in older adults. But the increase in the number of children with obesity has led to more cases of type 2 diabetes in younger people.

There's no cure for type 2 diabetes. Losing weight, eating well and exercising can help manage the disease. If diet and exercise aren't enough to control blood sugar, diabetes medications or insulin therapy may be recommended.

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Symptoms of type 2 diabetes often develop slowly. In fact, you can be living with type 2 diabetes for years and not know it. When symptoms are present, they may include:

• Increased thirst.
• Frequent urination.
• Increased hunger.
• Unintended weight loss.
• Blurred vision.
• Slow-healing sores.
• Frequent infections.
• Numbness or tingling in the hands or feet.
• Areas of darkened skin, usually in the armpits and neck.

When to see a doctor

See your health care provider if you notice any symptoms of type 2 diabetes.

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Type 2 diabetes is mainly the result of two problems:

• Cells in muscle, fat and the liver become resistant to insulin As a result, the cells don't take in enough sugar.
• The pancreas can't make enough insulin to keep blood sugar levels within a healthy range.

Exactly why this happens is not known. Being overweight and inactive are key contributing factors.

How insulin works

Insulin is a hormone that comes from the pancreas — a gland located behind and below the stomach. Insulin controls how the body uses sugar in the following ways:

• Sugar in the bloodstream triggers the pancreas to release insulin.
• Insulin circulates in the bloodstream, enabling sugar to enter the cells.
• The amount of sugar in the bloodstream drops.
• In response to this drop, the pancreas releases less insulin.

The role of glucose

Glucose — a sugar — is a main source of energy for the cells that make up muscles and other tissues. The use and regulation of glucose includes the following:

• Glucose comes from two major sources: food and the liver.
• Glucose is absorbed into the bloodstream, where it enters cells with the help of insulin.
• The liver stores and makes glucose.
• When glucose levels are low, the liver breaks down stored glycogen into glucose to keep the body's glucose level within a healthy range.

In type 2 diabetes, this process doesn't work well. Instead of moving into the cells, sugar builds up in the blood. As blood sugar levels rise, the pancreas releases more insulin. Eventually the cells in the pancreas that make insulin become damaged and can't make enough insulin to meet the body's needs.

Risk factors

Factors that may increase the risk of type 2 diabetes include:

• Weight. Being overweight or obese is a main risk.
• Fat distribution. Storing fat mainly in the abdomen — rather than the hips and thighs — indicates a greater risk. The risk of type 2 diabetes is higher in men with a waist circumference above 40 inches (101.6 centimeters) and in women with a waist measurement above 35 inches (88.9 centimeters).
• Inactivity. The less active a person is, the greater the risk. Physical activity helps control weight, uses up glucose as energy and makes cells more sensitive to insulin.
• Family history. An individual's risk of type 2 diabetes increases if a parent or sibling has type 2 diabetes.
• Race and ethnicity. Although it's unclear why, people of certain races and ethnicities — including Black, Hispanic, Native American and Asian people, and Pacific Islanders — are more likely to develop type 2 diabetes than white people are.
• Blood lipid levels. An increased risk is associated with low levels of high-density lipoprotein (HDL) cholesterol — the "good" cholesterol — and high levels of triglycerides.
• Age. The risk of type 2 diabetes increases with age, especially after age 35.
• Prediabetes. Prediabetes is a condition in which the blood sugar level is higher than normal, but not high enough to be classified as diabetes. Left untreated, prediabetes often progresses to type 2 diabetes.
• Pregnancy-related risks. The risk of developing type 2 diabetes is higher in people who had gestational diabetes when they were pregnant and in those who gave birth to a baby weighing more than 9 pounds (4 kilograms).
• Polycystic ovary syndrome. Having polycystic ovary syndrome — a condition characterized by irregular menstrual periods, excess hair growth and obesity — increases the risk of diabetes.

Complications

Type 2 diabetes affects many major organs, including the heart, blood vessels, nerves, eyes and kidneys. Also, factors that increase the risk of diabetes are risk factors for other serious diseases. Managing diabetes and controlling blood sugar can lower the risk for these complications and other medical conditions, including:

• Heart and blood vessel disease. Diabetes is associated with an increased risk of heart disease, stroke, high blood pressure and narrowing of blood vessels, a condition called atherosclerosis.
• Nerve damage in limbs. This condition is called neuropathy. High blood sugar over time can damage or destroy nerves. That may result in tingling, numbness, burning, pain or eventual loss of feeling that usually begins at the tips of the toes or fingers and gradually spreads upward.
• Other nerve damage. Damage to nerves of the heart can contribute to irregular heart rhythms. Nerve damage in the digestive system can cause problems with nausea, vomiting, diarrhea or constipation. Nerve damage also may cause erectile dysfunction.
• Kidney disease. Diabetes may lead to chronic kidney disease or end-stage kidney disease that can't be reversed. That may require dialysis or a kidney transplant.
• Eye damage. Diabetes increases the risk of serious eye diseases, such as cataracts and glaucoma, and may damage the blood vessels of the retina, potentially leading to blindness.
• Skin conditions. Diabetes may raise the risk of some skin problems, including bacterial and fungal infections.
• Slow healing. Left untreated, cuts and blisters can become serious infections, which may heal poorly. Severe damage might require toe, foot or leg amputation.
• Hearing impairment. Hearing problems are more common in people with diabetes.
• Sleep apnea. Obstructive sleep apnea is common in people living with type 2 diabetes. Obesity may be the main contributing factor to both conditions.
• Dementia. Type 2 diabetes seems to increase the risk of Alzheimer's disease and other disorders that cause dementia. Poor control of blood sugar is linked to a more rapid decline in memory and other thinking skills.

Healthy lifestyle choices can help prevent type 2 diabetes. If you've received a diagnosis of prediabetes, lifestyle changes may slow or stop the progression to diabetes.

A healthy lifestyle includes:

• Eating healthy foods. Choose foods lower in fat and calories and higher in fiber. Focus on fruits, vegetables and whole grains.
• Getting active. Aim for 150 or more minutes a week of moderate to vigorous aerobic activity, such as a brisk walk, bicycling, running or swimming.
• Losing weight. If you are overweight, losing a modest amount of weight and keeping it off may delay the progression from prediabetes to type 2 diabetes. If you have prediabetes, losing 7% to 10% of your body weight may reduce the risk of diabetes.
• Avoiding long stretches of inactivity. Sitting still for long periods of time can increase the risk of type 2 diabetes. Try to get up every 30 minutes and move around for at least a few minutes.

For people with prediabetes, metformin (Fortamet, Glumetza, others), a diabetes medication, may be prescribed to reduce the risk of type 2 diabetes. This is usually prescribed for older adults who are obese and unable to lower blood sugar levels with lifestyle changes.

More Information

• Diabetes prevention: 5 tips for taking control
• Professional Practice Committee: Standards of Medical Care in Diabetes — 2020. Diabetes Care. 2020; doi:10.2337/dc20-Sppc.
• Diabetes mellitus. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetes-mellitus-dm. Accessed Dec. 7, 2020.
• Melmed S, et al. Williams Textbook of Endocrinology. 14th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Dec. 3, 2020.
• Diabetes overview. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/all-content. Accessed Dec. 4, 2020.
• AskMayoExpert. Type 2 diabetes. Mayo Clinic; 2018.
• Feldman M, et al., eds. Surgical and endoscopic treatment of obesity. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 11th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed Oct. 20, 2020.
• Hypersmolar hyperglycemic state (HHS). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hyperosmolar-hyperglycemic-state-hhs. Accessed Dec. 11, 2020.
• Diabetic ketoacidosis (DKA). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka. Accessed Dec. 11, 2020.
• Hypoglycemia. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hypoglycemia. Accessed Dec. 11, 2020.
• 6 things to know about diabetes and dietary supplements. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/tips/things-to-know-about-type-diabetes-and-dietary-supplements. Accessed Dec. 11, 2020.
• Type 2 diabetes and dietary supplements: What the science says. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/providers/digest/type-2-diabetes-and-dietary-supplements-science. Accessed Dec. 11, 2020.
• Preventing diabetes problems. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/all-content. Accessed Dec. 3, 2020.
• Schillie S, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and Reports. 2018; doi:10.15585/mmwr.rr6701a1.
• Caffeine: Does it affect blood sugar?
• GLP-1 agonists: Diabetes drugs and weight loss
• Hyperinsulinemia: Is it diabetes?
• Medications for type 2 diabetes

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Type 2 Diabetes

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What is type 2 diabetes?

Who is more likely to develop type 2 diabetes, what are the symptoms of diabetes, what causes type 2 diabetes, how do health care professionals diagnose type 2 diabetes, how can i manage my type 2 diabetes, what medicines do i need to treat my type 2 diabetes, what health problems can people with diabetes develop, how can i lower my chances of developing type 2 diabetes.

Type 2 diabetes, the most common type of diabetes, is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of energy and comes mainly from the food you eat. Insulin , a hormone made by the pancreas , helps glucose get into your cells to be used for energy. In type 2 diabetes, your body doesn’t make enough insulin or doesn’t use insulin well. Too much glucose then stays in your blood, and not enough reaches your cells.

The good news is that you can take steps to prevent or delay the development of type 2 diabetes.

You can develop type 2 diabetes at any age, even during childhood. However, type 2 diabetes occurs most often in middle-aged and older people. You are more likely to develop type 2 diabetes if you are age 45 or older, have a family history of diabetes, or are overweight or have obesity . Diabetes is more common in people who are African American, Hispanic/Latino, American Indian, Asian American, or Pacific Islander.

Physical inactivity and certain health problems such as high blood pressure affect your chances of developing type 2 diabetes. You are also more likely to develop type 2 diabetes if you have prediabetes or had gestational diabetes when you were pregnant. Learn more about risk factors for type 2 diabetes .

Symptoms of diabetes include

• increased thirst and urination
• increased hunger
• feeling tired
• blurred vision
• numbness or tingling in the feet or hands
• sores that do not heal
• unexplained weight loss

Symptoms of type 2 diabetes often develop slowly—over the course of several years—and can be so mild that you might not even notice them. Many people have no symptoms. Some people do not find out they have the disease until they have diabetes-related health problems, such as blurred vision or heart disease .

Type 2 diabetes is caused by several factors, including

• overweight and obesity
• not being physically active
• insulin resistance

Learn more about the causes of type 2 diabetes .

Your health care professional can diagnose type 2 diabetes based on blood tests. Learn more about blood tests for diabetes and what the results mean.

Managing your blood glucose, blood pressure , and cholesterol , and quitting smoking if you smoke, are important ways to manage your type 2 diabetes . Lifestyle changes that include planning healthy meals, limiting calories if you are overweight, and being physically active are also part of managing your diabetes. So is taking any prescribed medicines. Work with your health care team to create a diabetes care plan that works for you.

Along with following your diabetes care plan, you may need diabetes medicines, which may include pills or medicines you inject under your skin, such as insulin. Over time, you may need more than one diabetes medicine to manage your blood glucose. Even if you don’t take insulin, you may need it at special times, such as during pregnancy or if you are in the hospital. You also may need medicines for high blood pressure, high cholesterol, or other conditions.

Learn more about medicines, insulin, and other diabetes treatments .

Following a good diabetes care plan can help protect against many diabetes-related health problems. However, if not managed, diabetes can lead to problems such as

• heart disease and stroke
• nerve damage
• kidney disease
• foot problems
• eye disease
• gum disease and other dental problems
• sexual and bladder problems

Many people with type 2 diabetes also have nonalcoholic fatty liver disease (NAFLD) . Losing weight if you are overweight or have obesity can improve NAFLD. Diabetes is also linked to other health problems such as sleep apnea , depression, some types of cancer, and dementia .

You can take steps to lower your chances of developing these diabetes-related health problems .

Research such as the Diabetes Prevention Program , sponsored by the National Institutes of Health, has shown that you can take steps to reduce your chances of developing type 2 diabetes if you have risk factors for the disease. Here are some things you can do to lower your risk:

• Lose weight if you are overweight, and keep it off. You may be able to prevent or delay diabetes by losing 5 to 7 percent of your current weight. 1 For instance, if you weigh 200 pounds, your goal would be to lose about 10 to 14 pounds.  
• Move more. Get at least 30 minutes of physical activity, such as walking, at least 5 days a week. If you have not been active, talk with your health care professional about which activities are best. Start slowly and build up to your goal.
• Eat healthy foods. Eat smaller portions to reduce the amount of calories you eat each day and help you lose weight. Choosing foods with less fat is another way to reduce calories. Drink water instead of sweetened beverages.

Ask your health care team what other changes you can make to prevent or delay type 2 diabetes.

Most often, your best chance for preventing type 2 diabetes is to make lifestyle changes that work for you long term. Get started with Your Game Plan to Prevent Type 2 Diabetes .

This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by NIDDK is carefully reviewed by NIDDK scientists and other experts.

The NIDDK would like to thank: Rita Basu, M.D., Mayo Clinic

• Type 2 Diabetes Mellitus
• Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
• Sections Type 2 Diabetes Mellitus
• Practice Essentials
• Pathophysiology
• Epidemiology
• Patient Education
• Physical Examination
• Approach Considerations
• Glucose Studies
• Glycated Hemoglobin Studies
• Urinary Albumin Studies
• Diabetes Testing in Asymptomatic Patients
• Tests to Differentiate Type 2 and Type 1 Diabetes
• Pharmacologic Therapy
• Management of Glycemia
• Dietary Modifications
• Activity Modifications
• Bariatric Surgery
• Laboratory Monitoring
• Monitoring for Diabetic Complications
• Management of Hypertension
• Management of Dyslipidemia
• Management of Coronary Heart Disease
• Management of Ophthalmologic Complications
• Management of Diabetic Neuropathy
• Management of Infections
• Management of Intercurrent Medical Illness
• Management of Critical Illness
• Pharmacologic Considerations in Surgery
• Prevention of Type 2 Diabetes Mellitus
• Stroke Prevention in Diabetes
• Consultations
• Medication Summary
• Antidiabetics, Biguanides
• Antidiabetics, Sulfonylureas
• Antidiabetics, Meglitinide Derivatives
• Antidiabetics, Alpha-Glucosidase Inhibitors
• Antidiabetics, Thiazolidinediones
• Antidiabetics, Glucagonlike Peptide-1 Agonists
• Dual GIP/GLP-1 Agonists
• Antidiabetics, Dipeptidyl Peptidase IV Inhibitors
• Antidiabetics, Amylinomimetics
• Selective Sodium-Glucose Transporter-2 Inhibitors
• Bile Acid Sequestrants
• Antidiabetics, Rapid-Acting Insulins
• Antidiabetics, Short-Acting Insulins
• Antidiabetics, Intermediate-Acting Insulins
• Antidiabetics, Long-Acting Insulins
• Dopamine Agonists
• Questions & Answers
• Media Gallery

Type 2 diabetes mellitus consists of an array of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. See the image below.

Signs and symptoms

Many patients with type 2 diabetes are asymptomatic. Clinical manifestations include the following:

Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss

Blurred vision

Lower-extremity paresthesias

Yeast infections (eg, balanitis in men)

See Presentation for more detail.

Diagnostic criteria by the American Diabetes Association (ADA) include the following [ 1 ] :

A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or

A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or

A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis

Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher should be a primary diagnostic criterion or an optional criterion remains a point of controversy.

Indications for diabetes screening in asymptomatic adults includes the following [ 2 , 3 , 4 , 5 ] :

Sustained blood pressure >135/80 mm Hg

Overweight and 1 or more other risk factors for diabetes (eg, first-degree relative with diabetes, BP 140/90 mm Hg or above, and HDL < 35 mg/dL and/or triglyceride level >250 mg/dL)

The ADA recommends screening at age 35 years in the absence of the above criteria

See Workup for more detail.

Goals of treatment are as follows:

Microvascular (ie, eye and kidney disease) risk reduction through control of glycemia and blood pressure

Macrovascular (ie, coronary, cerebrovascular, peripheral vascular) risk reduction through control of lipids and hypertension, smoking cessation

Metabolic and neurologic risk reduction through control of glycemia

Recommendations for the treatment of type 2 diabetes mellitus from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) place the patient's condition, desires, abilities, and tolerances at the center of the decision-making process. [ 6 , 7 , 8 ]

The EASD/ADA position statement contains 7 key points:

Individualized glycemic targets and glucose-lowering therapies

Diet, exercise, and education as the foundation of the treatment program

Use of metformin as the optimal first-line drug unless contraindicated

After metformin, the use of 1 or 2 additional oral or injectable agents, with a goal of minimizing adverse effects if possible

Ultimately, insulin therapy alone or with other agents if needed to maintain blood glucose control

Where possible, all treatment decisions should involve the patient, with a focus on patient preferences, needs, and values

A major focus on comprehensive cardiovascular risk reduction

The 2013 ADA guidelines for self-monitoring of blood glucose (SMBG) frequency focus on an individual's specific situation rather than quantifying the number of tests that should be done. The recommendations include the following [ 9 , 10 ] :

Patients on intensive insulin regimens – Perform SMBG at least before meals and snacks, as well as occasionally after meals; at bedtime; before exercise and before critical tasks (eg, driving); when hypoglycemia is suspected; and after treating hypoglycemia until normoglycemia is achieved.

Patients using less frequent insulin injections or noninsulin therapies – Use SMBG results to adjust to food intake, activity, or medications to reach specific treatment goals; clinicians must not only educate these individuals on how to interpret their SMBG data, but they should also reevaluate the ongoing need for and frequency of SMBG at each routine visit.

Approaches to prevention of diabetic complications include the following:

HbA1c every 3-6 months

Yearly dilated eye examinations

Annual microalbumin checks

Foot examinations at each visit

Blood pressure below 130/80 mm Hg

Statin therapy to reduce low-density lipoprotein cholesterol

See Treatment and Medication for more detail.

Type 2 diabetes mellitus consists of an array of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. Poorly controlled type 2 diabetes is associated with an array of microvascular, macrovascular, and neuropathic complications.

Microvascular complications of diabetes include retinal, renal, and possibly neuropathic disease. Macrovascular complications include coronary artery and peripheral vascular disease. Diabetic neuropathy affects autonomic and peripheral nerves. (See Pathophysiology and Presentation.)

Unlike patients with type 1 diabetes mellitus , patients with type 2 are not absolutely dependent on insulin for life. This distinction was the basis for the older terms for types 1 and 2, insulin dependent and non–insulin dependent diabetes.

However, many patients with type 2 diabetes are ultimately treated with insulin. Because they retain the ability to secrete some endogenous insulin, they are considered to require insulin but not to depend on insulin. Nevertheless, given the potential for confusion due to classification based on treatment rather than etiology, the older terms have been abandoned. [ 11 ] Another older term for type 2 diabetes mellitus was adult-onset diabetes. Currently, because of the epidemic of obesity and inactivity in children, type 2 diabetes mellitus is occurring at younger and younger ages. Although type 2 diabetes mellitus typically affects individuals older than 40 years, it has been diagnosed in children as young as 2 years of age who have a family history of diabetes. In many communities, type 2 diabetes now outnumbers type 1 among children with newly diagnosed diabetes. (See Epidemiology.)

Diabetes mellitus is a chronic disease that requires long-term medical attention to limit the development of its devastating complications and to manage them when they do occur. It is a disproportionately expensive disease; in the United States in 2012, the direct and indirect costs of diagnosed diabetes were estimated to be $245 billion; people with diagnosed diabetes had average medical expenditures 2.3 times those of people without diabetes. [ 12 , 13 ]

This article focuses on the diagnosis and treatment of type 2 diabetes and its acute and chronic complications, other than those directly associated with hypoglycemia and severe metabolic disturbances, such as hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA). For more information on those topics, see Hyperosmolar Hyperglycemic State and Diabetic Ketoacidosis .

Type 2 diabetes is characterized by a combination of peripheral insulin resistance and inadequate insulin secretion by pancreatic beta cells. Insulin resistance, which has been attributed to elevated levels of free fatty acids and proinflammatory cytokines in plasma, leads to decreased glucose transport into muscle cells, elevated hepatic glucose production, and increased breakdown of fat.

A role for excess glucagon cannot be underestimated; indeed, type 2 diabetes is an islet paracrinopathy in which the reciprocal relationship between the glucagon-secreting alpha cell and the insulin-secreting beta cell is lost, leading to hyperglucagonemia and hence the consequent hyperglycemia. [ 14 ]

For type 2 diabetes mellitus to occur, both insulin resistance and inadequate insulin secretion must exist. For example, all overweight individuals have insulin resistance, but diabetes develops only in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Their insulin concentrations may be high, yet inappropriately low for the level of glycemia.

A simplified scheme for the pathophysiology of abnormal glucose metabolism in type 2 diabetes mellitus is depicted in the image below.

With prolonged diabetes, atrophy of the pancreas may occur. A study by Philippe et al used computed tomography (CT) scan findings, glucagon stimulation test results, and fecal elastase-1 measurements to confirm reduced pancreatic volume in individuals with a median 15-year history of diabetes mellitus (range, 5-26 years). [ 15 ] This may also explain the associated exocrine deficiency seen in prolonged diabetes.

Beta-cell dysfunction

Beta-cell dysfunction is a major factor across the spectrum of prediabetes to diabetes. A study of obese adolescents by Bacha et al confirms what is increasingly being stressed in adults as well: Beta-cell dysfunction develops early in the pathologic process and does not necessarily follow the stage of insulin resistance. [ 16 ] Singular focus on insulin resistance as the "be all and end all" is gradually shifting, and hopefully better treatment options that address the beta-cell pathology will emerge for early therapy.

Insulin resistance

In the progression from normal to abnormal glucose tolerance, postprandial blood glucose levels increase first. Eventually, fasting hyperglycemia develops as suppression of hepatic gluconeogenesis fails.

During the induction of insulin resistance (such as occurs with a high-calorie diet, steroid administration, or physical inactivity), increased glucagon levels and increased glucose-dependent insulinotropic polypeptide (GIP) levels accompany glucose intolerance . However, the postprandial glucagonlike peptide-1 (GLP-1) response is unaltered. [ 17 ]

Genomic factors

Genome-wide association studies of single-nucleotide polymorphisms (SNPs) have identified a number of genetic variants that are associated with beta-cell function and insulin resistance. Some of these SNPs appear to increase the risk for type 2 diabetes. Over 40 independent loci demonstrating an association with an increased risk for type 2 diabetes have been shown. [ 18 ] A subset of the most potent are shared below [ 19 ] :

Decreased beta-cell responsiveness, leading to impaired insulin processing and decreased insulin secretion ( TCF7L2)

Lowered early glucose-stimulated insulin release ( MTNR1B, FADS1, DGKB , GCK )

Altered metabolism of unsaturated fatty acids ( FSADS1 )

Dysregulation of fat metabolism ( PPARG )

Inhibition of serum glucose release ( KCNJ11 ) [ 20 ]

Increased adiposity and insulin resistance ( FTO and IGF2BP2 ) [ 21 , 22 ]

Control of the development of pancreatic structures, including beta-islet cells ( HHEX ) [ 23 ]

Transport of zinc into the beta-islet cells, which influences the production and secretion of insulin ( SLC30A8 ) [ 23 ]

Survival and function of beta-islet cells ( WFS1 ) [ 24 ]

Susceptibility to type 2 diabetes may also be affected by genetic variants involving incretin hormones, which are released from endocrine cells in the gut and stimulate insulin secretion in response to digestion of food. For example, reduced beta-cell function has been associated with a variant in the gene that codes for the receptor of gastric inhibitory polypeptide ( GIPR ). [ 25 ]

The high mobility group A1 (HMGA1) protein is a key regulator of the insulin receptor gene ( INSR ). [ 26 ] Functional variants of the HMGA1 gene are associated with an increased risk of diabetes.

Amino acid metabolism

Amino acid metabolism may play a key role early in the development of type 2 diabetes. Wang et al reported that the risk of future diabetes was at least 4-fold higher in normoglycemic individuals with high fasting plasma concentrations of 3 amino acids (isoleucine, phenylalanine, and tyrosine). Concentrations of these amino acids were elevated up to 12 years prior to the onset of diabetes. [ 27 ] In this study, amino acids, amines, and other polar metabolites were profiled using liquid chromatography tandem mass spectrometry.

Diabetes complications

Although the pathophysiology of the disease differs between the types of diabetes, most of the complications, including microvascular, macrovascular, and neuropathic, are similar regardless of the type of diabetes. Hyperglycemia appears to be the determinant of microvascular and metabolic complications. Macrovascular disease may be less related to glycemia.

Telomere attrition may be a marker associated with presence and the number of diabetic complications. Whether it is a cause or a consequence of diabetes remains to be seen. [ 28 ]

Cardiovascular risk

Cardiovascular risk in people with diabetes is related in part to insulin resistance, with the following concomitant lipid abnormalities:

Elevated levels of small, dense low-density lipoprotein (LDL) cholesterol particles

Low levels of high-density lipoprotein (HDL) cholesterol

Elevated levels of triglyceride-rich remnant lipoproteins

Thrombotic abnormalities (ie, elevated type-1 plasminogen activator inhibitor [PAI-1], elevated fibrinogen) and hypertension are also involved. Other conventional atherosclerotic risk factors (eg, family history, smoking, elevated LDL cholesterol) also affect cardiovascular risk.

Insulin resistance is associated with increased lipid accumulation in liver and smooth muscle, but not with increased myocardial lipid accumulation. [ 29 ] Persistent lipid abnormalities remain in patients with diabetes despite the use of lipid-modifying drugs, although evidence supports the benefits of these drugs. Statin dose up-titration and the addition of other lipid-modifying agents are needed. [ 30 ]

Increased cardiovascular risk appears to begin prior to the development of frank hyperglycemia, presumably because of the effects of insulin resistance. Stern in 1996 [ 31 ] and Haffner and D'Agostino in 1999 [ 32 ] developed the "ticking clock" hypothesis of complications, asserting that the clock starts ticking for microvascular risk at the onset of hyperglycemia, while the clock starts ticking for macrovascular risk at some antecedent point, presumably with the onset of insulin resistance.

The question of when diabetes becomes a cardiovascular risk equivalent has not yet been settled. Debate has moved beyond automatically considering diabetes a cardiovascular risk equivalent. Perhaps it would be prudent to assume the equivalency with diabetes that is more than 5-10 years in duration.

Cognitive decline

In a cross-sectional study of 350 patients aged 55 years and older with type 2 diabetes and 363 control participants aged 60 years and older without diabetes, diabetic individuals were more likely to have brain atrophy than cerebrovascular lesions, with patterns resembling those of preclinical Alzheimer disease. [ 33 , 34 ] Type 2 diabetes was associated with hippocampal atrophy; temporal, frontal, and limbic gray-matter atrophy; and, to a lesser extent, frontal and temporal white-matter atrophy.

Type 2 diabetes was also linked with poorer performance on certain cognitive tests. The strength of these associations dropped by almost 50% when adjusted for hippocampal and total gray-matter volumes but was unchanged when adjusted for cerebrovascular lesions or white-matter volume. [ 33 , 34 ] Patients with type 2 diabetes were more likely to have gray-matter atrophy in several bilateral regions of the cortices, especially in the left hemisphere, similar to the distribution of cortical atrophy described in early Alzheimer disease. [ 33 ]

In a 40-month study of 2977 middle-aged and older adults with long-standing type 2 diabetes, depression at baseline was associated with accelerated cognitive decline. [ 35 , 36 ] The 531 subjects with scores of 10 or higher on the Patient Health Questionnaire Depression Scale at baseline had significantly lower scores on the Digit Symbol Substitution Test (DSST), the Rey Auditory Verbal Learning Test (RAVLT), and the modified Stroop test. Adjustment for other risk factors did not affect the association.

Pulmonary disease

A British study indicated that high blood sugar in type 2 diabetes and prediabetes can directly result in lung complications such as restrictive lung disease, fibrosis, and pneumonia.  This was supported by a finding that greater blood glucose levels in type 2 diabetes reduce forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Between 16% and 20% of persons with type 2 diabetes have restrictive lung disease, while during the COVID-19 pandemic, lung fibrosis was determined to occur more frequently in individuals with type 2 diabetes than in the general population. [ 37 ]

A study reported that out of 178 adult patients hospitalized with coronavirus disease 2019 (COVID-19), at least one underlying condition was found in 89.3%, the most common being hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). [ 38 ]

According to a report by Stokes et al, out of 287,320 US cases of COVID-19 in which the patient’s underlying health status was known, diabetes was the second most common underlying condition (30%), after cardiovascular disease (32%), which in this study included hypertension. [ 39 , 40 ]

A report by Barrera et al looking at 65 observational studies (15,794 participants) found the overall prevalence of diabetes in patients with COVID-19 to be 12%, with the prevalence being 18% in severe COVID-19. [ 41 , 42 ]

Results from a study by Guo et al suggested that in patients with COVID-19 infection, the increase in inflammatory and coagulation markers is greater in those with type 2 diabetes mellitus than in individuals without diabetes. This may help to indicate why the risk of more severe disease and death from COVID-19 infection is higher in patients with diabetes. [ 43 , 44 ]

Secondary diabetes

Various other types of diabetes, previously called secondary diabetes, are caused by other illnesses or medications. Depending on the primary process involved (eg, destruction of pancreatic beta cells or development of peripheral insulin resistance), these types of diabetes behave similarly to type 1 or type 2 diabetes.

The most common causes of secondary diabetes are as follows:

Diseases of the pancreas that destroy the pancreatic beta cells (eg, hemochromatosis, pancreatitis, cystic fibrosis , pancreatic cancer )

Hormonal syndromes that interfere with insulin secretion (eg, pheochromocytoma)

Hormonal syndromes that cause peripheral insulin resistance (eg, acromegaly, Cushing syndrome, pheochromocytoma)

Drugs (eg, phenytoin, glucocorticoids, estrogens)

Gestational diabetes

Gestational diabetes mellitus is defined as any degree of glucose intolerance with onset or first recognition during pregnancy (see Diabetes Mellitus and Pregnancy ). Gestational diabetes mellitus is a complication of approximately 4% of all pregnancies in the United States. A steady decline in insulin sensitivity as gestation progresses is a normal feature of pregnancy; gestational diabetes mellitus results when maternal insulin secretion cannot increase sufficiently to counteract the decrease in insulin sensitivity.

A study by Ahlqvist et al suggested that type 1 and type 2 diabetes mellitus can actually be divided into five separate types, or clusters, of diabetes. Using six variables to analyze almost 15,000 patients in Sweden and Finland, the investigators came up with the following clusters, the first of which corresponds to type 1 diabetes and the rest of which are subtypes of type 2 diabetes [ 45 , 46 ] :

• Severe autoimmune diabetes (SAID) - Essentially corresponding with type 1 diabetes and latent autoimmune diabetes in adults (LADA), this form is characterized by onset at a young age and patients with a relatively low body mass index (BMI), poor metabolic control, and impaired insulin production; in addition, this cluster is positive for glutamic acid decarboxylase antibodies (GADA)
• Severe insulin-deficient diabetes (SIDD) - This cluster is similar to SAID but is GADA-negative and is characterized by high HbA1c and the greatest risk for diabetic retinopathy among all the clusters
• Severe insulin-resistant diabetes (SIRD) - This cluster is characterized by insulin resistance and patients with a high BMI and the greatest risk for diabetic nephropathy
• Mild obesity-related diabetes (MOD) - Patients in this cluster are younger, have obesity, and are not insulin resistant
• Mild age-related diabetes (MARD) - Patients in this cluster are older, and their metabolic alterations are modest

The investigators maintained that studies in less homogeneous populations are needed to confirm their results but see their report as a “first step towards a more precise, clinically useful stratification” of diabetes. [ 46 ]

The etiology of type 2 diabetes mellitus appears to involve complex interactions between environmental and genetic factors. Presumably, the disease develops when a diabetogenic lifestyle (ie, excessive caloric intake, inadequate caloric expenditure, obesity) is superimposed on a susceptible genotype.

The body mass index (BMI) at which excess weight increases risk for diabetes varies with different racial groups. For example, compared with persons of European ancestry, persons of Asian ancestry are at increased risk for diabetes at lower levels of overweight. [ 47 ] Hypertension and prehypertension are associated with a greater risk of developing diabetes in Whites than in African Americans. [ 48 ]

In addition, an in utero environment resulting in low birth weight may predispose some individuals to develop type 2 diabetes mellitus. [ 49 , 50 , 51 ] Infant weight velocity has a small, indirect effect on adult insulin resistance, and this is primarily mediated through its effect on BMI and waist circumference. [ 52 ]

Approximately 90% of individuals with type 2 diabetes mellitus are overweight or have obesity. [ 53 ] However, a large, population-based, prospective study has shown that an energy-dense diet may be a risk factor for the development of diabetes that is independent of baseline obesity. [ 54 ]

A study by Cameron et al indicated that in the United States between 2013 and 2016, obesity was responsible for the development of new-onset diabetes in 41% of adults. The highest attributable rate of obesity-related diabetes was among non-Hispanic White women (53%); non-Hispanic Black men demonstrated the lowest rate, with the attributable fraction being 30%. [ 55 , 56 ]

Some studies suggest that environmental pollutants may play a role in the development and progression of type 2 diabetes mellitus. [ 57 ] A structured and planned platform is needed to fully explore the diabetes-inducing potential of environmental pollutants.

Secondary diabetes may occur in patients taking glucocorticoids or when patients have conditions that antagonize the actions of insulin (eg, Cushing syndrome, acromegaly, pheochromocytoma).

A study by Pauza et al suggested that glucagonlike peptide–1 (GLP-1) is associated with the link between diabetes and hypertension. The investigators found that GLP-1 receptors are expressed on the carotid body and, working with rats, determined that reduced expression of these receptors “is linked to sympathetic hyperactivity in rats with cardiometabolic disease.” Thus, the research indicates that GLP-1 not only plays its known part in glucose control (by stimulating insulin release) but is associated with blood pressure control as well. [ 58 , 59 ]

Major risk factors

The major risk factors for type 2 diabetes mellitus are the following:

Age greater than 45 years (though, as noted above, type 2 diabetes mellitus is occurring with increasing frequency in young individuals)

Weight greater than 120% of desirable body weight

Family history of type 2 diabetes in a first-degree relative (eg, parent or sibling)

Hispanic, Native American, African American, Asian American, or Pacific Islander descent

History of previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)

Hypertension (130/80 mm Hg or above) or dyslipidemia (HDL cholesterol level < 40 mg/dL or triglyceride level >150 mg/dL)

History of gestational diabetes mellitus or of delivering a baby with a birth weight of over 9 lb

Polycystic ovarian syndrome (which results in insulin resistance)

Genetic influences

The genetics of type 2 diabetes are complex and not completely understood. Evidence supports the involvement of multiple genes in pancreatic beta-cell failure and insulin resistance.

Genome-wide association studies have identified dozens of common genetic variants associated with increased risk for type 2 diabetes. [ 19 ] Of the variants thus far discovered, the one with the strongest effect on susceptibility is the transcription factor 7–like 2 ( TCF7L2 ) gene. (For more information, see Type 2 Diabetes and TCF7L2 .)

Identified genetic variants account for only about 10% of the heritable component of most type 2 diabetes. [ 19 ] An international research consortium found that use of a 40-SNP genetic risk score improves the ability to make an approximate 8-year risk prediction for diabetes beyond that which is achievable when only common clinical diabetes risk factors are used. Moreover, the predictive ability is better in younger persons (in whom early preventive strategies could delay diabetes onset) than in those older than 50 years. [ 60 ]

Some forms of diabetes have a clear association with genetic defects. The syndrome historically known as maturity onset diabetes of youth (MODY), which is now understood to be a variety of defects in beta-cell function, accounts for 2-5% of individuals with type 2 diabetes who present at a young age and have mild disease. The trait is autosomal dominant and can be screened for through commercial laboratories.

To date, 11 MODY subtypes have been identified, involving mutations in the following genes [ 61 , 62 ] :

HNF-4-alpha

Glucokinase gene

HNF-1-alpha

KLF11 [ 63 ]

PAX4 [ 65 ]

Most of the MODY subtypes are associated with diabetes only; however, MODY type 5 is known to be associated with renal cysts, [ 67 ] and MODY type 8 is associated with exocrine pancreatic dysfunction. [ 64 ]

A number of variants in mitochondrial deoxyribonucleic acid (DNA) have been proposed as an etiologic factor for a small percentage of patients with type 2 diabetes. Two specific point mutations and some deletions and duplications in the mitochondrial genome can cause type 2 diabetes and sensorineural hearing loss. [ 68 ]

Diabetes can also be a finding in more severe mitochondrial disorders such as Kearns-Sayre syndrome and mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode (MELAS). Mitochondrial forms of diabetes mellitus should be considered when diabetes occurs in conjunction with hearing loss, myopathy, seizure disorder, strokelike episodes, retinitis pigmentosa, external ophthalmoplegia, or cataracts. These findings are of particular significance if there is evidence of maternal inheritance.

A meta-analysis of two studies indicated that a genetically associated low birth weight increases an individual’s risk for developing type 2 diabetes. The report found that for each one-point increase in an individual’s genetic risk score for low birth weight, the type 2 diabetes risk rose by 6%. [ 69 , 70 ]

Accumulating evidence suggests that depression is a significant risk factor for developing type 2 diabetes. Pan et al found that the relative risk was 1.17 in women with depressed mood and 1.25 in women using antidepressants. [ 71 ] Antidepressant use may be a marker of more severe, chronic, or recurrent depression, or antidepressant use itself may increase diabetes risk, possibly by altering glucose homeostasis or promoting weight gain.

In turn, type 2 diabetes has been identified as a risk factor for the development of depression. Depressive symptoms and major depressive disorder are twice as prevalent in patients with type 2 diabetes as in the general population. [ 72 ]

Schizophrenia

Schizophrenia has been linked to the risk for type 2 diabetes. Dysfunctional signaling involving protein kinase B (Akt) is a possible mechanism for schizophrenia; moreover, acquired Akt defects are associated with impaired regulation of blood glucose and diabetes, which is overrepresented in first-episode, medication-naive patients with schizophrenia. [ 73 ] In addition, second-generation antipsychotics are associated with greater risk for type-2 diabetes.

Preeclampsia and gestational hypertension

A population-based, retrospective cohort study of 1,010,068 pregnant women examined the association between preeclampsia and gestational hypertension during pregnancy and the risk of developing diabetes post partum. Results showed the incidence rate of diabetes per 1000 person-years was 6.47 for women with preeclampsia and 5.26 for those with gestational hypertension, compared with 2.81 in women with neither condition. Risk was further elevated in women with preeclampsia or gestational hypertension comorbid with gestational diabetes. [ 74 ]

Evidence exists that coronavirus disease 2019 (COVID-19) may actually lead to the development of type 1 and type 2 diabetes. One theory is that diabetes arises when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, binds “to angiotensin-converting enzyme 2 (ACE2) receptors in key metabolic organs and tissues, including pancreatic beta cells and kidneys.” The CoviDiab registry was established by an international group of diabetes researchers to gather data on COVID-19–related diabetes. [ 75 ]

A report by Xie and Al-Aly found that among study patients who had survived the first 30 days of COVID-19, the risk for diabetes at 1 year was increased by about 40%. More specifically, the hazard ratios (HRs) for diabetes at 1 year among patients who, during the acute infection, were not hospitalized, were hospitalized, or were admitted to intensive care were 1.25, 2.73, and 3.76, respectively. The investigators stated that diabetes "should be considered as a facet of the multifaceted long COVID syndrome." [ 76 , 77 ]

A study by Tang et al detected SARS-CoV-2 antigen in pancreatic beta cells, as taken from autopsy samples from individuals who had had COVID-19. The research indicated that insulin expression decreases in SARS-CoV-2–infected beta cells, with these cells possibly undergoing transdifferentiation. [ 78 ] A study by Wu et al also indicated that infected beta cells secrete less insulin, with the investigators finding evidence that SARS-CoV-2 can induce beta-cell apoptosis. [ 79 ]

A study from the US Centers for Disease Control and Prevention (CDC) indicates that SARS-CoV-2 infection increases the likelihood of diabetes developing in children under age 18 years, more than 30 days post infection. The investigators, using two US health claims databases, reported that pediatric patients with COVID-19 in the HealthVerity database were 31% percent more likely than other youth to receive a new diabetes diagnosis, while those in the IQVIA database were 166% more likely. The study could not specify the type or types of diabetes specifically related to COVID-19, with the report saying that the disease could be causing both type 1 and type 2 diabetes but through differing mechanisms. The researchers suggested, however, that COVID-19 may induce diabetes by directly attacking pancreatic cells that express ACE2 receptors, that it may give rise to diabetes “through stress hyperglycemia resulting from the cytokine storm and alterations in glucose metabolism caused by infection,” or that COVID-19 may cause diabetes via the conversion of prediabetes to diabetes. Whether the diabetes is transient or chronic was also unknown. [ 80 , 81 ]

However, a study by Cromer et al looked at adult patients with newly diagnosed diabetes mellitus at the time of hospital admission for COVID-19, finding that a number of them subsequently regressed to a state of normoglycemia or prediabetes. The investigators reported that out of 64 survivors in the study with newly diagnosed diabetes (62 of whom had type 2 diabetes), 26 (40.6%) were known to undergo such regression (median 323-day follow-up). [ 82 ]

Occurrence in the United States

According to the CDC's National Diabetes Statistics Report, the crude prevalence of diabetes in the adult US population is 14.7%. It was estimated that 11.3% of the adult population have actually been diagnosed, while 3.4% of adults have undiagnosed diabetes. The prevalence of diabetes rises with age, reaching 29.2% in persons aged 65 years or older. Data employed in the report were drawn from 2017-2020. [ 83 , 84 ]

Prediabetes, as defined by the American Diabetes Association, is that state in which blood glucose levels are higher than normal but not high enough to be diagnosed as diabetes. It is presumed that most persons with prediabetes will subsequently progress to diabetes. The above-mentioned CDC report found the age-adjusted estimate for the prevalence of prediabetes in the adult US population to be 10.8%. [ 83 , 84 ]

A study by Andes et al using a cross-sectional analysis of the National Health and Nutrition Examination Survey (2005-2016) indicated that in the United States, prediabetes exists in approximately 1 out of 5 adolescents and 1 out of 4 young adults. [ 85 , 86 ]

However, a study by Liu et al reported a higher incidence of prediabetes in young people, revealing that in the United States by 2018, approximately 28% of individuals between ages 12 and 19 years had the condition; this was up from less than 12% in 1999. A greater prevalence of prediabetes was found in males in this group and in youth with overweight or obesity. [ 87 , 88 ]

In 2014, the CDC reported that about 40% of US adults will develop diabetes, primarily type 2, in their lifetime, and that more than 50% of ethnic minorities will be affected. This is substantially higher than previous estimates. The central reason for the increase is obesity. [ 89 , 90 ]

A study by Ludwig et al found that neighborhoods with high levels of poverty are associated with increases in the incidence of extreme obesity and diabetes. Although the mechanisms behind this association is unclear, further investigation is warranted. [ 91 ]

International occurrence

Type 2 diabetes mellitus is less common in non-Western countries where the diet contains fewer calories and daily caloric expenditure is higher. However, as people in these countries adopt Western lifestyles, weight gain and type 2 diabetes mellitus are becoming virtually epidemic.

The 10th edition of the International Diabetes Federation Diabetes Atlas, published in December 2021, reported that worldwide, 1 in 10 adults has diabetes. The data predicted that there would be a global increase in the number of adults with diabetes from 537 million in 2021 to 786 million by 2045, a 46% rise. Although increases are expected throughout the world, Africa, the Middle East, and Southeast Asia are predicted to have the greatest expansion. [ 92 ]

Race-related demographics

The prevalence of type 2 diabetes mellitus varies widely among various racial and ethnic groups. The image below shows data for various populations. Type 2 diabetes mellitus is more prevalent among Hispanics, Native Americans, African Americans, and Asians/Pacific Islanders than in non-Hispanic Whites. Indeed, the disease is becoming virtually pandemic in some groups of Native Americans and Hispanic people. The risk of retinopathy and nephropathy appears to be greater in Blacks, Native Americans, and Hispanics.

In a study by Selvin et al, differences between Blacks and Whites were noted in many glycemic markers and not just the hemoglobin A1c (HbA1c) level. [ 93 ] This suggests real differences in glycemia, rather than in the hemoglobin glycation process or erythrocyte turnover, between Blacks and Whites.

Age-related demographics

Type 2 diabetes mellitus occurs most commonly in adults aged 40 years or older, and the prevalence of the disease increases with advancing age. Indeed, the aging of the population is one reason that type 2 diabetes mellitus is becoming increasingly common. Virtually all cases of diabetes mellitus in older individuals are type 2.

In addition, however, the incidence of type 2 diabetes is increasing more rapidly in adolescents and young adults than in other age groups. The disease is being recognized increasingly in younger persons, particularly in highly susceptible racial and ethnic groups and the obese. In some areas, more type 2 than type 1 diabetes mellitus is being diagnosed in prepubertal children, teenagers, and young adults. The prevalence of diabetes mellitus by age is shown in the image below.

The prognosis in patients with diabetes mellitus is strongly influenced by the degree of control of their disease. Chronic hyperglycemia is associated with an increased risk of microvascular complications, as shown in the Diabetes Control and Complications Trial (DCCT) in individuals with type 1 diabetes [ 94 , 95 ] and the United Kingdom Prospective Diabetes Study (UKPDS) in people with type 2 diabetes. [ 96 ]

Reversion to normal glucose regulation during attempts to prevent progression of pre-diabetes to frank diabetes is a good indicator of slowing disease progression, and it is associated with a better prognosis. [ 97 ]

Prognosis in intensive therapy

In the UKPDS, more than 5000 patients with type 2 diabetes were followed up for up to 15 years. Those in the intensely treated group had a significantly lower rate of progression of microvascular complications than did patients receiving standard care. Rates of macrovascular disease were not altered except in the metformin-monotherapy arm in obese individuals, in which the risk of myocardial infarction was significantly decreased.

In the 10-year follow-up to the UKPDS, patients in the previously intensively treated group demonstrated a continued reduction in microvascular and all-cause mortality, as well as in cardiovascular events, despite early loss of differences in glycated hemoglobin levels between the intensive-therapy and conventional-therapy groups. [ 98 ] The total follow-up was 20 years, half while in the study and half after the study ended.

Other, shorter studies, such as Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Affairs Diabetes Trial (VADT), showed no improvement in cardiovascular disease and death with tight control (lower targets than in the UKPDS). [ 99 , 100 , 101 ]

In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, increased mortality was noted among the poorly-controlled patients in the intensive glycemic arm; indeed there was a 66% increase in mortality for each 1% increase in HbA1c; the best outcome occurred among patients who achieved the target of an HbA1c of less than 6%. The excess mortality between the intensive and conventional glycemic arms occurred for A1c above 7%.

Differences between the patient populations in these studies and the UKPDS may account for some of the differences in outcome. The patients in these 3 studies had established diabetes and had a prior cardiovascular disease event or were at high risk for a cardiovascular disease event, whereas patients in the UKPDS study were younger, with new-onset diabetes and low rates of cardiovascular disease.

Early, intensive, multifactorial (blood pressure, cholesterol) management in patients with type 2 diabetes mellitus was associated with a small, nonsignificant reduction in the incidence of cardiovascular disease events and death in a multinational European study. [ 102 ] The 3057 patients in this study had diabetes detected by screening and were randomized to receive either standard diabetes care or intensive management of hyperglycemia (target HbA1c < 7.0%), blood pressure, and cholesterol levels.

The benefits of intensive intervention were demonstrated in the Steno-2 study in Denmark, which included 160 patients with type 2 diabetes and persistent microalbuminuria; the mean treatment period was 7.8 years, followed by an observational period for a mean of 5.5 years. Intensive therapy was associated with a lower risk of cardiovascular events, death from cardiovascular causes, progression to end-stage renal disease, and need for retinal photocoagulation. [ 103 ]

A British study indicated that the HbA1c level achieved 3 months after the initial diagnosis of type 2 diabetes mellitus predicts subsequent mortality. In other words, according to the report, aggressive lowering of glucose after diagnosis bodes well for long-term survival. (Intensified diabetes control must be introduced gradually in newly diagnosed patients.) [ 104 ]

Another study, a review of randomized clinical trials, showed that intensive glycemic control reduces the risk of microvascular complications, but at the expense of increased risk of hypoglycemia. All-cause mortality and cardiovascular mortality in the study did not differ significantly with intensive versus conventional glycemic control; however, trials conducted in usual-care settings showed a reduction in the risk of nonfatal myocardial infarction. [ 105 ]

Overall, these studies suggest that tight glycemic control (HbA1c < 7% or lower) is valuable for microvascular and macrovascular disease risk reduction in patients with recent-onset disease, no known cardiovascular diseases, and a longer life expectancy. In patients with known cardiovascular disease, a longer duration of diabetes (15 or more years), and a shorter life expectancy, however, tighter glycemic control is not as beneficial, particularly with regard to cardiovascular disease risk. Episodes of severe hypoglycemia may be particularly harmful in older individuals with poorer glycemic control and existing cardiovascular disease.

A study by Zheng et al indicated that HbA1c levels in persons with diabetes are longitudinally associated with long-term cognitive decline, as found using a mean 4.9 cognitive assessments of diabetes patients over a mean 8.1-year follow-up period. The investigators saw a significant link between each 1 mmol/mol rise in HbA1c and an increased rate of decline in z scores for global cognition, memory, and executive function. Patients in the study had a mean age of 65.6 years. The report cited a need for research into whether optimal glucose control in people with diabetes can affect their cognitive decline rate. [ 106 , 107 ]

Vascular disease considerations

One prospective study with a long follow-up challenges the concept of coronary disease risk equivalency between nondiabetic patients with a first myocardial infarction and patients with type 2 diabetes but without any cardiovascular disease. The study found that patients with type 2 diabetes had a lower long-term cardiovascular risk compared with patients with a first myocardial infarction. Other studies have similarly questioned this risk equivalency. [ 108 ]

Patients with diabetes have a lifelong challenge to achieve and maintain blood glucose levels as close to the reference range as possible. With appropriate glycemic control, the risk of microvascular and neuropathic complications is decreased markedly. In addition, if hypertension and hyperlipidemia are treated aggressively, the risk of macrovascular complications decreases as well.

These benefits are weighed against the risk of hypoglycemia and the short-term costs of providing high-quality preventive care. Studies have shown cost savings due to a reduction in acute diabetes-related complications within 1-3 years after starting effective preventive care. Some studies suggest that broad-based focus on treatment (eg, glycemia, nutrition, exercise, lipids, hypertension, smoking cessation) is much more likely to reduce the burden of excess microvascular and macrovascular events.

Yamasaki et al found that abnormal results on single-photon CT myocardial perfusion imaging in asymptomatic patients with type 2 diabetes indicated a higher risk for cardiovascular events (13%), including cardiac death. Smoking and low glomerular filtration rate were significant contributing factors. [ 109 ] However, an earlier study questioned the merit of routine screening with adenosine-stress radionuclide myocardial perfusion imaging (MPI) in otherwise asymptomatic type 2 diabetic patients (the Detection of Ischemia in Asymptomatic Diabetics [DIAD] study). [ 110 ]

In both diabetic and nondiabetic patients, coronary vasodilator dysfunction is a strong independent predictor of cardiac mortality. In diabetic patients without coronary artery disease, those with impaired coronary flow reserve have event rates similar to those with prior coronary artery disease, while patients with preserved coronary flow reserve have event rates similar to nondiabetic patients. [ 111 ]

Diabetes-associated mortality and morbidity

In 2017, diabetes mellitus was the seventh leading cause of death in the United States. [ 12 ]  In addition, diabetes is a contributing cause of death in many cases, and it is probably underreported as a cause of death. Overall, the death rate among people with diabetes is about twice that of people of similar age but without diabetes. [ 112 ]

Diabetes mellitus causes morbidity and mortality because of its role in the development of cardiovascular, renal, neuropathic, and retinal disease. These complications, particularly cardiovascular disease (approximately 50-75% of medical expenditures), are the major sources of expenses for patients with diabetes mellitus.

Diabetic retinopathy

Diabetes mellitus is the major cause of blindness in adults aged 20-74 years in the United States; diabetic retinopathy accounts for 12,000-24,000 newly blind persons every year. [ 113 ] The National Eye Institute estimates that laser surgery and appropriate follow-up care can reduce the risk of blindness from diabetic retinopathy by 90%. [ 113 ]

End-stage renal disease

Diabetes mellitus, and particularly type 2 diabetes mellitus, is the leading contributor to end-stage renal disease (ESRD) in the United States. [ 113 ] According to the CDC, diabetes accounts for 44% of new cases of ESRD. [ 112 ] In 2008, 48,374 people with diabetes in the United States and Puerto Rico began renal replacement therapy, and 202,290 people with diabetes were on dialysis or had received a kidney transplant. [ 113 ]

Neuropathy and vasculopathy

Diabetes mellitus is the leading cause of nontraumatic lower limb amputations in the United States, with a 15- to 40-fold increase in risk over that of the nondiabetic population. In 2006, about 65,700 nontraumatic lower limb amputations were performed related to neuropathy and vasculopathy. [ 113 ]

Cardiovascular disease

The risk for coronary heart disease (CHD) is 2-4 times greater in patients with diabetes than in individuals without diabetes. Cardiovascular disease is the major source of mortality in patients with type 2 diabetes mellitus. Approximately two thirds of people with diabetes die of heart disease or stroke. Men with diabetes face a 2-fold increased risk for CHD, and women have a 3- to 4-fold increased risk.

Although type 2 diabetes mellitus, both early onset (< 60 y) and late onset (>60 y), is associated with an increased risk of major CHD and mortality, only the early onset type (duration >10 y) appears to be a CHD risk equivalent. [ 114 ]

In patients with type 2 diabetes mellitus, a fasting glucose level of more than 100 mg/dL significantly contributes to the risk of cardiovascular disease and death, independent of other known risk factors. [ 115 ] This is based on a review of 97 prospective studies involving 820,900 patients.

Data from a large population-based study affirms that worsening glycemic control appears to increase the risk of heart failure. [ 116 ]

Adolescents with obesity and obesity-related type 2 diabetes mellitus demonstrate a decrease in diastolic dysfunction. [ 117 ] This suggests that they may be at increased risk of progressing to early heart failure compared with adolescents who are either lean or obese but do not have type 2 diabetes mellitus.

A 2010 Consensus Report from a panel of experts chosen jointly by the American Diabetes Association and the American Cancer Society suggested that people with type 2 diabetes are at an increased risk for many types of cancer. [ 118 ] Patients with diabetes have a higher risk for bladder cancer, particularly those patients who use pioglitazone. [ 119 , 120 ] Age, male gender, neuropathy, and urinary tract infections were associated with this risk.

In a meta-analysis of 20 publications comprising 13,008 cancer patients with concurrent type 2 diabetes, researchers found that patients treated with metformin had better overall and cancer-specific survival than those treated with other types of glucose-lowering agents. [ 121 , 122 ] These improvements were observed across cancer subtypes and geographic locations. Risk reduction was significant among patients with prostate, pancreatic, breast, colorectal and other cancers, but not for those with lung cancer. However, it remains unclear whether metformin can modulate clinical outcomes in cancer patients with diabetes.

A study by López-de-Andrés et al found the incidence of postoperative pneumonia in patients with type 2 diabetes to be 21% higher than in nondiabetic patients, although the risk of inhospital mortality following the development of postoperative pneumonia was no greater in the presence of type 2 diabetes. [ 123 ]

A retrospective study by Chen et al of 136 COVID-19 patients with diabetes (primarily type 2 diabetes) found that older age, elevated C-reactive protein, and insulin use were risk factors for mortality. The adjusted odds ratio (OR) for mortality in insulin use was 3.58. It has been questioned, however, whether insulin itself is a risk factor or if the increased mortality reflected the characteristics of the patients taking it. [ 124 , 125 ]

A study by Bode et al indicated that among patients with COVID-19, the US in-hospital death rate for individuals living with diabetes, patients with an HbA1c of 6.5% or higher, and those with hyperglycemia throughout their stay is 29%, a figure over four times greater than that for patients without diabetes or hyperglycemia. Moreover, the in-hospital death rate for patients with no evidence of preadmission diabetes who develop hyperglycemia while admitted was found to be seven times higher (42%). [ 126 , 127 ]

A whole-population study from the United Kingdom reported that the risk of in-hospital death for patients with COVID-19 was 2.0 times greater for those with type 2 diabetes and 3.5 times higher for individuals with type 1 diabetes. However, patients under age 40 years with either type of diabetes were at extremely low risk for death. [ 128 , 129 ]

A retrospective study by Zhu et al found that among individuals with COVID-19, those who also had type 2 diabetes mellitus had a mortality rate of 7.8% (versus 2.7% for those without diabetes), as well as a higher rate of multiple organ injury. However, the investigators also reported that among the patients with type 2 diabetes, the mortality rate was lower in those who, during hospitalization, had well-controlled blood glucose, that is, patients with a glycemic variability within 3.9 to 10.0 mmol/L, than in those with poorly controlled blood glucose, in which the upper limit of glycemic variability extended beyond 10.0 mmol/L. [ 130 , 131 ]

The aforementioned study by Barrera et al indicated that among COVID-19 patients with diabetes, the unadjusted relative risk for admission to an intensive care unit (ICU) is 1.96, and for mortality, 2.78. [ 41 , 42 ]

Another study from the United Kingdom found that risk factors for mortality in COVID-19 patients with type 1 or type 2 diabetes include male sex, older age, renal impairment, non-White ethnicity, socioeconomic deprivation, and previous stroke and heart failure. Moreover, patients with type 1 or type 2 diabetes had a significantly greater mortality risk with an HbA1c level of 86 mmol/mol or above, compared with persons with an HbA1c level of 48-53 mmol/mol. In addition, an HbA1c of 59 mmol/mol or higher in patients with type 2 diabetes increased the risk as well. The study also found that in both types of diabetes, BMI had a U-shaped relationship with death, the mortality risk being increased in lower BMI and higher BMI but being reduced between these (25.0-29.9 kg/m 2 ). [ 132 , 129 ]

A literature review by Schlesinger et al strengthened the association between severe diabetes and COVID-19–related mortality, finding that among study patients with diabetes, the likelihood of death from COVID-19 was 75% greater in chronic insulin users. The study also indicated that the chance of death from COVID-19 is 50% less in individuals undergoing metformin therapy than in other patients with diabetes. The investigators suggested that the medications themselves did not impact survival but were indicators of the severity of diabetes in each group, with the prognosis being poorer among those with more severe diabetes. [ 133 , 134 ]

A retrospective study by Wang et al indicated that hyperglycemia, even in the absence of diabetes, is an independent predictor of 28-day mortality in patients with COVID-19. The investigators reported that on admission to two hospitals in Wuhan, China, 29.1% of study patients with COVID-19 and no prior diagnosis of diabetes had a fasting blood glucose of at least 7.0 mmol/L. It was believed that the individuals with hyperglycemia included not only persons with undiagnosed diabetes, but also nondiabetic patients with acute stress hyperglycemia. With regard to 28-day mortality, it was determined that the hazard ratio in patients with a fasting blood glucose of 7.0 mmol/L or higher was 2.30. [ 135 , 136 ]

Similarly, another report found that in study patients with COVID-19 who had a blood glucose level of over 6.1 mmol/L, the risk of disease progression was 58% greater, with the mortality risk being 3.22-fold higher. [ 137 ]

A retrospective, multicenter study by Carrasco-Sánchez et al supported these results, indicating that among noncritical patients with COVID-19, the presence of hyperglycemia on hospital admission independently predicts progression to critical status, as well as death, whether or not the patient has diabetes. The in-hospital mortality rate in persons with a blood glucose level of higher than 180 mg/dL was 41.1%, compared with 15.7% for those with a level below 140 mg/dL. Moreover, the need for ventilation and intensive care unit admission were also greater in the presence of hyperglycemia. The report involved over 11,000 patients with confirmed COVID-19, only about 19% of whom had diabetes. [ 138 , 139 ]

In contrast to the above research, a report by Klonoff et al on over 1500 US patients with COVID-19 found no association between hyperglycemia on hospital admission and mortality, in non-ICU patients. However, the in-hospital mortality rate was significantly greater in such patients if they had a blood glucose level above 13.88 mmol/L on the second or third hospital day, compared with those with a level below 7.77 mmol/L. Findings for patients admitted directly to the ICU differed from these, with the investigators determining that mortality was associated with the presence of hyperglycemia on admission but was not significantly linked with a high glucose level on the second hospital day. [ 140 , 141 ]

A study by Sardu et al indicated that in hospitalized patients with COVID-19 and moderately severe pneumonia, those with diabetes and those who are hyperglycemic are at higher risk of severe disease than are normoglycemic patients without diabetes. Moreover, among the patients in the study with hyperglycemia, the risk of severe disease was lower in those who were treated with insulin infusion, providing further evidence of the importance of in-hospital glucose control. [ 125 , 142 ]

A study by Cariou et al reported that in patients with diabetes hospitalized for COVID-19, a positive, independent association was found between higher body mass index (BMI) and risk of tracheal intubation and/or death within 7 days. The median BMI in patients who suffered this outcome was 29.1 kg/m 2 , compared with 28.1 kg/m 2 in those who did not. However, an association was not found between long-term glucose control and 7-day tracheal intubation and/or death. Regarding specific outcome rates, the study, in which 88.5% of the diabetes cases were type 2 diabetes, reported that 20.3% of the patients with diabetes who were hospitalized with COVID-19 underwent tracheal intubation within 7 days, while 10.6% died within this time. [ 143 , 144 ]

A French study, by Wargny et al, indicated that among patients with diabetes who are hospitalized with COVID-19, approximately 20% will die within 28 days. Individuals particularly at risk for mortality over this 4-week period include patients of advanced age, as well as those with a history of microvascular complications (especially those who have had kidney or eye damage), who have dyspnea on admission or inflammatory markers (increased white blood cell [WBC] count, raised C-reactive protein, elevated aspartate transaminase), or who have undergone routine insulin and statin treatment. It should be kept in mind, however, that the data was gathered between March 10 and April 10, 2020, with a statement from Diabetes UK explaining that in people with diabetes, COVID-19–associated mortality has decreased over time as treatment has improved. [ 145 , 146 ]

The Centers for Disease Control and Prevention (CDC) includes type 2 diabetes in the list of conditions that increase the likelihood of severe illness in persons with COVID-19, and type 1 diabetes in the list of conditions that may increase this likelihood. [ 147 ]

Pregnancy outcome

Untreated gestational diabetes mellitus can lead to fetal macrosomia, hypoglycemia, hypocalcemia, and hyperbilirubinemia. In addition, mothers with gestational diabetes mellitus have increased rates of cesarean delivery and chronic hypertension.

Despite advanced age, multiparity, obesity, and social disadvantage, patients with type 2 diabetes were found to have better glycemic control, fewer large-for-gestational-age infants, fewer preterm deliveries, and fewer neonatal care admissions compared with patients with type 1 diabetes. This suggests that better tools are needed to improve glycemic control in patients with type 1 diabetes. [ 148 ] (For more information, see Diabetes Mellitus and Pregnancy .)

No longer is it satisfactory to provide patients who have diabetes with brief instructions and a few pamphlets and expect them to manage their disease adequately. Instead, education of these patients should be an active and concerted effort involving the physician, nutritionist, diabetes educator, and other health professionals. Moreover, diabetes education needs to be a lifetime exercise; believing that it can be accomplished in 1 or 2 encounters is misguided.

A randomized, controlled trial found that for patients with poorly controlled diabetes, individual attention and education is superior to group education. [ 149 ] Similarly, a diabetes education and self-management group program in the UK for newly diagnosed patients failed to yield significant benefits. [ 150 ] Nonphysician health professionals are usually much more proficient at diabetes education and have much more time for this very important activity.

A systematic review suggested that patients with type 2 diabetes who have a baseline HbA1c of greater than 8% may achieve better glycemic control when given individual education rather than usual care. Outside that subgroup, however, the report found no significant difference between usual care and individual education. In addition, comparison of individual education with group education showed equal impact on HbA1c at 12-18 months. [ 151 ]

Patient education is an immensely complex topic, however. The clinical impression of most experts in the field is that there is merit in the provision of careful diabetes education at all stages of the disease.

[Guideline] Diagnosis and classification of diabetes mellitus. Diabetes Care . 2010 Jan. 33 Suppl 1:S62-9. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. Standards of medical care in diabetes--2012. Diabetes Care . 2012 Jan. 35 Suppl 1:S11-63. [QxMD MEDLINE Link] .

U.S. Preventive Services Task Force. Screening for Type 2 Diabetes Mellitus in Adults. Available at http://www.ahrq.gov/clinic/uspstf/uspsdiab.htm .

[Guideline] Tucker ME. Diabetes Care 2022: Screen More, Personalize, Use Technology. Medscape Medical News . 2021 Dec 20. [Full Text] .

[Guideline] American Diabetes Association. Introduction: Standards of Medical Care in Diabetes-2022. Diabetes Care . 2022 Jan 1. 45 (Supplement_1):S1-S2. [QxMD MEDLINE Link] . [Full Text] .

Keller DM. New EASD/ADA Position Paper Shifts Diabetes Treatment Goals. Medscape Medical News. Available at http://www.medscape.com/viewarticle/771989 . Accessed: October 15, 2012.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia . 2012 Jun. 55(6):1577-96. [QxMD MEDLINE Link] .

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care . 2012 Jun. 35(6):1364-79. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. New diabetes guidelines ease systolic blood pressure target. December 20, 2012. Medscape Medical News. Available at http://www.medscape.com/viewarticle/776543 . Accessed: January 8, 2013.

[Guideline] American Diabetes Association Professional Practice Committee. American Diabetes Association clinical practice recommendations: 2013. Diabetes Care . January 2013. 36 (suppl 1):S1-S110. [Full Text] .

Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care . 2003 Jan. 26 Suppl 1:S5-20. [QxMD MEDLINE Link] .

Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. CDC. Available at https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf .

Harrison P. Almost Half the US Population Has Diabetes or Its Precursor. Medscape Medical News . 2017 Jul 19. [Full Text] .

Unger RH, Orci L. Paracrinology of islets and the paracrinopathy of diabetes. Proc Natl Acad Sci U S A . 2010 Sep 14. 107(37):16009-12. [QxMD MEDLINE Link] . [Full Text] .

Philippe MF, Benabadji S, Barbot-Trystram L, Vadrot D, Boitard C, Larger E. Pancreatic volume and endocrine and exocrine functions in patients with diabetes. Pancreas . 2011 Apr. 40(3):359-63. [QxMD MEDLINE Link] .

Bacha F, Lee S, Gungor N, Arslanian SA. From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation. Diabetes Care . 2010 Oct. 33(10):2225-31. [QxMD MEDLINE Link] . [Full Text] .

Hansen KB, Vilsboll T, Bagger JI, Holst JJ, Knop FK. Increased postprandial GIP and glucagon responses, but unaltered GLP-1 response after intervention with steroid hormone, relative physical inactivity, and high-calorie diet in healthy subjects. J Clin Endocrinol Metab . 2011 Feb. 96(2):447-53. [QxMD MEDLINE Link] .

Wheeler E, Barroso I. Genome-wide association studies and type 2 diabetes. Brief Funct Genomics . 2011 Mar. 10(2):52-60. [QxMD MEDLINE Link] .

Billings LK, Florez JC. The genetics of type 2 diabetes: what have we learned from GWAS? Ann N Y Acad Sci. 2010 Nov;1212:59-77. [Full Text] .

Nielsen EM, Hansen L, Carstensen B, Echwald SM, Drivsholm T, Glumer C, et al. The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes . 2003 Feb. 52(2):573-7. [QxMD MEDLINE Link] .

Ukkola O, Sun G, Bouchard C. Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes. Diabetologia . 2001 Dec. 44(12):2231-6. [QxMD MEDLINE Link] .

Lindgren CM, McCarthy MI. Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity. Nat Clin Pract Endocrinol Metab . 2008 Mar. 4(3):156-63. [QxMD MEDLINE Link] .

Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature . 2007 Feb 22. 445(7130):881-5. [QxMD MEDLINE Link] .

Sandhu MS, Weedon MN, Fawcett KA, Wasson J, Debenham SL, Daly A, et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet . 2007 Aug. 39(8):951-3. [QxMD MEDLINE Link] . [Full Text] .

Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet . 2010 Feb. 42(2):142-8. [QxMD MEDLINE Link] . [Full Text] .

Chiefari E, Tanyolac S, Paonessa F, Pullinger CR, Capula C, Iiritano S, et al. Functional variants of the HMGA1 gene and type 2 diabetes mellitus. JAMA . 2011 Mar 2. 305(9):903-12. [QxMD MEDLINE Link] .

Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med . 2011 Apr. 17(4):448-53. [QxMD MEDLINE Link] . [Full Text] .

Testa R, Olivieri F, Sirolla C, Spazzafumo L, Rippo MR, Marra M, et al. Leukocyte telomere length is associated with complications of type 2 diabetes mellitus. Diabet Med . 2011 Nov. 28(11):1388-94. [QxMD MEDLINE Link] .

Krssak M, Winhofer Y, Gobl C, Bischof M, Reiter G, Kautzky-Willer A, et al. Insulin resistance is not associated with myocardial steatosis in women. Diabetologia . 2011 Jul. 54(7):1871-8. [QxMD MEDLINE Link] .

Leiter LA, Lundman P, da Silva PM, Drexel H, Junger C, Gitt AK. Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study. Diabet Med . 2011 Nov. 28(11):1343-51. [QxMD MEDLINE Link] .

Stern MP. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents?. Ann Intern Med . 1996 Jan 1. 124(1 Pt 2):110-6. [QxMD MEDLINE Link] .

Haffner SM, D'Agostino R Jr, Mykkanen L, Tracy R, Howard B, Rewers M, et al. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care . 1999 Apr. 22(4):562-8. [QxMD MEDLINE Link] .

Busko M. Gray-matter atrophy may drive cognitive decline in diabetes. Medscape Medical News . August 22, 2013. [Full Text] .

Moran C, Phan TG, Chen J, et al. Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care . 2013 Aug 12. [QxMD MEDLINE Link] .

Brooks M. Depression accelerates cognitive decline in type 2 diabetes. Medscape Medical News . October 17, 2013. [Full Text] .

Sullivan MD, Katon WJ, Lovato LC, Miller ME, Murray AM, Horowitz KR, et al. Association of Depression With Accelerated Cognitive Decline Among Patients With Type 2 Diabetes in the ACCORD-MIND Trial. JAMA Psychiatry . 2013 Oct 1. 70(10):1041-7. [QxMD MEDLINE Link] .

McCall B. Causal Link Found for Type 2 Diabetes and Lung Complications. Medscape News UK . 2023 Apr 28. [Full Text] .

Garg S, Kim L, Whitaker M, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR . 2020 Apr 8. [Full Text] .

Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep . 2020 Jun 15. [Full Text] .

Franki R. Comorbidities Increase COVID-19 Deaths by Factor of 12. Medscape Medical News . 2020 Jun 17. [Full Text] .

Zoler ML. Cleaner data confirm severe COVID-19 link to diabetes, hypertension. MDedge Cardiology News . 2020 Jul 27. [Full Text] .

Barrera FJ, Shekhar S, Wurth R, et al. Prevalence of Diabetes and Hypertension and their Associated Risks for Poor Outcomes in Covid-19 Patients. J Endocr Soc . 2020 Jul 21. [Full Text] .

King J. Inflammatory markers may explain COVID-19, diabetes dynamic. MDedge . 2020 Apr 15. [Full Text] .

Guo W, Li M, Dong Y, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev . 2020 Mar 31. e3319. [QxMD MEDLINE Link] . [Full Text] .

Ahlqvist E, Storm P, Karajamaki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol . 2018 Mar 1. [QxMD MEDLINE Link] .

Davenport L. Diabetes Consists of Five Types, Not Two, Say Researchers. Medscape Medical News . 2018 Mar 1. [Full Text] .

Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet . 2004 Jan 10. 363(9403):157-63. [QxMD MEDLINE Link] .

Wei GS, Coady SA, Goff DC Jr, et al. Blood pressure and the risk of developing diabetes in African Americans and Whites: ARIC, CARDIA, and the framingham heart study. Diabetes Care . 2011 Apr. 34(4):873-9. [QxMD MEDLINE Link] . [Full Text] .

Dabelea D, Pettitt DJ, Hanson RL, Imperatore G, Bennett PH, Knowler WC. Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care . 1999 Jun. 22(6):944-50. [QxMD MEDLINE Link] .

Yarbrough DE, Barrett-Connor E, Kritz-Silverstein D, Wingard DL. Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study. Diabetes Care . 1998 Oct. 21(10):1652-8. [QxMD MEDLINE Link] .

Li Y, Qi Q, Workalemahu T, Hu FB, Qi L. Birth Weight, Genetic Susceptibility, and Adulthood Risk of Type 2 Diabetes. Diabetes Care . 2012 Aug 24. [QxMD MEDLINE Link] .

Slining MM, Kuzawa CW, Mayer-Davis EJ, Adair LS. Evaluating the indirect effect of infant weight velocity on insulin resistance in young adulthood: a birth cohort study from the Philippines. Am J Epidemiol . 2011 Mar 15. 173(6):640-8. [QxMD MEDLINE Link] . [Full Text] .

American Society for Metabolic an Bariatric Surgery. Type 2 Diabetes and Metabolic Surgery. Available at https://asmbs.org/resources/type-2-diabetes-and-metabolic-surgery-fact-sheet#:~:text=Obesity%20%E2%80%93%20medically%20defined%20as%20a,BMI%20of%20at%20least%2025). . October 2018; Accessed: March 6, 2021.

Wang J, Luben R, Khaw KT, Bingham S, Wareham NJ, Forouhi NG. Dietary energy density predicts the risk of incident type 2 diabetes: the European Prospective Investigation of Cancer (EPIC)-Norfolk Study. Diabetes Care . 2008 Nov. 31(11):2120-5. [QxMD MEDLINE Link] . [Full Text] .

Cameron NA, Petito LC, McCabe M, et al. Quantifying the Sex-Race/Ethnicity-Specific Burden of Obesity on Incident Diabetes Mellitus in the United States, 2001 to 2016: MESA and NHANES. J Am Heart Assoc . 2021 Feb 16. 10 (4):e018799. [QxMD MEDLINE Link] . [Full Text] .

Zoler ML. Obesity Pegged as Diabetes Cause in Almost Half of US Cases. Medscape Medical News . 2021 Feb 18. [Full Text] .

Hectors TL, Vanparys C, van der Ven K, Martens GA, Jorens PG, Van Gaal LF, et al. Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function. Diabetologia . 2011 Jun. 54(6):1273-90. [QxMD MEDLINE Link] .

Pauza AG, Thakkar P, Tasic T, et al. GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition. Circ Res . 2022 Feb 1. CIRCRESAHA121319874. [QxMD MEDLINE Link] . [Full Text] .

Sweet pressure – scientists discover link between high blood pressure and diabetes. University of Bristol. Available at https://www.bristol.ac.uk/news/2022/february/blood-pressure-diabetes.html . February 1, 2022; Accessed: February 2, 2022.

de Miguel-Yanes JM, Shrader P, Pencina MJ, Fox CS, Manning AK, Grant RW, et al. Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms. Diabetes Care . 2011 Jan. 34(1):121-5. [QxMD MEDLINE Link] . [Full Text] .

Winckler W, Weedon MN, Graham RR, McCarroll SA, Purcell S, Almgren P, et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes . 2007 Mar. 56(3):685-93. [QxMD MEDLINE Link] .

Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, Lipkind GM, et al. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes . 2008 Apr. 57(4):1131-5. [QxMD MEDLINE Link] .

Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A . 2005 Mar 29. 102(13):4807-12. [QxMD MEDLINE Link] . [Full Text] .

Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet . 2006 Jan. 38(1):54-62. [QxMD MEDLINE Link] .

Plengvidhya N, Kooptiwut S, Songtawee N, Doi A, Furuta H, Nishi M, et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab . 2007 Jul. 92(7):2821-6. [QxMD MEDLINE Link] .

Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A . 2009 Aug 25. 106(34):14460-5. [QxMD MEDLINE Link] . [Full Text] .

Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet . 2006 Jan. 43(1):84-90. [QxMD MEDLINE Link] . [Full Text] .

van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet . 1992 Aug. 1(5):368-71. [QxMD MEDLINE Link] .

Castellino AM. Genetically Lowered Birth Weight May Cause Type 2 Diabetes. Medscape Medical News . July 4, 2016. [Full Text] .

Wang T, Huang T, Li Y, Zheng Y, Manson JE, Hu FB, et al. Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study. Diabetologia . 2016 Jun 23. [QxMD MEDLINE Link] .

Pan A, Lucas M, Sun Q, van Dam RM, Franco OH, Manson JE, et al. Bidirectional association between depression and type 2 diabetes mellitus in women. Arch Intern Med . 2010 Nov 22. 170(21):1884-91. [QxMD MEDLINE Link] . [Full Text] .

Nouwen A, Winkley K, Twisk J, Lloyd CE, Peyrot M, Ismail K, et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia . 2010 Dec. 53(12):2480-6. [QxMD MEDLINE Link] . [Full Text] .

Siuta MA, Robertson SD, Kocalis H, Saunders C, Gresch PJ, Khatri V, et al. Dysregulation of the norepinephrine transporter sustains cortical hypodopaminergia and schizophrenia-like behaviors in neuronal rictor null mice. PLoS Biol . 2010 Jun 8. 8(6):e1000393. [QxMD MEDLINE Link] . [Full Text] .

Feig DS, Shah BR, Lipscombe LL, Wu CF, Ray JG, Lowe J, et al. Preeclampsia as a risk factor for diabetes: a population-based cohort study. PLoS Med . 2013 Apr. 10(4):e1001425. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. New Global Registry Investigates COVID-19 and New-Onset Diabetes. Medscape Medical News . 2020 Jun 13. [Full Text] .

Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol . 2022 Mar 21. [Full Text] .

Tucker ME. 'Profound Implications': COVID Ups Diabetes Risk 40% a Year Later. Medscape Medical News . 2022 Mar 23. [Full Text] .

Tang X, Uhl S, Zhang T, et al. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab . 2021 May 19. [QxMD MEDLINE Link] . [Full Text] .

Wu CT, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab . 2021 May 18. [QxMD MEDLINE Link] . [Full Text] .

Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged MMWR Morb Mortal Wkly Rep</i>. 2022 Jan 7. 71: [Full Text] .

Tucker ME. COVID-19 Associated With Increased Diabetes Risk in Youth. Medscape Medical News . 2022 Jan 10. [Full Text] .

Cromer SJ, Colling C, Schatoff D, et al. Newly diagnosed diabetes vs. pre-existing diabetes upon admission for COVID-19: Associated factors, short-term outcomes, and long-term glycemic phenotypes. J Diabetes Complications . 2022 Feb 4. 108145. [QxMD MEDLINE Link] . [Full Text] .

Centers for Disease Control and Prevention. National Diabetes Statistics Report. CDC. Available at https://www.cdc.gov/diabetes/data/statistics-report/index.html . Reviewed January 18, 2022; Accessed: January 28, 2022.

Tucker ME. More Than 1 in 10 People in US Have Diabetes, CDC Says. Medscape Medical News . 2022 Jan 26. [Full Text] .

Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence of Prediabetes Among Adolescents and Young Adults in the United States, 2005-2016. JAMA Pediatr . 2019 Dec 2. e194498. [QxMD MEDLINE Link] . [Full Text] .

Dunleavy BP. Prevalence of prediabetes high among U.S. teens, young adults. 2019 Dec 2. Available at https://www.upi.com/Health_News/2019/12/02/Prevalence-of-prediabetes-high-among-US-teens-young-adults/8591575297926/ .

Searing L. Over a quarter of 12-to-19-year-olds have prediabetes, research shows. The Washington Post. Available at https://www.washingtonpost.com/health/2022/04/05/prediabetes-youth/ . April 5, 2022; Accessed: April 6, 2022.

Liu J, Li Y, Zhang D, Yi SS, Liu J. Trends in Prediabetes Among Youths in the US From 1999 Through 2018. JAMA Pediatr . 2022 Mar 28. [QxMD MEDLINE Link] .

Hackethal V. 2 in 5 American Adults Will Develop Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/829833 . Accessed: August 13, 2014.

Gregg EW, Zhuo X, Albright AL, et al. Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985—2011: a modelling study. The Lancet Diabetes & Endocrinology. Available at http://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70161-5/fulltext . Accessed: August 13, 2014.

Ludwig J, Sanbonmatsu L, Gennetian L, Adam E, Duncan GJ, Katz LF, et al. Neighborhoods, obesity, and diabetes--a randomized social experiment. N Engl J Med . 2011 Oct 20. 365(16):1509-19. [QxMD MEDLINE Link] .

Tucker ME. IDF Atlas: 1 in 10 Adults Worldwide Now Has Diabetes. Medscape Medical News . 2021 Dec 7. [Full Text] .

Selvin E, Steffes MW, Ballantyne CM, Hoogeveen RC, Coresh J, Brancati FL. Racial differences in glycemic markers: a cross-sectional analysis of community-based data. Ann Intern Med . 2011 Mar 1. 154(5):303-9. [QxMD MEDLINE Link] . [Full Text] .

Albers JW, Herman WH, Pop-Busui R, Feldman EL, Martin CL, Cleary PA, et al. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes Care . 2010 May. 33(5):1090-6. [QxMD MEDLINE Link] . [Full Text] .

White NH, Sun W, Cleary PA, Tamborlane WV, Danis RP, Hainsworth DP, et al. Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents. Diabetes . 2010 May. 59(5):1244-53. [QxMD MEDLINE Link] . [Full Text] .

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet . 1998 Sep 12. 352(9131):837-53. [QxMD MEDLINE Link] .

Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet . 2012 Jun 16. 379(9833):2243-51. [QxMD MEDLINE Link] .

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med . 2008 Oct 9. 359(15):1577-89. [QxMD MEDLINE Link] .

Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med . 2008 Jun 12. 358(24):2630-3. [QxMD MEDLINE Link] .

Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol . 2009 Jan 20. 53(3):298-304. [QxMD MEDLINE Link] .

Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med . 2009 Jan 8. 360(2):129-39. [QxMD MEDLINE Link] .

Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbek A, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet . 2011 Jul 9. 378(9786):156-67. [QxMD MEDLINE Link] . [Full Text] .

Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med . 2008 Feb 7. 358(6):580-91. [QxMD MEDLINE Link] .

Kerr D, Partridge H, Knott J, Thomas PW. HbA1c 3 months after diagnosis predicts premature mortality in patients with new onset type 2 diabetes. Diabet Med . 2011 Dec. 28(12):1520-4. [QxMD MEDLINE Link] .

Gruss C, Gutierrez C, Burhans WC, DePamphilis ML, Koller T, Sogo JM. Nucleosome assembly in mammalian cell extracts before and after DNA replication. EMBO J . 1990 Sep. 9(9):2911-22. [QxMD MEDLINE Link] . [Full Text] .

Zheng F, Yan L, Yang Z, Zhong B, Xie W. HbA 1c , diabetes and cognitive decline: the English Longitudinal Study of Ageing. Diabetologia . 2018 Jan 25. [QxMD MEDLINE Link] . [Full Text] .

Melville NA. HbA1c Levels in Diabetes Linked to Cognitive Decline. Medscape Medical News . 2018 Jan 30. [Full Text] .

Cano JF, Baena-Diez JM, Franch J, Vila J, Tello S, Sala J, et al. Long-term cardiovascular risk in type 2 diabetic compared with nondiabetic first acute myocardial infarction patients: a population-based cohort study in southern Europe. Diabetes Care . 2010 Sep. 33(9):2004-9. [QxMD MEDLINE Link] . [Full Text] .

Yamasaki Y, Nakajima K, Kusuoka H, Izumi T, Kashiwagi A, Kawamori R, et al. Prognostic value of gated myocardial perfusion imaging for asymptomatic patients with type 2 diabetes: the J-ACCESS 2 investigation. Diabetes Care . 2010 Nov. 33(11):2320-6. [QxMD MEDLINE Link] . [Full Text] .

Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA . 2009 Apr 15. 301(15):1547-55. [QxMD MEDLINE Link] . [Full Text] .

Murthy VL, Naya M, Foster CR, Gaber M, Hainer J, Klein J, et al. Association Between Coronary Vascular Dysfunction and Cardiac Mortality in Patients with and without Diabetes Mellitus. Circulation . 2012 Aug 23. [QxMD MEDLINE Link] .

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf . Accessed: January 5, 2012.

National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics, 2011. National Diabetes Information Clearinghouse. Available at http://diabetes.niddk.nih.gov/dm/pubs/statistics/ . Accessed: January 5, 2012.

Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N. Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors. Arch Intern Med . 2011 Mar 14. 171(5):404-10. [QxMD MEDLINE Link] .

Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med . 2011 Mar 3. 364(9):829-41. [QxMD MEDLINE Link] .

Lind M, Olsson M, Rosengren A, Svensson AM, Bounias I, Gudbjornsdottir S. The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes. Diabetologia . 2012 Aug 16. [QxMD MEDLINE Link] .

Shah AS, Khoury PR, Dolan LM, Ippisch HM, Urbina EM, Daniels SR, et al. The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults. Diabetologia . 2011 Apr. 54(4):722-30. [QxMD MEDLINE Link] .

Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care . 2010 Jul. 33(7):1674-85. [QxMD MEDLINE Link] . [Full Text] .

Tseng CH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia . 2011 Aug. 54(8):2009-15. [QxMD MEDLINE Link] .

Colmers IN, Bowker SL, Majumdar SR, Johnson JA. Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis. CMAJ . 2012 Jul 3. [QxMD MEDLINE Link] .

Yin M, Zhou J, Gorak EJ, Quddus F. Metformin is associated with survival benefit in cancer patients with concurrent type 2 diabetes: a systematic review and meta-analysis. Oncologist . 2013 Nov 20. [QxMD MEDLINE Link] . [Full Text] .

Nelson R. Metformin boosts survival in diabetic cancer patients. Medscape Medical News . November 25, 2013. [Full Text] .

Lopez-de-Andres A, Perez-Farinos N, de Miguel-Diez J, et al. Type 2 diabetes and postoperative pneumonia: An observational, population-based study using the Spanish Hospital Discharge Database, 2001-2015. PLoS One . 2019. 14 (2):e0211230. [QxMD MEDLINE Link] . [Full Text] .

Chen Y, Yang D, Cheng B, et al. Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Diabetes Care . 2020 May 14. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. 'The Story Unfolding Is Worrisome' for Diabetes and COVID-19. Medscape Medical News . 2020 May 26. [Full Text] .

Bode B, Garrett V, Messler J, et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. J Diabetes Sci Technol . 2020. [Full Text] .

Tucker ME. Pay Attention to In-Hospital Glucose to Save Lives in COVID-19. Medscape Medical News . 2020 Apr 20. [Full Text] .

Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol . 2020 Aug 13. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Newly Published Articles Inform on COVID-19 Risk by Diabetes Type. Medscape Medical News . 2020 Aug 17. [Full Text] .

Zhu L, She ZG, Cheng X, et al. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab . 2020 May 1. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Largest Study to Date Links Glucose Control to COVID-19 Outcomes. Medscape Medical News . 2020 May 14. [Full Text] .

Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol . 2020 Aug 13. [QxMD MEDLINE Link] . [Full Text] .

Busko M. Older, Sicker Diabetes Patients Have Worse COVID-19 Prognosis. Medscape Medical News . 2021 Apr 28. [Full Text] .

Schlesinger S, Neuenschwander M, Lang A, et al. Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis. Diabetologia . 2021 Apr 28. [QxMD MEDLINE Link] . [Full Text] .

Wang S, Ma P, Zhang S, et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study. Diabetologia . 2020 Jul 10. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Hyperglycemia predicts COVID-19 death even without diabetes. MDedge Internal Medicine . 2020 Jul 13. [Full Text] .

Wang W, Shen M, Tao Y, et al. Elevated glucose level leads to rapid COVID-19 progression and high fatality. BMC Pulm Med . 2021 Feb 24. 21 (1):64. [QxMD MEDLINE Link] . [Full Text] .

Carrasco-Sanchez FJ, Lopez-Carmona MD, Martinez-Marcos FJ, et al. Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry. Ann Med . 2021 Dec. 53 (1):103-16. [QxMD MEDLINE Link] .

Tucker ME. Blood Glucose on Admission Predicts COVID-19 Severity in All. Medscape Medical News . 2020 Nov 30. [Full Text] .

Klonoff DC, Messler JC, Umpierrez GE, et al. Association Between Achieving Inpatient Glycemic Control and Clinical Outcomes in Hospitalized Patients With COVID-19: A Multicenter, Retrospective Hospital-Based Analysis. Diabetes Care . 2020 Dec 15. [QxMD MEDLINE Link] . [Full Text] .

Harding A. Glycemia in Early COVID-19 Hospitalization Linked to Mortality. Reuters Health Information . 2020 Dec 21. [Full Text] .

Sardu C, D'Onofrio N, Balestrieri ML, et al. Outcomes in Patients With Hyperglycemia Affected by Covid-19: Can We Do More on Glycemic Control?. Diabetes Care . 2020 May 19. [QxMD MEDLINE Link] . [Full Text] .

Cariou B, Hadjadj S, Wargny M, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia . 2020 May 29. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. 10% With Diabetes Hospitalized for COVID-19 Die Within a Week. Medscape Medical News . 2020 Jun 1. [Full Text] .

Wargny M, Potier L, Gourdy P, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study. Diabetologia . 2021 Feb 17. [QxMD MEDLINE Link] . [Full Text] .

Davenport L. 1 in 5 Diabetes Patients Hospitalized With COVID-19 Die in 28 Days. Medscape Medical News . 18 Feb 2021. [Full Text] .

Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): People of Any Age with Underlying Medical Conditions. CDC. Available at https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html . Updated June 25, 2020; Accessed: June 27, 2020.

Murphy HR, Steel SA, Roland JM, Morris D, Ball V, Campbell PJ, et al. Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage. Diabet Med . 2011 Sep. 28(9):1060-7. [QxMD MEDLINE Link] . [Full Text] .

Sperl-Hillen J, Beaton S, Fernandes O, Von Worley A, Vazquez-Benitez G, Parker E, et al. Comparative effectiveness of patient education methods for type 2 diabetes: a randomized controlled trial. Arch Intern Med . 2011 Dec 12. 171(22):2001-10. [QxMD MEDLINE Link] .

Khunti K, Gray LJ, Skinner T, Carey ME, Realf K, Dallosso H, et al. Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care. BMJ . 2012 Apr 26. 344:e2333. [QxMD MEDLINE Link] . [Full Text] .

Duke SA, Colagiuri S, Colagiuri R. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev . 2009 Jan 21. CD005268. [QxMD MEDLINE Link] .

Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care . 1992 Jul. 15(7):815-9. [QxMD MEDLINE Link] .

Nainggolan L. Dawn Phenomenon Affects Half of Type 2 Diabetes Patients. Medscape Medical News . Nov 7 2013. [Full Text] .

Monnier L, Colette C, Dejager S, et al. Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes: is this of concern?. Diabetes Care . 2013 Oct 29. [QxMD MEDLINE Link] .

Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA . 2007 Aug 22. 298(8):902-16. [QxMD MEDLINE Link] .

Frank RN. Diabetic retinopathy. N Engl J Med . 2004 Jan 1. 350(1):48-58. [QxMD MEDLINE Link] .

Ding J, Strachan MW, Fowkes FG, Wong TY, Macgillivray TJ, Patton N, et al. Association of retinal arteriolar dilatation with lower verbal memory: the Edinburgh Type 2 Diabetes Study. Diabetologia . 2011 Jul. 54(7):1653-62. [QxMD MEDLINE Link] .

Hujoel PP, Stott-Miller M. Retinal and gingival hemorrhaging and chronic hyperglycemia. Diabetes Care . 2011 Jan. 34(1):181-3. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Association of Clinical Endocrinologists Statement on the Use of A1C for the Diagnosis of Diabetes. Available at https://www.aace.com/files/AACEpositionA1cfeb2010.pdf . Accessed: May 14 2012.

World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. World Health Organization, Geneva, 2006. Available at http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf .

Brambilla P, La Valle E, Falbo R, Limonta G, Signorini S, Cappellini F, et al. Normal fasting plasma glucose and risk of type 2 diabetes. Diabetes Care . 2011 Jun. 34(6):1372-4. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman MS, et al. Executive summary: guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem . 2011 Jun. 57(6):793-8. [QxMD MEDLINE Link] .

International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care . 2009 Jul. 32(7):1327-34. [QxMD MEDLINE Link] . [Full Text] .

Huang ES, Liu JY, Moffet HH, John PM, Karter AJ. Glycemic control, complications, and death in older diabetic patients: the diabetes and aging study. Diabetes Care . 2011 Jun. 34(6):1329-36. [QxMD MEDLINE Link] . [Full Text] .

Wang W, Lee ET, Howard BV, Fabsitz RR, Devereux RB, Welty TK. Fasting plasma glucose and hemoglobin A1c in identifying and predicting diabetes: the strong heart study. Diabetes Care . 2011 Feb. 34(2):363-8. [QxMD MEDLINE Link] . [Full Text] .

Brooks M. Hemoglobin A1c misses many cases of diabetes. Medscape . 2019 Mar 28. [Full Text] .

Nowicka P, Santoro N, Liu H, Lartaud D, Shaw MM, Goldberg R, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care . 2011 Jun. 34(6):1306-11. [QxMD MEDLINE Link] . [Full Text] .

Vijayakumar P, Nelson RG, Hanson RL, Knowler WC, Sinha M. HbA1c and the Prediction of Type 2 Diabetes in Children and Adults. Diabetes Care . 2017 Jan. 40 (1):16-21. [QxMD MEDLINE Link] . [Full Text] .

Davenport L. HbA1c Predicts Diabetes Risk in Children and Adolescents. Medscape Medical News . 2017 Jan 4. [Full Text] .

Lu ZX, Walker KZ, O'Dea K, Sikaris KA, Shaw JE. A1C for screening and diagnosis of type 2 diabetes in routine clinical practice. Diabetes Care . 2010 Apr. 33(4):817-9. [QxMD MEDLINE Link] . [Full Text] .

Lerner N, Shani M, Vinker S. Predicting type 2 diabetes mellitus using haemoglobin A1c: A community-based historic cohort study. Eur J Gen Pract . 2013 Nov 29. [QxMD MEDLINE Link] .

McCall B. Simple saliva swab and early HbA1c test predict diabetes. Medscape Medical News . February 11, 2014. [Full Text] .

Gerstein HC, Islam S, Anand S, Almahmeed W, Damasceno A, Dans A, et al. Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study. Diabetologia . 2010 Dec. 53(12):2509-17. [QxMD MEDLINE Link] .

Suzuki S, Koga M, Amamiya S, Nakao A, Wada K, Okuhara K, et al. Glycated albumin but not HbA1c reflects glycaemic control in patients with neonatal diabetes mellitus. Diabetologia . 2011 Sep. 54(9):2247-53. [QxMD MEDLINE Link] .

Wilson DM, Xing D, Cheng J, Beck RW, Hirsch I, Kollman C, et al. Persistence of individual variations in glycated hemoglobin: analysis of data from the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Trial. Diabetes Care . 2011 Jun. 34(6):1315-7. [QxMD MEDLINE Link] . [Full Text] .

American Diabetes Association. Standards of Medical Care in Diabetes-2015: Abridged for Primary Care Providers. Clinical Diabetes . 2015. 33(2): [Full Text] .

Colayco DC, Niu F, McCombs JS, Cheetham TC. A1C and cardiovascular outcomes in type 2 diabetes: a nested case-control study. Diabetes Care . 2011 Jan. 34(1):77-83. [QxMD MEDLINE Link] . [Full Text] .

Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med . 2011 Mar 3. 364(9):818-28. [QxMD MEDLINE Link] .

Ng JM, Cooke M, Bhandari S, Atkin SL, Kilpatrick ES. The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes Care . 2010 Nov. 33(11):2310-3. [QxMD MEDLINE Link] . [Full Text] .

Morrison F, Shubina M, Turchin A. Encounter frequency and serum glucose level, blood pressure, and cholesterol level control in patients with diabetes mellitus. Arch Intern Med . 2011 Sep 26. 171(17):1542-50. [QxMD MEDLINE Link] .

Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet . 1998 Sep 12. 352(9131):854-65. [QxMD MEDLINE Link] .

[Guideline] Busko M. HbA1c Below 8% in Diabetes for 'Most' Says ACP, But Others Disagree. Medscape Medical News . 2018 Mar 5. [Full Text] .

[Guideline] Qaseem A, Wilt TJ, Kansagara D, et al. Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians. Ann Intern Med . 2018 Mar 6. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Type 2 Diabetes 'Remission' Is a Reality, Say Major Organizations. Medscape Medical News . 2021 Sep 1. [Full Text] .

Riddle MC, Cefalu WT, Evans PH, et al. Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. J Clin Endocrinol Metab . 2021 Aug 30. [QxMD MEDLINE Link] . [Full Text] .

Alfayez OM, Al Yami MS, Alshibani M, et al. Network meta-analysis of nine large cardiovascular outcome trials of new antidiabetic drugs. Prim Care Diabetes . 2019 Jan 31. [QxMD MEDLINE Link] .

Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res . 2008 Sep. 5(3):157-67. [QxMD MEDLINE Link] .

Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care . 2008 Nov. 31(11):2086-91. [QxMD MEDLINE Link] . [Full Text] .

Sun L, Xie C, Wang G, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med . 2018 Dec. 24 (12):1919-29. [QxMD MEDLINE Link] .

Melville NA. Metformin's Effect in Diabetes Linked to Gut Microbiota Changes. Medscape Medical News . 2018 Nov 29. [Full Text] .

Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA . 1999 Jun 2. 281(21):2005-12. [QxMD MEDLINE Link] .

UKPDS 28: a randomized trial of efficacy of early addition of metformin in sulfonylurea-treated type 2 diabetes. U.K. Prospective Diabetes Study Group. Diabetes Care . 1998 Jan. 21(1):87-92. [QxMD MEDLINE Link] .

Qaseem A, Barry MJ, Humphrey LL, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med . 2017 Jan 3. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. ACP Updates Guidelines for Type 2 Diabetes Care. Medscape Medical News . 2017 Jan 3. [Full Text] .

Vashisht R, Jung K, Schuler A, et al. Association of Hemoglobin A1c Levels With Use of Sulfonylureas, Dipeptidyl Peptidase 4 Inhibitors, and Thiazolidinediones in Patients With Type 2 Diabetes Treated With Metformin: Analysis From the Observational Health Data Sciences and Informatics Initiative. JAMA Net Open . 2018 Aug 24. 1(4): [Full Text] .

Tucker ME. Big Data Confirm Type 2 Diabetes Treatment Approach. Medscape Medical News . 2018 Aug 31. [Full Text] .

Kooy A, de Jager J, Lehert P, Bets D, Wulffele MG, Donker AJ, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med . 2009 Mar 23. 169(6):616-25. [QxMD MEDLINE Link] .

Pradhan AD, Everett BM, Cook NR, Rifai N, Ridker PM. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA . 2009 Sep 16. 302(11):1186-94. [QxMD MEDLINE Link] .

Andersson C, Olesen JB, Hansen PR, Weeke P, Norgaard ML, Jorgensen CH, et al. Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia . 2010 Dec. 53(12):2546-53. [QxMD MEDLINE Link] .

Roussel R, Travert F, Pasquet B, Wilson PW, Smith SC Jr, Goto S, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med . 2010 Nov 22. 170(21):1892-9. [QxMD MEDLINE Link] .

Gross JL, Kramer CK, Leitão CB, Hawkins N, Viana LV, Schaan BD, et al. Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med . 2011 May 17. 154(10):672-9. [QxMD MEDLINE Link] .

Zeller M, Danchin N, Simon D, Vahanian A, Lorgis L, Cottin Y, et al. Impact of type of preadmission sulfonylureas on mortality and cardiovascular outcomes in diabetic patients with acute myocardial infarction. J Clin Endocrinol Metab . 2010 Nov. 95(11):4993-5002. [QxMD MEDLINE Link] .

Bellomo Damato A, Stefanelli G, Laviola L, Giorgino R, Giorgino F. Nateglinide provides tighter glycaemic control than glyburide in patients with Type 2 diabetes with prevalent postprandial hyperglycaemia. Diabet Med . 2011 May. 28(5):560-6. [QxMD MEDLINE Link] .

Retnakaran R, Qi Y, Harris SB, Hanley AJ, Zinman B. Changes over time in glycemic control, insulin sensitivity, and beta-cell function in response to low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance. Diabetes Care . 2011 Jul. 34(7):1601-4. [QxMD MEDLINE Link] . [Full Text] .

DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med . 2011 Mar 24. 364(12):1104-15. [QxMD MEDLINE Link] .

Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet . 2006 Sep 23. 368(9541):1096-105. [QxMD MEDLINE Link] .

Phung OJ, Sood NA, Sill BE, Coleman CI. Oral anti-diabetic drugs for the prevention of Type 2 diabetes. Diabet Med . 2011 Aug. 28(8):948-64. [QxMD MEDLINE Link] .

Charpentier G, Halimi S. Earlier triple therapy with pioglitazone in patients with type 2 diabetes. Diabetes Obes Metab . 2009 Sep. 11(9):844-54. [QxMD MEDLINE Link] .

Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet . 2005 Oct 8. 366(9493):1279-89. [QxMD MEDLINE Link] .

Rennings AJ, Russel FG, Li Y, Deen PM, Masereeuw R, Tack CJ, et al. Preserved response to diuretics in rosiglitazone-treated subjects with insulin resistance: a randomized double-blind placebo-controlled crossover study. Clin Pharmacol Ther . 2011 Apr. 89(4):587-94. [QxMD MEDLINE Link] .

Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CP Jr, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care . 2011 Apr. 34(4):916-22. [QxMD MEDLINE Link] . [Full Text] .

Ferrara A, Lewis JD, Quesenberry CP Jr, Peng T, Strom BL, Van Den Eeden SK, et al. Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care . 2011 Apr. 34(4):923-9. [QxMD MEDLINE Link] . [Full Text] .

Piccinni C, Motola D, Marchesini G, Poluzzi E. Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting. Diabetes Care . 2011 Jun. 34(6):1369-71. [QxMD MEDLINE Link] . [Full Text] .

Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ . 2009 Jan 6. 180(1):32-9. [QxMD MEDLINE Link] . [Full Text] .

US Food and Drug Administration. FDA Drug Safety Communication: Updated Risk Evaluation and Mitigation Strategy (REMS) to Restrict Access to Rosiglitazone-containing Medicines including Avandia, Avandamet, and Avandaryl. Available at http://www.fda.gov/Drugs/DrugSafety/ucm255005.htm . Accessed: January 20, 2012.

Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care . 2009 May. 32(5):762-8. [QxMD MEDLINE Link] . [Full Text] .

Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, et al. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med . 2011 Jan 18. 154(2):103-12. [QxMD MEDLINE Link] .

Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet . 2008 Oct 4. 372(9645):1240-50. [QxMD MEDLINE Link] .

Pencek R, Blickensderfer A, Li Y, Brunell SC, Chen S. Exenatide once weekly for the treatment of type 2 diabetes: effectiveness and tolerability in patient subpopulations. Int J Clin Pract . 2012 Aug 24. [QxMD MEDLINE Link] .

Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab . 2011 May. 96(5):1301-10. [QxMD MEDLINE Link] .

Douglas D. Exenatide More Effective Than Insulin Detemir: Study. Available at http://www.medscape.com/viewarticle/777411 . Accessed: January 15, 2013.

Davies M, Heller S, Sreenan S, Sapin H, Adetunji O, Tahbaz A, et al. Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir: Randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas. Diabetes Care . 2012 Dec 28. [QxMD MEDLINE Link] .

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med . 2016 Jul 28. 375 (4):311-22. [QxMD MEDLINE Link] . [Full Text] .

Tamborlane WV, Barrientos-Perez M, Fainberg U, et al. Liraglutide in Children and Adolescents with Type 2 Diabetes. N Engl J Med . 2019 Apr 28. [QxMD MEDLINE Link] .

US Food and Drug Administration. FDA approves Tanzeum to treat type 2 diabetes [press release]. April 15, 2014. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm393289.htm . Accessed: April 21, 2014.

Busko M. FDA approves weekly injectable diabetes drug: albiglutide. Medscape Medical News . April 15, 2014. [Full Text] .

Douglas D. Albiglutide Long-Acting Option for Diabetes Control. Medscape Medical News. Available at http://www.medscape.com/viewarticle/821700 . Accessed: March 17, 2014.

Pratley RE, Nauck MA, Barnett AH, et al. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol . 2014. Feb 6. [Epub ahead of print].

Tucker M. FDA Approves Once-Weekly Dulaglutide for Type 2 Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/831969 . Accessed: September 26, 2014.

Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care . 2014 Aug. 37(8):2159-67. [QxMD MEDLINE Link] .

Frias JP, Bonora E, Nevarez Ruiz LA, et al. Efficacy and Safety of Dulaglutide 3mg and 4.5mg vs. Dulaglutide 1.5mg: 52-Week Results from AWARD-11 (Abst 357-OR). Presented at the 80th Scientific sessions American of the Diabetes Association. 2020 Jun 12-16. Chicago, IL. Available at https://diabetes.diabetesjournals.org/content/69/Supplement_1/357-OR .

Umpierrez G, Tofe Povedano S, Perez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care . 2014 Aug. 37(8):2168-76. [QxMD MEDLINE Link] .

Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care . 2014 Aug. 37(8):2149-58. [QxMD MEDLINE Link] . [Full Text] .

Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet . 2019 Jul 13. 394 (10193):121-30. [QxMD MEDLINE Link] .

Ahren B, Galstyan G, Gautier JF, et al. Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Diabetes Ther . 2016 Jun 18. [QxMD MEDLINE Link] .

Yabe D, Ambos A, Cariou B, et al. Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications . 2016 May 24. [QxMD MEDLINE Link] . [Full Text] .

Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med . 2015 Dec 3. 373 (23):2247-57. [QxMD MEDLINE Link] . [Full Text] .

Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care . 2012 Jun. 35(6):1225-31. [QxMD MEDLINE Link] . [Full Text] .

Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med . 2016 Nov 10. 375 (19):1834-44. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. FDA Approves CVD Benefit for Once-Weekly Semaglutide. Medscape Medical News . 2020 Jan 17. [Full Text] .

Ozempic (semaglutide SC) [package insert]. Plainsboro, NJ: Novo Nordisk. January 2020. Available at [Full Text] .

Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. JAMA . 2019 Apr 16. 321 (15):1466-80. [QxMD MEDLINE Link] . [Full Text] .

Rodbard HW, Rosenstock J, Canani LH, et al. Oral Semaglutide versus Empagliflozin in Patients with Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care . 2019 Sep 17. [QxMD MEDLINE Link] .

Pratley R, Amod A, Hoff ST, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet . 2019 Jul 6. 394 (10192):39-50. [QxMD MEDLINE Link] .

Rybelsus (semaglutide oral) [package insert]. Plainsboro, NJ: Novo Nordisk. January 2020. Available at [Full Text] .

Frías JP, Davies MJ, Rosenstock J, and the, SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med . 2021 Aug 5. 385 (6):503-515. [QxMD MEDLINE Link] . [Full Text] .

Aschner P, Katzeff HL, Guo H, Sunga S, Williams-Herman D, Kaufman KD, et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab . 2010 Mar. 12(3):252-61. [QxMD MEDLINE Link] .

Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab . 2010 Feb. 12(2):167-77. [QxMD MEDLINE Link] .

Perez-Monteverde A, Seck T, Xu L, Lee MA, Sisk CM, Williams-Herman DE, et al. Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes. Int J Clin Pract . 2011 Sep. 65(9):930-8. [QxMD MEDLINE Link] .

Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med . 2011 Nov. 28(11):1352-61. [QxMD MEDLINE Link] .

Willemen MJ, Mantel-Teeuwisse AK, Straus SM, Meyboom RH, Egberts TC, Leufkens HG. Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionality analysis in the World Health Organization VigiBase. Diabetes Care . 2011 Feb. 34(2):369-74. [QxMD MEDLINE Link] . [Full Text] .

Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care . 2011 Nov. 34(11):2474-6. [QxMD MEDLINE Link] . [Full Text] .

Solerte SB, D'Addio F, Trevisan R, et al. Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study. Diabetes Care . 2020 Sep 29. [QxMD MEDLINE Link] . [Full Text] .

Zoler ML. Fewer Deaths in Hospitalized COVID Diabetes Patients on Sitagliptin. Medscape Medical News . 2020 Oct 1. [Full Text] .

Nainggolan L. FDA approves canagliflozin, a first-in-class diabetes drug. March 29, 2013. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781709 . Accessed: April 2, 2013.

US Food and Drug Administration. FDA approves Invokana to treat type 2 diabetes [press release]. March 29, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm . Accessed: April 2, 2013.

Tucker M. FDA Approves Dapagliflozin (Farxiga) for Type 2 Diabetes Treatment. Medscape Medical News. Available at http://www.medscape.com/viewarticle/818858 . Accessed: January 13, 2014.

FDA News Release. FDA approves Farxiga to treat type 2 diabetes. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm . Accessed: January 13, 2014.

Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol . 2013 Nov. 1(3):208-19. [QxMD MEDLINE Link] .

Ridderstrale M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol . 2014 Jun 16. [QxMD MEDLINE Link] .

Stenlof K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab . 2013 Apr. 15(4):372-82. [QxMD MEDLINE Link] . [Full Text] .

Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open . 2012. 2(5): [QxMD MEDLINE Link] . [Full Text] .

Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med . 2019 Jun 13. 380 (24):2295-306. [QxMD MEDLINE Link] .

Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med . 2012 Mar 20. 156(6):405-15. [QxMD MEDLINE Link] .

Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care . 2011 Sep. 34(9):2015-22. [QxMD MEDLINE Link] . [Full Text] .

Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab . 2011 Oct. 13(10):928-38. [QxMD MEDLINE Link] .

Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care . 2012 Jul. 35(7):1473-8. [QxMD MEDLINE Link] . [Full Text] .

Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med . 2019 Jan 24. 380 (4):347-57. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. FDA Approves Empagliflozin for Reducing CVD Death. Medscape Medical News . 2016 Dec 2. [Full Text] .

Peters AL. 'Incredibly Exciting': Diabetes Drug With CV Benefits. Medscape . 2016 Dec 21. [Full Text] .

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med . 2015 Nov 26. 373 (22):2117-28. [QxMD MEDLINE Link] . [Full Text] .

Terra SG, Focht K, Davies M, et al. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone. Diabetes Obes Metab . 2017 May. 19 (5):721-8. [QxMD MEDLINE Link] .

Rosenstock J, Frias J, Pall D, et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diabetes Obes Metab . 2017 Aug 31. [QxMD MEDLINE Link] .

Dagogo-Jack S, Liu J, Eldor R, et al. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab . 2017 Sep 17. [QxMD MEDLINE Link] . [Full Text] .

Zoler ML. FDA Approves Finerenone (Kerendia) for Slowing CKD in Type 2 Diabetes. Medscape Medical News . 2021 Jul 12. [Full Text] .

Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med . 2020 Dec 3. 383 (23):2219-29. [QxMD MEDLINE Link] . [Full Text] .

US Food and Drug Administration. FDA Approves Drug to Reduce Risk of Serious Kidney and Heart Complications in Adults with Chronic Kidney Disease Associated with Type 2 Diabetes. FDA. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-drug-reduce-risk-serious-kidney-and-heart-complications-adults-chronic-kidney-disease . July 9, 2021; Accessed: July 15, 2021.

de la Pena A, Riddle M, Morrow LA, Jiang HH, Linnebjerg H, Scott A, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care . 2011 Dec. 34(12):2496-501. [QxMD MEDLINE Link] . [Full Text] .

Agency for Healthcare Research and Quality. Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes. AHRQ: Agency for Healthcare Research and Quality. Available at http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=108&pageaction=displayproduct. . Accessed: March 7, 2012.

Blair HA, Keating GM. Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus. Drugs . 2016 Mar. 76 (3):363-74. [QxMD MEDLINE Link] .

Toujeo. US Food and Drug Administration. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206538s006lbl.pdf . Accessed: 2018 Apr 25.

Davies MJ, Gross JL, Ono Y, Sasaki T, Bantwal G, Gall MA, et al. Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial. Diabetes Obes Metab . 2014 Oct. 16 (10):922-30. [QxMD MEDLINE Link] . [Full Text] .

Zinman B, DeVries JH, Bode B, Russell-Jones D, Leiter LA, Moses A, et al. Efficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials. Lancet Diabetes Endocrinol . 2013 Oct. 1 (2):123-31. [QxMD MEDLINE Link] .

Marso SP, McGuire DK, Zinman B, et al. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. N Engl J Med . 2017 Aug 24. 377 (8):723-32. [QxMD MEDLINE Link] . [Full Text] .

Zinman B, Fulcher G, Rao PV, Thomas N, Endahl LA, Johansen T, et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet . 2011 Mar 12. 377(9769):924-31. [QxMD MEDLINE Link] .

Afrezza (insulin inhaled) prescribing information [package insert]. Valencia CA, United States: MannKind Corporation. June 2014. Available at [Full Text] .

Fiasp (insulin aspart) [package insert]. 800 Scudders Mill Road, Plainsboro, NJ 08536: Novo Nordisk Inc. September 2017. Available at [Full Text] .

Nainggolan L. FDA Approves New Fast-Acting Insulin, Fiasp, for Diabetes in Adults. Medscape Medical News . 2017 Sep 29. [Full Text] .

US Food and Drug Administration. Early Communication About Safety of Lantus (Insulin Glargine). [Full Text] .

Suissa S, Azoulay L, Dell'Aniello S, Evans M, Vora J, Pollak M. Long-term effects of insulin glargine on the risk of breast cancer. Diabetologia . 2011 Sep. 54(9):2254-62. [QxMD MEDLINE Link] .

Johnson JA, Bowker SL, Richardson K, Marra CA. Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias. Diabetologia . 2011 Sep. 54(9):2263-71. [QxMD MEDLINE Link] .

Stefansdottir G, Zoungas S, Chalmers J, Kengne AP, Knol MJ, Leufkens HG, et al. Intensive glucose control and risk of cancer in patients with type 2 diabetes. Diabetologia . 2011 Jul. 54(7):1608-14. [QxMD MEDLINE Link] .

Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev . 2011 Oct 5. CD006423. [QxMD MEDLINE Link] .

Handelsman Y, Goldberg RB, Garvey WT, Fonseca VA, Rosenstock J, Jones MR, et al. Colesevelam hydrochloride to treat hypercholesterolemia and improve glycemia in prediabetes: a randomized, prospective study. Endocr Pract . 2010 Jul-Aug. 16(4):617-28. [QxMD MEDLINE Link] .

Rosenstock J, Fonseca VA, Garvey WT, Goldberg RB, Handelsman Y, Abby SL, et al. Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes. Endocr Pract . 2010 Jul-Aug. 16(4):629-40. [QxMD MEDLINE Link] .

Sando KR, Taylor J. Bromocriptine: its place in type 2 diabetes Tx. J Fam Pract . 2011 Nov. 60(11):E1-5. [QxMD MEDLINE Link] .

Gaziano JM, Cincotta AH, O'Connor CM, Ezrokhi M, Rutty D, Ma ZJ, et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care . 2010 Jul. 33(7):1503-8. [QxMD MEDLINE Link] . [Full Text] .

Bolen S, Wilson L, Vassy J, Feldman L, Yeh J, Marinopoulos S, et al. Undefined. 2007 Jul. [QxMD MEDLINE Link] .

Bennett WL, Wilson LM, Bolen S, Maruthur N, Singh S, Chatterjee R, et al. Undefined. 2011 Mar. [QxMD MEDLINE Link] .

Tucker ME. New AACE algorithm addresses all aspects of type 2 diabetes. Medscape Medical News . April 23, 2013. [Full Text] .

[Guideline] Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. AACE Comprehensive Diabetes Management Algorithm 2013. Endocr Pract . 2013 Mar-Apr. 19(2):327-36. [QxMD MEDLINE Link] .

Boule NG, Robert C, Bell GJ, Johnson ST, Bell RC, Lewanczuk RZ, et al. Metformin and exercise in type 2 diabetes: examining treatment modality interactions. Diabetes Care . 2011 Jul. 34(7):1469-74. [QxMD MEDLINE Link] . [Full Text] .

Brooks M. Metformin Cuts Dementia Risk in Type 2 Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/807886 . Accessed: July 23, 2013.

Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract . 2009 Sep-Oct. 15(6):540-59. [QxMD MEDLINE Link] .

Qayyum R, Bolen S, Maruthur N, Feldman L, Wilson LM, Marinopoulos SS, et al. Systematic review: comparative effectiveness and safety of premixed insulin analogues in type 2 diabetes. Ann Intern Med . 2008 Oct 21. 149(8):549-59. [QxMD MEDLINE Link] .

Porcellati F, Lucidi P, Rossetti P, Candeloro P, Andreoli AM, Marzotti S, et al. Differential effects of adiposity on pharmacodynamics of basal insulins NPH, glargine, and detemir in type 2 diabetes mellitus. Diabetes Care . 2011 Dec. 34(12):2521-3. [QxMD MEDLINE Link] . [Full Text] .

Baldwin D, Zander J, Munoz C, Raghu P, Delange-Hudec S, Lee H, et al. A Randomized Trial of Two Weight-Based Doses of Insulin Glargine and Glulisine in Hospitalized Subjects With Type 2 Diabetes and Renal Insufficiency. Diabetes Care . 2012 Jun 14. [QxMD MEDLINE Link] .

Grunberger G, Abelseth JM, Bailey TS, Bode BW, Handelsman Y, Hellman R. Consensus statement by the american association of clinical endocrinologists/american college of endocrinology insulin pump management task force. Endocr Pract . 2014 May 1. 20(5):463-89. [QxMD MEDLINE Link] .

Fritsche A, Larbig M, Owens D, Haring HU. Comparison between a basal-bolus and a premixed insulin regimen in individuals with type 2 diabetes-results of the GINGER study. Diabetes Obes Metab . 2010 Feb. 12(2):115-23. [QxMD MEDLINE Link] .

Siegelaar SE, Kerr L, Jacober SJ, Devries JH. A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study. Diabetes Care . 2011 Apr. 34(4):855-7. [QxMD MEDLINE Link] . [Full Text] .

Chen MJ, Jovanovic A, Taylor R. Utilizing the second-meal effect in type 2 diabetes: practical use of a soya-yogurt snack. Diabetes Care . 2010 Dec. 33(12):2552-4. [QxMD MEDLINE Link] . [Full Text] .

Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK. Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Intern Med . 2007 Sep 18. 147(6):417-22. [QxMD MEDLINE Link] .

Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassaï B, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ . 2011 Jul 26. 343:d4169. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Diabetes in the Elderly Addressed in Consensus Report. Medscape Medical News. October 25, 2012. Accessed November 13, 2012.

Sue Kirkman M, Briscoe VJ, Clark N, et al. Diabetes in Older Adults: A Consensus Report. J Am Geriatr Soc . 2012 Oct 25. [QxMD MEDLINE Link] .

Klonoff DC, Buckingham B, Christiansen JS, Montori VM, Tamborlane WV, Vigersky RA, et al. Continuous glucose monitoring: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab . 2011 Oct. 96(10):2968-79. [QxMD MEDLINE Link] .

Kompala T, Neinstein A. A new era: increasing continuous glucose monitoring use in type 2 diabetes. Am J Manag Care . 2019 Mar. 25 (4 Spec No.):SP123-6. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Noninvasive, Low Cost CGM for Type 2 Diabetes Coming in US and EU. Medscape Medical News . 2020 Dec 2. [Full Text] .

Ahmedani MY, Ul Haque MS, Basit A, Fawwad A, Alvi SF. Ramadan Prospective Diabetes Study: the role of drug dosage and timing alteration, active glucose monitoring and patient education. Diabet Med . 2012 Jan 11. [QxMD MEDLINE Link] .

Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care . 2011 Jul. 34(7):1481-6. [QxMD MEDLINE Link] . [Full Text] .

Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med . 2013 Jul 11. 369(2):145-54. [QxMD MEDLINE Link] . [Full Text] .

Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, Brancati FL, et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care . 2010 Oct. 33(10):2156-63. [QxMD MEDLINE Link] . [Full Text] .

Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet . 2017 Dec 5. [Full Text] .

Nainggolan L. Liquid Diet, Gradual Reintroduction of Food, Prompts Diabetes Remission. Medscape . 2017 Dec 5. [Full Text] .

Esposito K, Maiorino MI, Ciotola M, Di Palo C, Scognamiglio P, Gicchino M, et al. Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial. Ann Intern Med . 2009 Sep 1. 151(5):306-14. [QxMD MEDLINE Link] .

Larsen RN, Mann NJ, Maclean E, Shaw JE. The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: a 12 month randomised controlled trial. Diabetologia . 2011 Apr. 54(4):731-40. [QxMD MEDLINE Link] .

Bassil M, Burgos S, Marliss EB, Morais JA, Chevalier S, Gougeon R. Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus. Diabetologia . 2011 Jul. 54(7):1810-8. [QxMD MEDLINE Link] .

Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, et al. Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study. Ann Intern Med . 2010 Dec 21. 153(12):790-9. [QxMD MEDLINE Link] . [Full Text] .

Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, et al. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care . 2011 Jul. 34(7):1610-6. [QxMD MEDLINE Link] . [Full Text] .

Reeds DN, Patterson BW, Okunade A, Holloszy JO, Polonsky KS, Klein S. Ginseng and ginsenoside Re do not improve ß-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes. Diabetes Care . 2011 May. 34(5):1071-6. [QxMD MEDLINE Link] . [Full Text] .

Clerici C, Nardi E, Battezzati PM, Asciutti S, Castellani D, Corazzi N, et al. Novel soy germ pasta improves endothelial function, blood pressure, and oxidative stress in patients with type 2 diabetes. Diabetes Care . 2011 Sep. 34(9):1946-8. [QxMD MEDLINE Link] . [Full Text] .

n-3 Fatty Acids and Cardiovascular Outcomes in Patients with Dysglycemia. N Engl J Med . 2012 Jun 11. [QxMD MEDLINE Link] .

Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA . 2011 May 4. 305(17):1790-9. [QxMD MEDLINE Link] .

Balducci S, Zanuso S, Nicolucci A, De Feo P, Cavallo S, Cardelli P, et al. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch Intern Med . 2010 Nov 8. 170(20):1794-803. [QxMD MEDLINE Link] .

Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, Kramer K, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA . 2010 Nov 24. 304(20):2253-62. [QxMD MEDLINE Link] . [Full Text] .

Chudyk A, Petrella RJ. Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta-analysis. Diabetes Care . 2011 May. 34(5):1228-37. [QxMD MEDLINE Link] . [Full Text] .

Loimaala A, Groundstroem K, Rinne M, Nenonen A, Huhtala H, Parkkari J, et al. Effect of long-term endurance and strength training on metabolic control and arterial elasticity in patients with type 2 diabetes mellitus. Am J Cardiol . 2009 Apr 1. 103(7):972-7. [QxMD MEDLINE Link] .

Hegde SV, Adhikari P, Kotian S, Pinto VJ, D'Souza S, D'Souza V. Effect of 3-month yoga on oxidative stress in type 2 diabetes with or without complications: a controlled clinical trial. Diabetes Care . 2011 Oct. 34(10):2208-10. [QxMD MEDLINE Link] . [Full Text] .

Dixon JB, Zimmet P, Alberti KG, Rubino F. Bariatric surgery: an IDF statement for obese Type 2 diabetes. Diabet Med . 2011 Jun. 28(6):628-42. [QxMD MEDLINE Link] . [Full Text] .

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med . 2002 Feb 7. 346(6):393-403. [QxMD MEDLINE Link] . [Full Text] .

Davenport L. 'Historic' Guidelines on Role of Bariatric Surgery in Diabetes. Medscape Medical News . May 25, 2016. [Full Text] .

Rubino F, Nathan DM, Eckel RH, et al. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care . 2016 Jun. 39 (6):861-77. [QxMD MEDLINE Link] . [Full Text] .

Courcoulas AP, Patti ME, Hu B, et al. Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes. JAMA . 2024 Feb 27. 331 (8):654-64. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. Bariatric Surgery Tops Usual Care in Type 2 Diabetes. Medscape Medical News . 2024 Feb 27. [Full Text] .

Kashyap SR, Bhatt DL, Wolski K, Watanabe RM, Abdul-Ghani M, Abood B, et al. Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes: Analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care . 2013 Feb 25. [QxMD MEDLINE Link] .

Tucker ME. Bariatric Surgery: Many Can Come Off Insulin Long Term. Medscape . 2017 Nov 6. [Full Text] .

Cigolle CT, Lee PG, Langa KM, Lee YY, Tian Z, Blaum CS. Geriatric conditions develop in middle-aged adults with diabetes. J Gen Intern Med . 2011 Mar. 26(3):272-9. [QxMD MEDLINE Link] . [Full Text] .

Schernhammer E, Hansen J, Rugbjerg K, Wermuth L, Ritz B. Diabetes and the risk of developing Parkinson's disease in Denmark. Diabetes Care . 2011 May. 34(5):1102-8. [QxMD MEDLINE Link] . [Full Text] .

Cereda E, Barichella M, Pedrolli C, Klersy C, Cassani E, Caccialanza R, et al. Diabetes and risk of Parkinson's disease: a systematic review and meta-analysis. Diabetes Care . 2011 Dec. 34(12):2614-23. [QxMD MEDLINE Link] . [Full Text] .

Chen HF, Chen P, Li CY. Risk of malignant neoplasm of the pancreas in relation to diabetes: a population-based study in Taiwan. Diabetes Care . 2011 May. 34(5):1177-9. [QxMD MEDLINE Link] . [Full Text] .

Kanaya AM, Adler N, Moffet HH, Liu J, Schillinger D, Adams A, et al. Heterogeneity of diabetes outcomes among asians and pacific islanders in the US: the diabetes study of northern california (DISTANCE). Diabetes Care . 2011 Apr. 34(4):930-7. [QxMD MEDLINE Link] . [Full Text] .

Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ . 1998 Sep 12. 317(7160):703-13. [QxMD MEDLINE Link] . [Full Text] .

Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet . 1998 Jun 13. 351(9118):1755-62. [QxMD MEDLINE Link] .

[Guideline] Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J. Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline. Ann Intern Med . 2020 Sep 1. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] ElSayed NA, Aleppo G, Aroda VR, et al. Introduction and Methodology: Standards of Care in Diabetes-2023. Diabetes Care . 2023 Jan 1. 46 (Supplement_1):S1-S4. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. ADA Advises New BP, Lipid Targets for People With Diabetes. Medscape Medical News . 2022 Dec 13. [Full Text] .

Anderson RJ, Bahn GD, Moritz TE, Kaufman D, Abraira C, Duckworth W. Blood pressure and cardiovascular disease risk in the Veterans Affairs Diabetes Trial. Diabetes Care . 2011 Jan. 34(1):34-8. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] de Boer IH, Bangalore S, Benetos A, et al. Diabetes and Hypertension: A Position Statement by the American Diabetes Association. Diabetes Care . 2017 Sep. 40 (9):1273-84. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Jenkins K. ADA Updates Recommendations for Managing Hypertension in Diabetes. Medscape . 4 Sep 2017. [Full Text] .

FDA Drug Safety Communication: FDA review of cardiovascular risks for diabetics taking hypertension drug olmesartan not conclusive; label updates required. US Food and Drug Administration. Available at http://www.fda.gov/Drugs/DrugSafety/ucm402323.htm . Accessed: June 29, 2014.

O'Riordan M. No CV risk with olmesartan in diabetics, says FDA review. Medscape Medical News . June 24, 2014. [Full Text] .

Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. N Engl J Med . 2012 Nov 3. [QxMD MEDLINE Link] .

Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care . 2011 Jun. 34(6):1270-6. [QxMD MEDLINE Link] . [Full Text] .

Management of dyslipidemia in adults with diabetes. Diabetes Care . 2000 Jan. 23 Suppl 1:S57-60. [QxMD MEDLINE Link] .

Bell DS, Bakris GL, McGill JB. Comparison of carvedilol and metoprolol on serum lipid concentration in diabetic hypertensive patients. Diabetes Obes Metab . 2009 Mar. 11(3):234-8. [QxMD MEDLINE Link] .

Aspirin therapy in diabetes. Diabetes Care . 2000 Jan. 23 Suppl 1:S61-2. [QxMD MEDLINE Link] .

Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA . 2008 Nov 12. 300(18):2134-41. [QxMD MEDLINE Link] .

Saito Y, Morimoto T, Ogawa H, Nakayama M, Uemura S, Doi N, et al. Low-dose aspirin therapy in patients with type 2 diabetes and reduced glomerular filtration rate: subanalysis from the JPAD trial. Diabetes Care . 2011 Feb. 34(2):280-5. [QxMD MEDLINE Link] . [Full Text] .

Okada S, Morimoto T, Ogawa H, Kanauchi M, Nakayama M, Uemura S, et al. Differential effect of low-dose aspirin for primary prevention of atherosclerotic events in diabetes management: a subanalysis of the JPAD trial. Diabetes Care . 2011 Jun. 34(6):1277-83. [QxMD MEDLINE Link] . [Full Text] .

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet . 1994 Nov 19. 344(8934):1383-9. [QxMD MEDLINE Link] .

MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet . 2002 Jul 6. 360(9326):7-22. [QxMD MEDLINE Link] .

Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet . 2003 Apr 5. 361(9364):1149-58. [QxMD MEDLINE Link] .

Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet . 2004 Aug 21-27. 364(9435):685-96. [QxMD MEDLINE Link] .

Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA . 2011 Jun 22. 305(24):2556-64. [QxMD MEDLINE Link] .

Tucker ME. Statins Up Type 2 Diabetes Risk, Overweight at Greatest Risk. Medscape Medical News . 2019 Mar 13. [Full Text] .

Ahmadizar F, OchoaRosales C, Glisic M, Franco OH, Muka T, Stricker BH. Associations of statin use with glycaemic traits and incident type 2 diabetes. Br J Clin Pharmacol . 2019 Mar 5. [QxMD MEDLINE Link] . [Full Text] .

Tucker ME. ADA endorses ACC/AHA statin guidelines, with caveats. Medscape Medical News. Available at http://www.medscape.com/viewarticle/837138 . Accessed: December 24, 2014.

Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med . 1999 Aug 5. 341(6):410-8. [QxMD MEDLINE Link] .

Frye RL, August P, Brooks MM, Hardison RM, Kelsey SF, MacGregor JM, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med . 2009 Jun 11. 360(24):2503-15. [QxMD MEDLINE Link] . [Full Text] .

Agardh E, Tababat-Khani P. Adopting 3-year screening intervals for sight-threatening retinal vascular lesions in type 2 diabetic subjects without retinopathy. Diabetes Care . 2011 Jun. 34(6):1318-9. [QxMD MEDLINE Link] . [Full Text] .

Sjolie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet . 2008 Oct 18. 372(9647):1385-93. [QxMD MEDLINE Link] .

Oshitari T, Asaumi N, Watanabe M, Kumagai K, Mitamura Y. Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study. Vasc Health Risk Manag . 2008. 4(5):1137-40. [QxMD MEDLINE Link] . [Full Text] .

Food and Drug Administration. FDA Requires Boxed Warning and Risk Mitigation Strategy for Metoclopramide-Containing Drugs. U.S. Food and Drug Administration. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm149533.htm . Accessed: August 4, 2010.

Chou KL, Galetta SL, Liu GT, Volpe NJ, Bennett JL, Asbury AK, et al. Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment. J Neurol Sci . 2004 Apr 15. 219(1-2):35-9. [QxMD MEDLINE Link] .

Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med . 1997 Mar 10. 157(5):545-52. [QxMD MEDLINE Link] .

Sawin CT. Action without benefit. The sliding scale of insulin use. Arch Intern Med . 1997 Mar 10. 157(5):489. [QxMD MEDLINE Link] .

Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA . 2008 Aug 27. 300(8):933-44. [QxMD MEDLINE Link] .

Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med . 2009 Mar 26. 360(13):1283-97. [QxMD MEDLINE Link] .

Van den Berghe G, Wilmer A, Milants I, Wouters PJ, Bouckaert B, Bruyninckx F, et al. Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm. Diabetes . 2006 Nov. 55(11):3151-9. [QxMD MEDLINE Link] .

Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ . 1997 May 24. 314(7093):1512-5. [QxMD MEDLINE Link] . [Full Text] .

Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J . 2005 Apr. 26(7):650-61. [QxMD MEDLINE Link] .

Mellbin LG, Malmberg K, Norhammar A, Wedel H, Ryden L. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia . 2011 Jun. 54(6):1308-17. [QxMD MEDLINE Link] .

Avanzini F, Marelli G, Donzelli W, Busi G, Carbone S, Bellato L, et al. Transition from intravenous to subcutaneous insulin: effectiveness and safety of a standardized protocol and predictors of outcome in patients with acute coronary syndrome. Diabetes Care . 2011 Jul. 34(7):1445-50. [QxMD MEDLINE Link] . [Full Text] .

Vanderwood KK, Hall TO, Harwell TS, Butcher MK, Helgerson SD. Implementing a state-based cardiovascular disease and diabetes prevention program. Diabetes Care . 2010 Dec. 33(12):2543-5. [QxMD MEDLINE Link] . [Full Text] .

Reis JP, Loria CM, Sorlie PD, Park Y, Hollenbeck A, Schatzkin A. Lifestyle factors and risk for new-onset diabetes: a population-based cohort study. Ann Intern Med . 2011 Sep 6. 155(5):292-9. [QxMD MEDLINE Link] .

Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL. Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study. Ann Intern Med . 2010 Jan 5. 152(1):10-7. [QxMD MEDLINE Link] .

Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes Care . 2011 Sep. 34(9):2116-22. [QxMD MEDLINE Link] . [Full Text] .

Ibarrola-Jurado N, Salas-Salvado J, Martinez-Gonzalez MA, Bullo M. Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease. Am J Clin Nutr . 2012 Nov. 96(5):1113-8. [QxMD MEDLINE Link] .

National Diabetes Information Clearinghouse. Insulin Resistance and Pre-diabetes. Available at http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance/#medicines .

Xiang AH, Hodis HN, Kawakubo M, Peters RK, Kjos SL, Marroquin A, et al. Effect of pioglitazone on progression of subclinical atherosclerosis in non-diabetic premenopausal Hispanic women with prior gestational diabetes. Atherosclerosis . 2008 Jul. 199(1):207-14. [QxMD MEDLINE Link] . [Full Text] .

Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, Dagenais G, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med . 2006 Oct 12. 355(15):1551-62. [QxMD MEDLINE Link] .

Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract . 2006 Jan-Feb. 12 Suppl 1:25-30. [QxMD MEDLINE Link] .

[Guideline] Jenkins K. ADA Updates Recommendations for Managing Hypertension in Diabetes. Medscape . 2017 Sep 4. [Full Text] .

[Guideline] de Boer IH, Bangalore S, Benetos A, et al. Diabetes and Hypertension: A Position Statement by the American Diabetes Association. Diabetes Care . 2017 Sep. 40 (9):1273-1284. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association Professional Practice Committee. Summary of Revisions: Standards of Care in Diabetes-2024. Diabetes Care . 2024 Jan 1. 47 (Supplement_1):S5-S10. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Davenport L. ADA Releases Comprehensive Type 2 Diabetes Guidelines for Youth. Medscape Medical News . 2018 Nov 19. [Full Text] .

[Guideline] Davies MJ, D'Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care . 2018 Oct 4. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Ivers NM, Jiang M, Alloo J, et al. Diabetes Canada 2018 clinical practice guidelines: Key messages for family physicians caring for patients living with type 2 diabetes. Can Fam Physician . 2019 Jan. 65 (1):14-24. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab . 2019 May 1. 104 (5):1520-74. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Tucker ME. New Endocrine Society Guidelines Address Diabetes in Older Adults. Medscape Medical News . 2019 Mar 23. [Full Text] .

[Guideline] Busko M. ESC Diabetes and CVD Guideline: 'Unprecedented' New Evidence. Medscape Medical News . 2019 Sep 2. [Full Text] .

[Guideline] Tucker ME. More Guidance on 'Vulnerable Subgroup' With Diabetes and COVID-19. Medscape Medical News . 2020 Apr 28. [Full Text] .

[Guideline] Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol . 2020 Apr 23. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Grunberger G, Sherr J, Allende M, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: The Use of Advanced Technology in the Management of Persons With Diabetes Mellitus. Endocr Pract . 27 (2021):505-37. [Full Text] .

Tucker ME. 'A Better Picture': First AACE Guidelines on Diabetes Technology. Medscape Medical News . 2021 May 31. [Full Text] .

[Guideline] Mannucci E, Candido R, Monache LD, et al. Italian guidelines for the treatment of type 2 diabetes. Acta Diabetol . 2022 May. 59 (5):579-622. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S7-S12. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S13-S27. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 3. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S28-S37. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 4. Lifestyle Management: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S38-S50. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 5. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S51-4. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S55-S64. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 7. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S65-S72. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S73-S85. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S86-S104. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 10. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S105-18. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 11. Older Adults: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S119-25. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 12. Children and Adolescents: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S126-36. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S137-43. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 14. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S144-51. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] American Diabetes Association. 15. Diabetes Advocacy: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S152-3. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Summary of Revisions: Standards of Medical Care in Diabetes-2018 . Diabetes Care . 2018 Jan. 41 (Suppl 1):S4-S6. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Tucker ME. ADA 2018 Standards Address Diabetes Drugs With CV Benefit. Medscape . 2017 Dec 8. [Full Text] .

One adult in ten will have diabetes by 2030. International Diabetes Federation. November 14, 2011. Available at http://www.idf.org/media-events/press-releases/2011/diabetes-atlas-5th-edition .

Tucker M. FDA Approves Inhaled Insulin Afrezza for Diabetes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827539 . Accessed: July 5, 2014.

Tucker M. FDA OKs Xigduo XR, a New Dapagliflozin-Metformin Combo. Medscape Medical News. Available at http://www.medscape.com/viewarticle/834133 . Accessed: November 10, 2014.

[Guideline] Tucker ME. USPSTF: screen everyone 45 and older for abnormal glucose. Medscape Medical News . Oct 6 2014. [Full Text] .

[Guideline] USPSTF. Public comment on draft recommendation statement and draft evidence review: screening for abnormal glucose and type 2 diabetes mellitus. US Preventive Services Task Force. Available at http://www.uspreventiveservicestaskforce.org/Announcements/News/Item/public-comment-on-draft-recommendation-statement-and-draft-evidence-review-screening-for-abnormal-glucose-and-type-2-diabetes-mellitus . Accessed: Oct 14 2014.

• Simplified scheme for the pathophysiology of type 2 diabetes mellitus.
• Prevalence of type 2 diabetes mellitus in various racial and ethnic groups in the United States (2007-2009 data).
• Prevalence of diabetes mellitus type 2 by age in the United States (2007 estimates).
• Possible physical examination findings in patients with type 2 diabetes mellitus.
• Diagnostic criteria (American Diabetes Association) for diabetes mellitus type 2.
• Major findings from the primary glucose study in the United Kingdom Prospective Diabetes Study (UKPDS).
• Results from metformin substudy in the United Kingdom Prospective Diabetes Study (UKPDS).
• Findings from the blood pressure substudy in the United Kingdom Prospective Diabetes Study (UKPDS).
• Laboratory monitoring guidelines for patients with type 2 diabetes mellitus.
• American Diabetes Association guidelines for low-density lipoprotein cholesterol in diabetes mellitus type 2.
• Treatment of type 2 diabetes mellitus.
• Types of insulin. Premixed insulins can be assumed to have a combination of the onset, peak, and duration of the individual components.
• Simplified scheme for using insulin in treating patients with type 2 diabetes mellitus.
• Simplified scheme of idealized blood glucose values and multiple dose insulin therapy in type 2 diabetes mellitus.

Contributor Information and Disclosures

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinology , American College of Physicians , American Diabetes Association , Endocrine Society Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership , American Association for the Advancement of Science , American College of Medical Practice Executives , American College of Physicians , American Diabetes Association , American Federation for Medical Research , American Heart Association , Central Society for Clinical and Translational Research , Endocrine Society , International Society for Clinical Densitometry , Southern Society for Clinical Investigation Disclosure: Nothing to disclose.

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha , American Academy of Emergency Medicine , American College of Chest Physicians , American College of Emergency Physicians , American College of Physicians , American Heart Association , American Thoracic Society , Arkansas Medical Society , New York Academy of Medicine , New York Academy ofSciences ,and Society for Academic Emergency Medicine

William L Isley, MD Senior Associate Consultant, Associate Professor of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic of Rochester

William L Isley, MD is a member of the following medical societies: Alpha Omega Alpha , American College of Physicians , American Diabetes Association , American Federation for Medical Research , Endocrine Society , and Phi Beta Kappa

Kenneth Patrick L Ligaray, MD Fellow, Department of Endocrinology, Diabetes and Metabolism, St Louis University School of Medicine

Kenneth Patrick Ligaray, MD is a member of the following medical societies: American Association of Clinical Endocrinologists and Endocrine Society

Anne L Peters, MD, CDE Director of Clinical Diabetes Programs, Professor, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, Los Angeles County/University of Southern California Medical Center

Anne L Peters, MD, CDE is a member of the following medical societies: American College of Physicians and American Diabetes Association

Disclosure: Amylin Honoraria Speaking and teaching; AstraZeneca Consulting fee Consulting; Lilly Consulting fee Consulting; Takeda Consulting fee Consulting; Bristol Myers Squibb Honoraria Speaking and teaching; NovoNordisk Consulting fee Consulting; Medtronic Minimed Consulting fee Consulting; Dexcom Honoraria Speaking and teaching; Roche Honoraria Speaking and teaching

David S Schade, MD Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center

David S Schade, MD is a member of the following medical societies: American College of Physicians , American Diabetes Association , American Federation for Medical Research , Endocrine Society , New Mexico Medical Society , New York Academy of Sciences , and Society for Experimental Biology and Medicine

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association , American Federation for Medical Research , Central Society for Clinical Research , and Endocrine Society

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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Scott R Votey, MD is a member of the following medical societies: Society for Academic Emergency Medicine

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Understanding Type 2 Diabetes

• What is type 2 diabetes?
• Symptoms of type 2 diabetes
• Risk factors for type 2 diabetes
• Complications of type 2 diabetes
• Prevention of type 2 diabetes
• Outcomes for type 2 diabetes
• Diagnosis of Type 2 Diabetes
• How is type 2 diabetes diagnosed?
• How is type 2 diabetes monitored?
• What problems can occur with type 2 diabetes?
• Importance of diabetes education in managing the disease
• Management and Treatment of Type 2 Diabetes
• Treatment goals for type 2 diabetes
• Medications for type 2 diabetes
• Diet and exercise for type 2 diabetes treatment
• Alternative treatment of type 2 diabetes
• Hypoglycemia
• Tips for type 2 diabetes self-management
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• Animation - Understanding Type 2 Diabetes
• Slide Show - Understanding Type 2 Diabetes
• Expert Video - What is type 2 diabetes?
• Expert Video - Difference between type 1 and type 2 diabetes
• Expert Video - Symptoms of type 2 diabetes
• Expert Video - Risk factors for diabetes
• Expert Video - What is prediabetes?
• Expert Video - What problems can occur with type 2 diabetes?
• Expert Video - Can type 2 diabetes be prevented?
• Expert Video - Can diabetes be cured?

*Please note: This slide show represents a visual interpretation and is not intended to provide, nor substitute as, medical and/or clinical advice.

Type 2 diabetes is a metabolic disorder that causes sugar, in the form of glucose, to accumulate in the blood rather than being used as fuel by the cells in our body.

When we eat, food is broken down by our digestive system into nutrient molecules that are then absorbed through our digestive tract for use by the body.

Foods containing carbohydrates or various sugars are broken down into glucose.

Glucose is an important source of fuel for many organs in our body.

However, to be able to use the glucose for fuel, the glucose molecule must first enter into the cell.

The pancreas produces a hormone called insulin, a chemical messenger essential for the entry of glucose into cells.

As the blood glucose levels rise after a meal, insulin is released into the bloodstream and sets processes in motion to trigger the removal of glucose from the blood to enter into the cells.

In type 2 diabetes, the cells become resistant to insulin and ignore its message to absorb glucose. This is known as insulin resistance.

In addition, in type 2 diabetes, the pancreas is unable to produce the greater amounts of insulin needed to trigger these resistant cells to take in glucose from the bloodstream.

The most noticeable symptom of diabetes is frequent urination and excessive thirst.

Other symptoms include weakness, drowsiness, and blurred vision. These are caused by chemical imbalances in the blood related to high levels of blood glucose.

About one in four people with type 2 diabetes are unaware that they have the disease.

It is important to catch diabetes early.

Over time, high blood glucose damages the blood vessels This can damage the organs that these vessels supply leading to a variety of health complications.

Damage to the small, or micro blood vessels can cause vision problems, including loss of sight, nerve damage, and kidney disease.

Damage to larger, or macro blood vessels can lead to cardiovascular complications such as heart disease, stroke, and poor blood circulation.

Overweight and inactivity are major causes of diabetes.

A family history of diabetes significantly increases your risk of developing the disease.

Certain ethnic populations are also at increased risk of developing type 2 diabetes

Finally, some medications may increase your diabetes risk, specifically corticosteroids, thiazide diuretics, drugs used to treat certain mental illnesses, and some antiretrovirals used to treat HIV infection.

In summary, type 2 diabetes is a metabolic disorder. It causes sugar, in the form of glucose, to accumulate in the blood rather than being used as fuel for the cells in our body.

If not diagnosed and treated in a timely manner type 2 diabetes can lead to many health complications.

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Pathophysiology and Clinical Manifestations

Normal Physiology

The pancreas has two main functions: to secrete enzymes into the digestive tract and to secrete hormones from the alpha and beta cells located on the islets of Langerhans to regulate blood glucose levels. Normally, when food is eaten, glucose floods the body. The beta cells secrete insulin to lower blood glucose levels by signaling different cells in the body to use glucose for energy and to store the remaining glucose in the liver. The alpha cells then secrete glucagon, which signals the liver to release stored glucose. This prevents blood sugar levels from getting too low. Glucagon accomplishes this by stimulating glycogenolysis and gluconeogenesis. Together, the alpha and beta cells regulate blood glucose levels after each meal (khanacademymedicine, 2015). Lastly, while an individual is in the process of eating, the gut releases incretin, which signals the pancreas to secrete insulin to metabolize the glucose that will soon be present in the circulatory system (McCance & Huether, 2014).

Pathophysiology

In an individual who has type 2 diabetes mellitus (T2DM), a dysfunction exists with cells that are normally sensitive to insulin. The main cells that become insulin resistant/insensitive are the liver, skeletal muscles, and adipose tissue. Although many risk factors exist that contribute to the development of T2DM, only those who are genetically predisposed to a beta cell dysfunction will actually go on to develop this chronic disease. There are many mechanisms that contribute to insulin resistance. These include an abnormality with the insulin molecule, high amounts of insulin antagonists, down-regulation of the insulin receptor, decreased or abnormal activation of post-receptor kinases, and alterations in glucose transporter proteins (McCance & Huether, 2014).

Furthermore, obesity is present in 60-80% of those who have this disease process and can lead to insulin resistance in different ways. The first way is through alterations in the production of adipokines, hormones produced in adipose tissue, which leads to leptin resistance and a decreased level of adiponectins. Normally, leptin contributes to feeling sated and adiponectins regulate glucose levels. Secondly, obese individuals have elevated levels of serum free fatty acids and intracellular lipid deposits such as cholesterol and triglycerides.  This can be detrimental because it leads to an interference of intracellular insulin signaling, decreased tissue responses to insulin, alterations in insulin, incretin, and glucagon secretion, and promotes inflammation. Another possible mechanism is the release of inflammatory cytokines from intra-abdominal adipocytes and activated macrophages in other tissues. These cytokines induce insulin resistance and the genesis of fatty liver, atherosclerosis, and dyslipidemia. Obesity can also reduce insulin-stimulated mitochondrial activity. This can result in the triggering of insulin resistance, especially in skeletal muscles and hepatocytes. Lastly, obesity is associated with hyperinsulinemia (a condition where excess insulin is circulating in the blood in relation to the amount of glucose) and decreased insulin receptor density. As a result of hyperinsulinemia, symptoms of T2DM can take a while to manifest (McCance & Huether, 2014).

Eventually, beta-cell dysfunction occurs as a result of a decrease in beta-cell mass. Beta cells are very sensitive to high levels of glucose and free fatty acids, two consequences of obesity, and undergo apoptotic cell death. However, although beta cells are under attack, alpha cells still continue to release glucagon which results in hyperglycemia often seen in type 2 diabetics. Moreover, amylin, another beta-cell hormone, is also decreased in type 2 diabetics. Normally, amylin increases satiety and decreases the release of glucagon from alpha cells. Lastly, hyperinsulinemia and hyperleptinemia, excess leptin in the circulatory system, lead to decreased levels of ghrelin in T2DM. Ghrelin is a peptide produced in the stomach and pancreatic islets. Decreased levels are associated with alterations in insulin secretion, insulin resistance, and obesity (McCance & Huether, 2014).

Clinical Manifestations 

Generally, symptoms can be vague and unalarming, therefore many people go years without diagnosis and treatment. Classic symptoms of T2DM include polyuria, polydipsia, and polyphagia (Berkowitz, 2007). However, fatigue, pruritus, recurrent infections, visual changes, or symptoms of neuropathy (paresthesia or weakness) may be experienced. Uncontrolled T2DM and chronic hyperglycemia can greatly increase the risk of secondary diseases and therefore symptoms of Coronary Artery Disease, Peripheral Artery Disease, and Cardiovascular Disease can be present (McCance & Huether, 2014)

In the history of present illness, Ms. Yazzie stated that she has been feeling “fatigued and weak at times, as well as having symptoms of sinusitis and two back-to-back yeast infections. She recently bought a water bottle because she noticed she was thirsty ‘all the time.’” The reason why Ms. Yazzie has been feeling fatigued and weak is because her skeletal muscle cells and her adipose cells are not effectively utilizing glucose for energy. The receptors on these cells have become unresponsive to insulin, which inhibits glucose from entering into these cells. Additionally, the sinusitis and yeast infections are a result of an increase in the inflammatory response due to elevated levels of inflammatory cytokines in the body. Lastly, the reason why Ms. Yazzie suffers from polydipsia (increased thirst) is due to polyuria (increased urination). When there is an increased amount of glucose in the circulatory system, as is the case with diabetics, the kidney will excrete glucose, resulting in the passive movement of fluids out of the body.

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Insulin for people with type 2 diabetes mellitus

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• Peer review
• Natalie Vanderpant , specialist registrar in diabetes and endocrinology 1 ,
• Emily Ward , cardiometabolic pharmacist 2 ,
• Edward Farrell , general practitioner and diabetes primary care network diabetes lead 3 ,
• Aikaterini Theodoraki , consultant physician in diabetes and endocrinology 4
• 1 Department of diabetes and endocrinology, Imperial College Healthcare NHS Trust, London, UK
• 2 Chelsea and Westminster NHS Foundation Trust, London
• 3 Shirland Medical, Queens Park Health Centre, London
• 4 Department of diabetes and endocrinology, Chelsea and Westminster NHS Foundation Trust, London
• Correspondence to: N Vanderpant natalie.vanderpant{at}nhs.net

What you need to know

Explain the role of the multidisciplinary team in supporting patients who are starting insulin

Basal insulin is the most convenient initial insulin therapy, with an initial starting dose estimated on body weight (0.1-0.2 units/kg/day)

Patients with an elevated HbA 1c who are taking a basal insulin in combination with appropriate oral medication may require a prandial insulin, either in addition to basal insulin or converting to a pre-mixed insulin regimen

Emphasise the importance of blood glucose monitoring to ensure safe use and titration of insulin

A 55 year old woman with type 2 diabetes (T2DM) consults you at her annual diabetes review. Her HbA 1c has increased to 90 mmol/mol (10.4%, target <53 mmol/mol or 7.0%) from 72 mmol/mol (8.7%). Since diagnosis at the age of 31, she has been taking oral diabetes medications including metformin, dapagliflozin, and gliclazide. Her current body mass index (BMI) is 26.0 kg/m 2 . She has expressed apprehension about starting insulin therapy. Following a recent diagnosis of pre-proliferative retinopathy, she is now open to starting insulin therapy. In collaboration with her, you are exploring the option of insulin to optimise her diabetes management.

How often is insulin prescribed for T2DM, and how does it work?

Worldwide, about 537 million adults have type 1 or type 2 diabetes mellitus, representing approximately 10.5% of the world’s adult population. 1 In the UK, around 7% of the population (4.7 million people) have a diagnosis of diabetes, 90% of whom have T2DM. 2 It is estimated that 15% of people with T2DM require insulin, but only half are appropriately treated because of barriers to insulin availability such as regulatory challenges and issues with supply chains and cost. 3

National and international professional guidelines recommend insulin therapy for adults with T2DM when:

Dual therapy with metformin and another oral drug has not continued to control HbA 1c to below the person’s …

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Diabetes Mellitus, Type 2

Sep 04, 2014

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Diabetes Mellitus, Type 2. Presentation By Heather Hawley. Epidemiology.

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Presentation Transcript

Diabetes Mellitus, Type 2 Presentation By Heather Hawley

Epidemiology • “Diabetes mellitus currently afflicts approximately 21 million Americans, 90% to 95% of whom have type 2 diabetes.” (Ding, Eric L., Song, Yiqing, Malik, Vasanti S., and Liu, Simin. “Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis.”JAMA, 295(11): March 15, 2006: 1288 - 1299. http://jama.ama-assn.org.ezproxy.ahsl.arizona.edu/content/vol295/issue11/index.dtl) • “Both the prevalence rate for diabetes and the number of people with diabetes have increased steadily since a national system for ascertaining diagnosed diabetes was established in 1958.”(Kenny, Susan J., Aubert, Ronald E., and Geiss, Linda S. “Prevalence and Incidence of Non-Insulin-Dependent Diabetes”, in Diabetes in America, 2nd Ed., 44. http://diabetes.niddk.nih.gov/dm/pubs/america/pdf/chapter4.pdf.)

Epidemiology, cont. • Incidence and prevalence of diabetes increases with age. • Prevalence: of Americans 60 and over “18.3 percent (8.6 million people) have diabetes.”(CDC, “Frequently Asked Questions”, http://www.cdc.gov/diabetes/faq/research.htm). • Incidence: Americans 65-79 years of age have rates of diabetes more than five times higher (14.9 per 1000 population) than adults less than 45 years of age (2.9 per 1000 population). • Children are increasing likely to be diagnosed.

Epidemiology, cont. • Diabetes is associated with risk factors such as obesity, sedentary lifestyle, ethnicity and gender.

Impact of the disease upon specific minority/ethnic groups • Minority populations disproportionately affected are: American Indians, Asians, Latinos, and African Americans. • “African Americans are 1.6 times more likely to have diabetes than Non-Hispanic Whites, while Native Americans are 2.2 times more likely and Latinos, 1.5.” (American Diabetes Association, “Minorities with Diabetes at Increased Risk for Heart Disease, Stroke”, http://www.diabetes.org/for-media/2005-press-releases/Heart-Month.jsp.)

Impact of the disease upon specific minority/ethnic groups, cont. • Prevalence: “10.8 percent of non-Hispanic blacks, 10.6 percent of Mexican Americans, and 9.0 percent of American Indians have diabetes, compared with 6.2 percent of whites. Certain minorities also have much higher rates of diabetes-related complications and death, in some instances by as much as 50 percent more than the total population.” (AHRQ, “FactSheet: Diabetes Disparities Among Racial and Ethnic Minorities”, http://www.ahrq.gov/research/diabdisp.htm)

Impact of the disease upon specific minority/ethnic groups, cont. • Growing risk among Asian Americans: “prevalence of type 2 diabetes is 2 to 3 times higher among Japanese Americans living in Seattle compared with non-Hispanic whites. The prevalence is 2.5 times higher among Native Hawaiians compared to white residents of Hawaii .” (National Diabetes Education Program. “Diabetes and Asian Americans and Pacific Islanders”, http://www.ndep.nih.gov/diabetes/pubs/FS_AsAm_Eng.pdf)

Impact of the disease upon specific minority/ethnic groups, cont. • Diabetes is one of the top 10 causes of death for all women. • “For African American women, the diabetes death rates are the highest in terms of both underlying cause (49.6 per 100,000) and multiple causes (156.5 per 100,000). American Indian/Alaska Native and Hispanic women have high rates as well. The lowest rates are reported for Asian/Pacific Islander women.” (U.S. Department of Health & Human Services, “Steps to Healthier Women: Diabetes”.).

Impact of the disease upon specific minority/ethnic groups, cont. • For African American women 20 years old and over, the diabetes rate is 11.8%, and with 1 in 4 African American women over the age of 55 having this disease; a rate which is twice the rate of white women. (U.S. Department of Health & Human Services, “Steps to Healthier Women: Diabetes.”) • Among Latino women, 25% have been diagnosed with this disease, “and about 33 percent of deaths among them list diabetes as the underlying cause,” and among American Indian/Alaska Native women there is “three times the risk of being diagnosed with diabetes as whites of similar age.” (U.S. Department of Health & Human Services, “Steps to Healthier Women: Diabetes.”)

Impact of the disease upon specific minority/ethnic groups, cont. • Among American Indian tribes, the Pima Indians have the highest overall risk, especially for complications such as eye disease. (U.S. Department of Health & Human Services, “Steps to Healthier Women: Diabetes.”)

Current clinical treatment • Hypoglycemic pills and/or insulin AND non-drug interventions for “diet modification, weight control and regular exercise.” (Florence and Yeager. “Treatment of Type 2 Diabetes Mellitus.” 2835-44, 2849-50.) • Foot and eye checks are extremely important • “Diabetes is a leading cause of blindness, renal failure, and foot and leg amputations in adults.”(Florence and Yeager. “Treatment of Type 2 Diabetes Mellitus.” 2835-44, 2849-50.) • Cochrane Systematic Reviews: “Group-based training for self-management strategies in people with type 2 diabetes is effective by improving fasting blood glucose levels, glycated haemoglobin and diabetes knowledge and reducing systolic blood pressure levels, body weight and the requirement for diabetes medication.” (Deakin, McShane, Cade, and Williams. “Group based training for self-management strategies in people with type 2 diabetes mellitus.” The Cochrane Database of Systematic Reviews: http://gateway.ut.ovid.com.ezproxy.ahsl.arizona.edu/gw2/ovidweb.cgi.)

Nursing care • Extremely important in behavioral treatment strategy of encouraging healthy lifestyle changes and patient education. • Nurses are patient educators on: managing diabetes, medications, diet and exercise, glucose monitoring and dispelling myths.

Drug therapy • Drug therapy for type 2 diabetes involves pharmacologic agents such as pills and/or insulin to control blood glucose levels and is usually instituted if diet and exercise fails. • Drug therapy typically starts with monotherapy;if monotherapy fails then combined therapy, where a patient takes up to three oral medications, is usually prescribed. • Drug therapy=hypoglycemic agent from one of five classes: sulfonylureas, meglitinides, thiazolidinediones, biguanides, and [alpha]-glucosidase inhibitors.” (Nelson and Palumbo. “Addition of Insulin to Oral Therapy in Patients with Type 2 Diabetes: 257-263.)

Drug therapy, cont. • If the combined drug therapy fails, and the diabetes patient exceeds the ADA guidelines of blood sugar concentration “greater than 7.0%” on an A1C test (a test for average blood glucose control for the past 2 to 3 months) then insulin therapy is usually instituted. (American Diabetes Association, “A1C Test”, http://www.diabetes.org/type-2-diabetes/a1c-test.jsp)

Nutritional therapy • First resort in treating type 2 diabetes is diet modification and an exercise regimen. • No specific “diabetes diet” that is applicable to everyone; diet should be personalized. • Food eaten is closely connected to blood sugar levels. • Controlling carbohydrate consumption integral for managing blood sugar levels because “carbohydrate consumption has the fastest effect on increasing blood glucose.” (Joslin Diabetes Center, “There is no such thing as a ‘Diabetic Diet’”, http://www.joslin.org/managing_your_diabetes_665.asp) • “For most people with diabetes (and those without, too), a healthy diet consists of 40% to 60% of calories from carbohydrates, 20% from protein and 30% or less from fat.”(American Academy of Family Physicians, “Diabetes and Nutrition”, http://familydoctor.org/349.xml).

Nutritional therapy, cont. • Exercise is another very important element of controlling blood glucose levels, because it burns glucose rapidly. • “With a daily low-resistance, high-frequency exercise/activity program lasting 45 to 55 minutes, the control of blood glucose for those with diabetes improves and stabilizes even before weight loss is achieved.”(Cleveland Clinic Health Information Center, “Diet and Exercise: The Keys to Success with Diabetes.”) • Strong evidence that diet and exercise can also delay or prevent type 2 diabetes. (Burnet, Elliott, Quinn, Plaut, Schwartz, and Chin. “Preventing Diabetes in the Clinical Setting.”84.)

Psychological issues • Anger: “Diabetes is the perfect breeding ground for anger”, because people may feel their lives are threatened. People may become angry because they feel diagnosis is unfair (“Why me?”) (American Diabetes Association, “Anger”, http://www.diabetes.org/type-2-diabetes/anger.jsp) • Depression: “several studies suggest that diabetes doubles the risk of depression compared to those without the disorder.” (National Institute of Mental Health, “Depression and Diabetes”, http://www.nimh.nih.gov/publicat/depdiabetes.cfm) • Depression “negatively impacts psychosocial functioning and quality of life”, depressed diabetics “exhibit poor glycemic control, noncompliance with therapy” and in turn have more “diabetic complications” than non depressed diabetics. (Petersen, Timothy; Iosifescu, Dan V.; Papakostas, George I.; Shear, Deborah L.; Fava, Maurizio. “Clinical characteristics of depressed patients with comorbid diabetes mellitus”. International Clinical Psychopharmacology. 21(1): 2006 Jan: 43-7).

Economic issues: costs of the disease From the American Diabetes Association website, the cost of diabetes in America (90-95% of diabetes cases are type 2): • The total annual economic cost of diabetes in 2002 was estimated to be $132 billion. • Direct medical expenditures totaled $92 billion and comprised $23.2 billion for diabetes care, $24.6 billion for chronic diabetes-related complications, and $44.1 billion for excess prevalence of general medical conditions. Indirect costs resulting from lost workdays, restricted activity days, mortality, and permanent disability due to diabetes totaled $40.8 billion. • The per capita annual costs of health care for people with diabetes rose from $10,071 in 1997 to $13,243 in 2002, an increase of more than 30%. In contrast, health care costs for people without diabetes amounted to $2,560 in 2002. • One out of every 10 health care dollars spent in the United States is spent on diabetes and its complications.

Associations/Advocacy Groups From the MedlinePlus website, Diabetes Organizations: • American Diabetes Association: The American Diabetes Association is “The nation's leading nonprofit health organization providing diabetes research, information and advocacy”, whose mission “is to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” • National Diabetes Education Program (National Institute of Diabetes and Digestive and Kidney Diseases) “is a federally funded program sponsored by the U.S. Department of Health and Human Services' National Institutes of Health and the Centers for Disease Control and Prevention and includes over 200 partners at the federal, state, and local levels, working together to reduce the morbidity and mortality associated with diabetes.” • National Diabetes Information Clearinghouse (National Institute of Diabetes and Digestive and Kidney Diseases) “The National Diabetes Information Clearinghouse (NDIC) is an information dissemination service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health (NIH), one of eight health agencies of the Public Health Service, which is under the U.S. Department of Health and Human Services.” Their mission is “to increase knowledge and understanding about diabetes among patients, health care professionals, and the general public.” • National Institute of Diabetes and Digestive and Kidney Diseases “The National Institute of Diabetes and Digestive and Kidney Diseases conducts and supports research on many of the most serious diseases affecting public health….such as diabetes….”

Consumer/Patient Health Information • American Diabetes Association: Provides diabetes information to those with diabetes and their families, healthcare professionals, and the public. • Arizona Health Sciences Library, Diabetes Subject Guide: Provides diabetes patient resources in the following areas: African Americans, American Indians and Alaska Natives, Arizona Resources, Asians and Pacific Islanders, Children and Teens, Diabetes and Pregnancy, Diabetes Insipidus (Type 1), Diet, Eye Problems, Heart Problems, Kidney Problems, Nerve Problems, General Resources and Hispanic Americans. • Cleveland Clinic Health Information Center: Diabetes Mellitus: Provides Diabetes information on in the following areas: Written resources, Calendar of Events, Clinical Trials, Departmental Website, and Interactive resources. • Joslin Diabetes Center: Focuses on diabetes Research, clinical Care, and consumer Education; is affiliated with the Harvard Medical School. • Medline Plus: Diabetes: Provides diabetes information on: Latest News, From the National Institutes of Health, Overviews, Diagnosis/Symptoms, Treatment, Prevention/Screening, Pictures/Diagrams, Health Check Tools, Alternative Therapy, Nutrition, Coping, Disease Management, Specific Conditions, Related Issues, Financial Issues, Newsletters/Print Publications, Clinical Trials, Genetics, Research, Dictionaries/Glossaries, Directories, Organizations, Law and Policy, Statistics, Children, Men, Women, Seniors, Other Languages.

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Risk of chronic kidney disease in patients with a hyperglycemic crisis as the initial presentation of type 2 diabetes

Affiliations.

• 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei City, 104217, Taiwan.
• 2 Department of Medicine, Mackay Medical College, New Taipei City, 252005, Taiwan.
• 3 Management Office for Health Data, China Medical University Hospital, Taichung City, 404328, Taiwan.
• 4 Management Office for Health Data, China Medical University Hospital, Taichung City, 404328, Taiwan. [email protected].
• 5 Department of Health Services Administration, China Medical University College of Public Health, 100 Jingmao Road Section 1, Beitun Dist., Taichung, 406040, Taiwan. [email protected].
• 6 Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, 413305, Taiwan. [email protected].
• 7 International Master Program for Public Health, China Medical University, Taichung, 406040, Taiwan.
• PMID: 39033190
• DOI: 10.1038/s41598-024-67678-3

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan's insurance claims from adults newly diagnosed with type 2 diabetes during 2006-2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018's end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91-2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59-1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33-2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29-2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

Keywords: Chronic kidney disease; Diabetic ketoacidosis; Diabetic kidney disease; Hyperglycemic crisis; Hyperglycemic hyperosmolar state.

© 2024. The Author(s).

PubMed Disclaimer

• Gosmanov, A. R. et al. Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State (Endotext, 2021).
• Misra, S. et al. Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: A population-based study. Lancet Diabetes Endocrinol. 9, 671–680 (2021). - PubMed - PMC - DOI
• Wachtel, T. J., Tetu-Mouradjian, L. M., Goldman, D. L., Ellis, S. E. & O’Sullivan, P. S. Hyperosmolarity and acidosis in diabetes mellitus: A three-year experience in Rhode Island. J. Gen. Intern. Med. 6, 495–502 (1991). - PubMed - DOI
• Fourtner, S. H., Weinzimer, S. A. & Levitt Katz, L. E. Hyperglycemic hyperosmolar non-ketotic syndrome in children with type 2 diabetes*. Pediatr. Diabetes 6, 129–135 (2005). - PubMed - DOI
• Desai, R. et al. Temporal trends in the prevalence of diabetes decompensation (diabetic ketoacidosis and hyperosmolar hyperglycemic state) among adult patients hospitalized with diabetes mellitus: A nationwide analysis stratified by age, gender, and race. Cureus 11, e4353 (2019). - PubMed - PMC
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• Published: 20 July 2024

Risk of chronic kidney disease in patients with a hyperglycemic crisis as the initial presentation of type 2 diabetes

• Chun-Ta Huang 1 , 2 ,
• Chih-Hsin Muo 3 ,
• Fung-Chang Sung   ORCID: orcid.org/0000-0003-3542-8552 3 , 4 , 5 &
• Pei-Chun Chen 6  

Scientific Reports volume  14 , Article number:  16746 ( 2024 ) Cite this article

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Metrics details

• Chronic kidney disease
• Outcomes research
• Type 2 diabetes

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan’s insurance claims from adults newly diagnosed with type 2 diabetes during 2006–2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018’s end, calculating the hazard ratio (HR) with the Cox model . Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91–2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59–1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33–2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29–2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

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Introduction.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) represent life-threatening hyperglycemic crises (HC) in patients with diabetes 1 . Although commonly seen in patients with preexisting diabetes, up to 20% of cases occur in those newly diagnosed 2 , 3 , 4 . Individuals with HC episodes face higher risks of subsequent morbidity and mortality compared with those without such episodes 5 , 6 , 7 . However, limited research explores the risk of chronic complications in patients experiencing HC during diabetes diagnosis, underscoring the need for further investigation.

Previous studies have reported an increased risk of subsequent stroke 8 , 9 , cardiovascular events 10 , long-term mortality 11 , 12 , and end-stage renal disease 13 in patients with diabetes who have experienced an HC. Nevertheless, these studies overlook the confounding effect of glycemic control on the development of diabetes-related chronic complications. Moreover, type 1 and type 2 diabetes possess distinct pathophysiologies and should not be considered as a single entity; however, only two studies exclusively included patients with type 2 diabetes 8 , 9 , and none were conducted in patients with newly diagnosed diabetes. In contrast, an Italian multicenter cohort study demonstrated that patients with DKA upon type 1 diabetes onset were not at an increased risk of diabetic retinopathy or albuminuria 14 . The reasons behind these conflicting findings and the impact of HC that occurs in patients newly diagnosed with type 2 diabetes remain to be elucidated.

Therefore, in this study, we aimed to examine the risk of developing chronic kidney disease (CKD), one of the major chronic complications of diabetes, in patients experiencing HC upon type 2 diabetes diagnosis. We hypothesized that HC occurring upon type 2 diabetes diagnosis is associated with a higher risk of developing CKD. Our findings could hold significance if this unique initial presentation of type 2 diabetes can be utilized to identify patients at increased risk of developing CKD; moreover, it could facilitate the implementation of preventive interventions to reduce CKD risk in this population.

Data sources

In this study, we utilized Taiwan’s insurance claims data to identify adults newly diagnosed with type 2 diabetes between 2006 and 2015. We used the Taiwan National Health Insurance Research Database (NHIRD), a comprehensive repository established in 1995 that covers over 99% of the nation’s residents 15 , 16 . The NHIRD comprises encrypted records encompassing sociodemographic information, household income, residency, outpatient/inpatient care, and prescribed medications. Diseases in the NHIRD are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) before 2016 and Tenth Revision (ICD-10-CM). Previous investigations have validated the NHIRD’s accuracy and reliability for population-based studies 17 , 18 .

Design setting and study cohorts

From the NHIRD, we used the ICD-9-CM or ICD-10-CM and Anatomical Therapeutic Chemical Codes (Tables S1 and Table S2 ) to identify newly diagnosed cases with type 2 diabetes (ICD-9-CM codes: 250. X0 or 250. × 2) during the study period (Fig.  1 ). We excluded individuals who were diagnosed with diabetes or using glucose-lowering drugs before the study period, younger than 20 years of age, had a history of kidney disease including benign or malignant neoplasms of the kidney, chronic kidney disease of any cause, glomerulonephritis, nephrotic syndrome, urolithiasis, and congenital renal anomalies, or were deceased at baseline. Individuals with concurrent HC at the time of their type 2 diabetes diagnosis (first-time type 2 diabetes diagnosis appeared with at least one of the following ICD-9-CM codes: 250.10, 250.12, 250.20, or 250.22) were categorized into the HC cohort. The clinical diagnostic criteria for HC were based on previous guidelines 19 , 20 , and our data were based on diagnostic codes from all medical facilities regardless of inpatient/outpatient care or emergency department visits. Regarding individuals without HC, we selected a control (non-HC) cohort with the same sample size frequency matched by diagnosis year and propensity score. The propensity scores were calculated using multivariable logistic regression for each person at baseline, including sex, age, type of residence, enrollment category, monthly income, comorbidities, and use of angiotensin-converting enzyme inhibitors ( ACEis) or angiotensin II receptor blockers (ARBs) . Comorbidities were diseases with at least two outpatient claims or one inpatient claim within 1 year of the index date and included hypertension, heart failure, coronary artery disease, ischemic stroke, transient ischemic attack, peripheral arterial disease, hyperlipidemia, obesity, and malignancy. Variables with a between-group standardized mean difference of < 0.1 were considered well-balanced 21 . Sodium-glucose cotransporter-2 inhibitors were not included due to their unavailability in Taiwan during the enrollment period.

Flow chart showing the establishment of the hyperglycemic crisis cohort and propensity score matched non-hyperglycemic crisis cohort from the National Health Insurance Research Database, Taiwan, 2006–2018. OAD, oral anti-diabetic agent.

The two cohorts were followed up until the end of 2018. Our outcome of interest was the combined incidence of CKD (ICD-9-CM codes: 585–586; ICD-10-CM code: N184–N186, N189–N19) or diabetic kidney disease (DKD) (ICD-9-CM codes: 250.40 or 250.42; ICD-10-CM: E112), or both. In Taiwan, it is generally accepted that CKD is characterized by a decreased glomerular filtration rate of less than 60 mL/min per 1.73 m 2 and/or markers of kidney damage that persist for longer than 3 months. DKD is a clinical diagnosis that refers to those cases with CKD presumed to be caused by diabetes. Clinicians are free to use whichever code is appropriate based on their judgment. Hence, the data of patients with diabetes and CKD may be coded using CKD, DKD, or both. As DKD is within the spectrum of CKD and our aim was to explore the risk of CKD, we used both codes to maximize the probability of capturing our main outcome of interest.

Institutional review board statement

This study was approved by the Institutional Review Board of Mackay Memorial Hospital (approval number: 22MMHIS382e). Our study was performed in accordance with the Declaration of Helsinki and all our methods were carried out under relevant guidelines and regulations. As all personal identifications in the database were encrypted and unidentifiable, the requirement for informed consent from the insured individuals was waived.

Statistical analysis

Baseline characteristics and comorbidities were compared between the HC and non-HC cohorts using Pearson’s χ 2 test for categorical variables and Student’s t -test for continuous variables. The HC cohort comprised three sub-cohorts: patients with DKA (ICD-9-CM codes: 250.10 or 250.12), HHS (ICD-9-CM codes: 250.20 or 250.22), and combined DKA and HHS (DKA-HHS). The cumulative incidence rate of combined CKD and DKD between the HC and non-HC cohorts, as well as between the HC sub-cohorts, was estimated and plotted using the Kaplan–Meier method. Inter-group differences were examined using the log-rank test. Cox proportional hazards regression analysis was used to calculate the crude hazard ratio comparing the HC and non-HC cohorts; moreover, the adjusted hazard ratio (aHR), along with its corresponding 95% confidence interval (CI), was used for the combined occurrence of CKD and DKD. The aHR was estimated after adjusting for age, sex, socioeconomic factors, and significant comorbidities. As patients who died before the event occurred will never be coded with CKD and/or DKD, the competing risk of death was managed using the Fine-Grey analysis model to estimate the sub-distribution hazard ratio (sHR) 22 . To address potential misclassification and pollution bias from claims data, where type 1 diabetes might have been incorrectly recorded as type 2 diabetes, we performed a subgroup analysis to estimate the combined incidence rates of CKD and DKD for individuals aged 40 years and older. We selected this cutoff because the incidence of type 1 diabetes drops significantly after age 40 years and remains relatively low in this age group. This approach helps to minimize the risk of pollution bias in our results 23 . To validate that the incident events were not the result of undiagnosed preexisting CKD or DKD, a supplementary sensitivity analysis was performed by excluding outcomes that occurred within 6 months after the diagnosis of type 2 diabetes. Finally, we conducted a nested case–control analysis to explore the risk factors for CKD or DKD, including DKA, HHS, acute kidney injury, nonsteroidal anti-inflammatory drug use, and ACEi or ARB use. Medication use was stratified based on the prescription length into three categories: no exposure (0 days), 90 days or less, and more than 90 days. Statistical analyses were performed using the Statistical Package for SAS V. 9.4 (SAS Institute, Cary, North Carolina, USA), and a two-sided P -value of less than 0.05 was considered statistically significant.

Ethics-approval and consent to participate

This study was approved by the Institutional Review Board of Mackay Memorial Hospital (approval number: 22MMHIS382e) and informed consent was waived.

Presentation at a meeting

The current study was presented as an e-poster at the IDF 2022 Congress in Lisbon, Portugal, on December 5–8.

Cohort characteristics

There were 13,242 participants in each cohort (Fig.  1 ), and their baseline characteristics are shown in Table 1 . The mean age of the study participants was approximately 54 years (men: 62%). Compared with the non-HC cohort, the HC cohort had a lower income and higher prevalence of malignancy (6.24% vs. 2.99%, respectively); however, they had a lower prevalence of hypertension (32.7% vs. 37.5%, respectively) and hyperlipidemia (13.2% vs. 20.7%, respectively). The two cohorts did not differ in the proportion of patients who received either ACEis or ARBs.

Combined incidence of CKD and DKD

Table 2 depicts the combined incidence of CKD and DKD in the HC cohort, its sub-cohorts, and in the non-HC cohort. The HC cohort comprised mainly patients with DKA (55.1%) and HHS (39.2%), with a few cases of combined DKA-HHS (5.7%). There were 4106 (31%) and 2735 (20.7%) events observed in the HC and non-HC cohorts during median follow-ups of 4.97 years and 7.15 years, respectively. This corresponded to incidence rates of 56.47 and 28.49 per 1000 person-years, respectively. The cumulative incidence of CKD and DKD was significantly greater in the HC cohort than in the non-HC cohort (Fig.  2 A). Within the HC cohort, the cumulative incidence was higher in patients with HHS and combined DKA-HHS than in those with DKA (Fig.  2 B). The aHR among the HC sub-cohorts increased from 1.69 (95% CI 1.59–1.79) for DKA to 2.47 (95% CI 2.33–2.63) for HHS and 2.60 (95% CI 2.29–2.95) for combined DKA-HHS. In the sub-distribution hazard models, the sHRs were attenuated but remained significantly higher in the main HC cohort and its sub-cohorts.

Group comparisons of the Kaplan–Meier estimated cumulative incidence of combined chronic kidney disease and diabetic kidney disease between hyperglycemic crisis (HC) and non-hyperglycemic crisis (non-HC) cohorts ( A ), and among hyperglycemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), combined DKA-HHS sub-cohorts and non-HC cohorts ( B ), from the National Health Insurance Research Database, Taiwan, 2006–2018.

Subgroup analysis in individuals aged 40 years and older

There were 10,266 (77.5%) and 10,419 (78.7%) individuals aged 40 years and older in the HC and non-HC cohorts, respectively (Table 3 ). This subgroup comprised 5104 (49.7%) individuals with DKA and 4591 (44.7%) with HHS in the HC cohort. A similar increase in the HR between the HC and non-HC cohorts, compatible with the result in our primary analysis, was observed in this age group. The aHR among the HC sub-cohorts also showed a stepwise escalation from 1.62 (95% CI 1.51–1.72) for DKA to 2.33 (95% CI 2.19–2.49) for HHS and 2.59 (95% CI 2.25–2.98) for combined DKA-HHS.

Sensitivity analysis

The sensitivity analysis demonstrated that the patterns of CKD or DKD development 6 months after the diagnosis of type 2 diabetes were consistent with the findings of the primary analysis (Table S3 ).

Nested case–control analyses

The nested case–control analysis showed that the risk of developing CKD or DKD was significantly higher for patients with a history of hyperlipidemia (adjusted odds ratio [aOR] 1.22; 95% CI 1.15–1.30), acute kidney injury (aOR 1.33; 95% CI 1.18–1.50), DKA (aOR 1.56; 95% CI 1.47–1.66), and HHS (aOR 1.75; 95% CI 1.64–1.86). Compared with patients who did not receive ACEis or ARBs, those who had received treatment with ACEis or ARBs also had a higher risk, with an aOR of 1.93 (95% CI 1.75–2.13) for those treated for 90 days or less and an aOR of 1.69 (95% CI 1.57–1.82) for those who were treated for more than 90 days (Table S4 ).

This population-based cohort study revealed a higher risk of incident CKD and/or DKD in patients with HC as their initial presentation of type 2 diabetes than in patients who present type 2 diabetes without HC. This association remained consistent across all HC sub-cohorts and stayed significant in the subgroup analysis for those aged 40 years and older. The risk was higher in patients with HHS and in those with both DKA and HHS than in those with DKA. This association remained robust after excluding cases that appeared within 6 months of diabetes diagnosis. Our nested case–control analysis corroborates that, compared with patients with type 2 diabetes who did not develop CKD or DKD, those who did were more likely to have experienced HC upon diabetes diagnosis.

The surprisingly high proportion of patients having DKA instead of HHS on the initial presentation of their type 2 diabetes in our cohort may raise concerns of pollution bias by the presence of patients with type 1 diabetes. Although there is currently no data reporting the proportion of DKA versus HHS in patients with HC as the initial presentation of type 2 diabetes, we believe that our findings are valid because previous studies have also reported a high percentage of newly diagnosed type 2 diabetes among patients with DKA. In an early study of 141 episodes of DKA in a tertiary referral center in Taiwan, 32 (22.7%) episodes were caused by newly diagnosed diabetes 24 . Twenty-five of the newly diagnosed patients were followed for at least 12 months, and 11 (44%) of them were not using insulin and exhibited metabolic features of type 2 diabetes. A recent study that retrospectively reviewed the medical records of consecutive patients with index DKA in four general hospitals in Qatar showed that 442 (48%) of them had type 2 diabetes 25 . Of the 324 patients with DKA and newly diagnosed diabetes, 176 (54.3%) had type 2 diabetes, and 93 (52.8%) were Asian. We speculate that the excessive DKA cases observed in our study and previous studies may be attributed to ‘ketosis-prone diabetes (KPD)’ 26 . This syndrome is characterized by the acute onset of severe hyperglycemia with ketoacidosis, necessitating hospital admission and treatment. However, it often undergoes spontaneous remission, with patients maintaining long-term insulin independence several weeks after discharge 27 . Initially identified in individuals of African descent and African Americans 28 , KPD is now recognized as a significant clinical entity in Asian populations 27 . Patients with KPD are typically young or middle-aged and predominantly male 29 , consistent with the clinical characteristics of our study population. Another reason we believe that we secured the cases of type 2 diabetes in our study is due to the unique characteristics of the NHIRD. In Taiwan, type 1 diabetes is classified as a catastrophic illness by the National Health Insurance Administration. When a physician diagnoses a patient with such a condition, the patient can apply for a catastrophic illness certificate by submitting the necessary documentation. Upon issuance, this certification is recorded on the patient’s National Health Insurance Card. During the validity period of this certificate, patients are exempt from co-payment of outpatient or inpatient care related to the certified illness 30 . However, this exemption is contingent upon the physician using the correct ICD codes, as is the case with type 1 diabetes. An incorrect ICD coding that misclassifies type 1 diabetes as type 2 diabetes would prevent patients with type 1 diabetes from receiving exemptions for medical expenses, a scenario which is unlikely to occur in real-world practice or in the NHIRD. Moreover, the result of our subgroup analysis for those aged 40 years and older, which comprised nearly 78% of all patients, did not differ from our main findings. As the incidence of type 2 diabetes increases with age in Taiwan, and the incidence of type 1 diabetes over 40 years of age is remarkably low (0.02 per 100,000 population) 23 , the possibility that our findings are biased due to the presence of patients with type 1 diabetes is negligibly low.

Our findings align with those of previous Taiwan NHIRD studies demonstrating the detrimental effects of HC in patients with diabetes 8 , 9 , 10 , 11 , 12 , 13 . The present research adds value to the previous literature in several aspects. First, unlike previous studies that examined diabetes as a single entity 10 , 11 , 12 , 13 , we focused exclusively on type 2 diabetes and examined the individual effects of different types of HC. Given the distinct pathophysiologies underlying DKA and HHS, as well as those underlying type 1 and type 2 diabetes, our study design may ensure a more robust association between HC and CKD. The higher risk of CKD and/or DKD observed in patients with HHS or those with combined DKA-HHS than in patients with isolated DKA also aligns with previous studies reporting worse in-hospital outcomes in patients with combined DKA-HHS than in those with isolated DKA or HHS 31 . Second, HC typically signifies uncontrolled diabetes 32 , which is a well-recognized risk factor for diabetic complications 33 . Studies not adjusting for patients’ glycemic control may confound the impact of HC on long-term outcomes. We minimized such confounding by focusing on patients newly diagnosed with diabetes, where subsequent glycemic control acts as a mediator or effect modifier that requires no adjustment. Third, this pioneering study investigates the impact of HC on patients newly diagnosed with type 2 diabetes without prior kidney disease, offering potential insights for future clinical practice. Given their increased risk of CKD, patients experiencing HC upon type 2 diabetes diagnosis should receive proactive early preventive measures to mitigate such risk.

Several mechanisms may explain our findings. A longitudinal study on type 2 diabetes in Taiwan highlighted that individuals with lower income levels were more likely to have hospitalization-diagnosed diabetes, although it did not report how many of these patients were diagnosed via HC 34 . Patients with type 2 diabetes who are not diagnosed until hospitalization may be less likely to receive early detection screenings or may lack sufficient awareness of diabetes-related symptoms to seek appropriate healthcare 34 . Although the two study groups in our study did not differ in most baseline characteristics after propensity-score matching, individuals in the HC group exhibited significantly lower income levels than those in the non-HC group. Such difference may suggest that our HC group, compared with the non-HC group, included more individuals facing healthcare inequality, potentially resulting in worse renal outcomes. Furthermore, common risk factors for CKD, such as hypertension and hyperlipidemia, often remain undiagnosed among underprivileged individuals 35 . The paradoxically higher risk of CKD despite a lower prevalence of hypertension and hyperlipidemia in the HC group than in the non-HC group may be a result of more undiagnosed rather than healthier cases in the former group. As our propensity score considered only established comorbidities, the true risk difference of CKD at baseline between the two groups may be unbalanced. This could explain the remaining two-fold higher risk of CKD in the HC group, even after adjusting for income level, comorbidities, and other covariates.

From a biological perspective, our finding may be a consequence of initial priming by hyperglycemia, as the onset of diabetes followed by subsequent insults from acute kidney injury (AKI) during HC ultimately leads to persistent nephron damage. Hyperglycemia-induced epigenetic change can lead to progressive and irreversible renal injury, a phenomenon known as the “metabolic memory of DKD” 36 . Following exposure to hyperglycemia, vascular endothelial cells continue to increase oxidative stress and elicit inflammation even after normalization of blood glucose levels 37 . Owing to the slow progression of type 2 diabetes, the exact duration between disease onset and diagnosis is difficult to ascertain. Previous studies have suggested that the interval between the onset and diagnosis of type 2 diabetes is at least 5 years 38 , 39 . Moreover, low income is significantly associated with delayed diagnosis and inadequate diabetes care and management 34 . We speculate that patients experiencing HC upon diabetes diagnosis had a longer duration from diabetes onset to diagnosis compared with those who had diabetes diagnosed without HC. Such a latent period aggravates metabolic memory and leads to an increased risk of CKD. Moreover, AKI is a known risk factor for CKD 40 , 41 , 42 and is common in patients with DKA due to volume depletion 7 , 43 . Despite this, there is a paucity of data reporting the incidence of AKI during HHS. A higher rate of AKI in patients with HHS is expected as patients with HHS are more likely to be dehydrated than patients with DKA. The occurrence of AKI during HC may exacerbate renal damage and increase the risk of CKD. A recent study revealed a higher incidence of AKI in patients with HHS and combined DKA-HHS than in those with DKA 44 , which may also explain the greater risk of CKD in patients with HHS and combined DKA-HHS than in those with DKA in our study. Nevertheless, we cannot exclude the possibility that our findings result from surveillance bias between the two cohorts. As patients experiencing HC upon diabetes diagnosis have more severe disease compared with those without HC at diagnosis, clinicians should provide more vigilant follow-ups for earlier detection of CKD.

This study had some limitations. First, relying solely on claims data may have led to the misclassification of diseases. However, the accuracy and validity of the NHIRD claims data have been demonstrated previously 15 , 17 , 18 , minimizing the impact of misclassification on our results. Second, we could not adjust for covariates unavailable in the NHIRD, including laboratory tests, blood pressure, waist circumference, body mass index, and lifestyle. The potential impact of this missing data remains unassessed. Furthermore, the inherent limitations of the NHIRD also restricted us from determining the severity of DKA and the stage of CKD, which may also have affected our results. Third, in large-sample studies, even minor differences can achieve statistical significance, warranting cautious interpretation. Because we established our study cohorts using a propensity score-matched design and conducted the analysis using stratification, we believe that the observed risk differences between the two cohorts were not a result of overpowering. Finally, the generalizability of our findings may be limited to populations with similar characteristics.

Conclusions

Patients who experience HC upon type 2 diabetes diagnosis have a higher risk of developing CKD compared with those without HC at diagnosis. As type 2 diabetes and end-stage renal disease are highly prevalent in Taiwan, proactive preventive measures are imperative to mitigate risks in this vulnerable population. These interventions should include early introduction of ACEis or ARBs and sodium-glucose cotransporter-2 inhibitors, stringent control of diabetes and the reduction of other risk factors, and educational programs for continuous diabetes self-care management. Furthermore, healthcare authorities should reinforce government-subsidized diabetes screening programs, especially for the underprivileged, to facilitate early recognition of undiagnosed diabetes and prevent HC incidents.

Data availability

No original data were generated or collected as part of this study. The NHIRD used in this study is available from the Taiwan National Health Insurance Administration, Ministry of Health and Welfare.

Gosmanov, A. R. et al. Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State (Endotext, 2021).

Google Scholar  

Misra, S. et al. Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: A population-based study. Lancet Diabetes Endocrinol. 9 , 671–680 (2021).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Wachtel, T. J., Tetu-Mouradjian, L. M., Goldman, D. L., Ellis, S. E. & O’Sullivan, P. S. Hyperosmolarity and acidosis in diabetes mellitus: A three-year experience in Rhode Island. J. Gen. Intern. Med. 6 , 495–502 (1991).

Article   CAS   PubMed   Google Scholar  

Fourtner, S. H., Weinzimer, S. A. & Levitt Katz, L. E. Hyperglycemic hyperosmolar non-ketotic syndrome in children with type 2 diabetes*. Pediatr. Diabetes 6 , 129–135 (2005).

Article   PubMed   Google Scholar  

Desai, R. et al. Temporal trends in the prevalence of diabetes decompensation (diabetic ketoacidosis and hyperosmolar hyperglycemic state) among adult patients hospitalized with diabetes mellitus: A nationwide analysis stratified by age, gender, and race. Cureus 11 , e4353 (2019).

PubMed   PubMed Central   Google Scholar  

Lawrence, S. E., Cummings, E. A., Gaboury, I. & Daneman, D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J. Pediatr. 146 , 688–692 (2005).

Orban, J. C., Maizière, E. M., Ghaddab, A., Van Obberghen, E. & Ichai, C. Incidence and characteristics of acute kidney injury in severe diabetic ketoacidosis. PLOS One 9 , e110925 (2014).

Article   ADS   PubMed   PubMed Central   Google Scholar  

Wang, J. Y. et al. Increased risk of ischemic stroke after hyperosmolar hyperglycemic state: A population-based follow-up study. PLOS One 9 , e94155 (2014).

Chen, Y. L., Weng, S. F., Yang, C. Y., Wang, J. J. & Tien, K. J. Long-term risk of stroke in type 2 diabetes patients with diabetic ketoacidosis: A population-based, propensity score-matched, longitudinal follow-up study. Diabetes Metab. 43 , 223–228 (2017).

Chang, L. H. et al. Association between hyperglycaemic crisis and long-term major adverse cardiovascular events: a nationwide population-based, propensity score-matched, cohort study. BMJ Open. 6 , e012233 (2016).

Article   PubMed   PubMed Central   Google Scholar  

Kao, Y. et al. Subsequent mortality after hyperglycemic crisis episode in the non-elderly: A national population-based cohort study. Endocrine 51 , 72–82 (2016).

Huang, C. C. et al. Long-term mortality risk after hyperglycemic crisis episodes in geriatric patients with diabetes: A national population-based cohort study. Diabetes Care 38 , 746–751 (2015).

Kao, Y. et al. Association of hyperglycemic crisis with an increased risk of end-stage renal disease: A nationwide population-based cohort study. Diabetes Res. Clin. Pract. 138 , 106–112 (2018).

Salardi, S. et al. Ketoacidosis at diagnosis in childhood-onset diabetes and the risk of retinopathy 20years later. J. Diabetes Complicat. 30 , 55–60 (2016).

Article   Google Scholar  

Lin, L. Y., Warren-Gash, C., Smeeth, L. & Chen, P. C. Data resource profile: The National Health Insurance Research Database (NHIRD). Epidemiol. Health 40 , e2018062 (2018).

Wang, T. H., Tsai, Y. T. & Lee, P. C. Health big data in Taiwan: A national health insurance research database. J. Formos. Med. Assoc. 122 , 296–298 (2023).

Lin, C. C., Lai, M. S., Syu, C. Y., Chang, S. C. & Tseng, F. Y. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan. J. Formos. Med. Assoc. 104 , 157–163 (2005).

PubMed   Google Scholar  

Hsieh, M. T., Hsieh, C. Y., Tsai, T. T., Wang, Y. C. & Sung, S. F. Performance of ICD-10-CM diagnosis codes for identifying acute ischemic stroke in a national health insurance claims database. Clin. Epidemiol. 12 , 1007–1013 (2020).

Kitabchi, A. E., Umpierrez, G. E., Murphy, M. B. & Kreisberg, R. A. Hyperglycemic crises in adult patients with diabetes: A consensus statement from the American Diabetes Association. Diabetes Care 29 , 2739–2748 (2006).

Kitabchi, A. E., Umpierrez, G. E., Miles, J. M. & Fisher, J. N. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32 , 1335–1343 (2009).

Nguyen, T. L. et al. Double-adjustment in propensity score matching analysis: Choosing a threshold for considering residual imbalance. BMC Med. Res. Methodol. 17 , 78 (2017).

Fine, J. P. & Gray, R. J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94 , 496–509 (1999).

Article   MathSciNet   Google Scholar  

Sheen, Y. J. et al. Trends in prevalence and incidence of diabetes mellitus from 2005 to 2014 in Taiwan. J. Formos. Med. Assoc. 118 (suppl 2), S66–S73 (2019).

Yan, S. H., Sheu, W. H., Song, Y. M. & Tseng, L. N. The occurrence of diabetic ketoacidosis in adults. Intern. Med. 39 , 10–14 (2000).

Ata, F. et al. Differential evolution of diabetic ketoacidosis in adults with pre-existent versus newly diagnosed type 1 and type 2 diabetes mellitus. BMC Endocr. Disord. 23 , 193 (2023).

Gaba, R., Mehta, P. & Balasubramanyam, A. Evaluation and management of ketosis-prone diabetes. Expert. Rev. Endocrinol. Metab. 14 , 43–48 (2019).

Lebovitz, H. E. & Banerji, M. A. Ketosis-prone diabetes (flatbush diabetes): An emerging worldwide clinically important entity. Curr. Diabetes Rep. 18 , 120 (2018).

Banerji, M. A. et al. GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. Diabetes 43 , 741–745 (1994).

Wang, X. & Tan, H. Male predominance in ketosis-prone diabetes mellitus. Biomed. Rep. 3 , 439–442 (2015).

National Health Insurance Administration, Ministry of Health and Welfare, Taiwan: Policies and Services: Care for Special Groups (Accessed 15 June 2024). https://www.nhi.gov.tw/en/cp-90-d4e0a-18-2.html

Pasquel, F. J. et al. Clinical outcomes in patients with isolated or combined diabetic ketoacidosis and hyperosmolar hyperglycemic state: A retrospective, hospital-based cohort study. Diabetes Care 43 , 349–357 (2020).

Chou, W. et al. Clinical characteristics of hyperglycemic crises in patients without a history of diabetes. J. Diabetes Investig. 5 , 657–662 (2014).

An, J. et al. Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes. BMJ Open Diabetes Res. Care 9 , e001847 (2021).

Hsu, C. C. et al. Poverty increases type 2 diabetes incidence and inequality of care despite universal health coverage. Diabetes Care 35 , 2286–2292 (2012).

Ayanian, J. Z., Zaslavsky, A. M., Weissman, J. S., Schneider, E. C. & Ginsburg, J. A. Undiagnosed hypertension and hypercholesterolemia among uninsured and insured adults in the Third National Health and Nutrition Examination Survey. Am. J. Public Health 93 , 2051–2054 (2003).

Kato, M. & Natarajan, R. Epigenetics and epigenomics in diabetic kidney disease and metabolic memory. Nat. Rev. Nephrol. 15 , 327–345 (2019).

El-Osta, A. et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J. Exp. Med. 205 , 2409–2417 (2008).

Harris, M. I., Klein, R., Welborn, T. A. & Knuiman, M. W. Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis. Diabetes Care 15 , 815–819 (1992).

Porta, M. et al. Estimating the delay between onset and diagnosis of type 2 diabetes from the time course of retinopathy prevalence. Diabetes Care 37 , 1668–1674 (2014).

Thakar, C. V., Christianson, A., Himmelfarb, J. & Leonard, A. C. Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus. Clin. J. Am. Soc. Nephrol. 6 , 2567–2572 (2011).

Coca, S. G., Singanamala, S. & Parikh, C. R. Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int. 81 , 442–448 (2012).

Hsu, R. K. & Hsu, C. Y. The role of acute kidney injury in chronic kidney disease. Semin. Nephrol. 36 , 283–292 (2016).

Myers, S. R. et al. Frequency and risk factors of acute kidney injury during diabetic ketoacidosis in children and association with neurocognitive outcomes. JAMA Netw. Open 3 , e2025481 (2020).

Schmitt, J., Rahman, A. F. & Ashraf, A. Concurrent diabetic ketoacidosis with hyperosmolality and/or severe hyperglycemia in youth with type 2 diabetes. Endocrinol. Diabetes Metab. 3 , e00160 (2020).

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Acknowledgements

We are grateful to the Health Data Science Center of China Medical University Hospital for providing administrative, technical, and funding support.

This work was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (Grant Number: MOHW110-TDU-B-212-124004), the Ministry of Science and Technology (grant number: MOST 110-2321-B-039-003), and China Medical University Hospital (Grant Numbers: DMR-111-228 and CMU110-MF-63). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Chih-Hsin Muo & Fung-Chang Sung

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Conception and design: CT, FC. Acquisition, analysis, and interpretation of data: all authors. Drafting of the manuscript: CT. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: CH. Obtained funding: FC, PC. All authors had full access to all the study data and take responsibility for its integrity and the accuracy of data analysis. All authors have read and approved the final version of the manuscript submitted for publication.

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Huang, CT., Muo, CH., Sung, FC. et al. Risk of chronic kidney disease in patients with a hyperglycemic crisis as the initial presentation of type 2 diabetes. Sci Rep 14 , 16746 (2024). https://doi.org/10.1038/s41598-024-67678-3

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Journal of Diabetology

Short Communication - Journal of Diabetology (2024) Volume 8, Issue 3

Outlook and Potential Issues of Hyperosmolar Hyperglycemic State

Article type: Short Communication

Homepage URL: https://www.alliedacademies.org/journal-diabetology/

Journal short name: J Diabetol

PDF No: 203

Citation: Vink H. Exploring Diabetes Mellitus: Comprehensive Insights into Its Causes, Symptoms, and Treatments. J Diabetol. 2024;8(3):203

*Correspondence to: Hans Vink, Department of Physiology, Universiteitssingel, Maastricht, The Netherlands. E-mail: [email protected]

Received: 27-Apr-2024, Manuscript No. AADY-25-139528; Editor assigned: 29-Apr-2024, PreQC No. AADY-24-139528 (PQ) ; Reviewed: 12-May-2024, QC No. AADY-24-139528 ; Revised: 17-May-2024, Manuscript No. AADY-24-139528 (R) ; Published: 23-May-2024, DOI:10.35841/aady-8.3.203

Introduction

Hyperosmolar Hyperglycemic State, formerly known as Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS), is a severe and life-threatening complication of diabetes mellitus. While it is less frequent than diabetic ketoacidosis (DKA), HYPEROSMOLAR HYPERGLYCEMIC STATE  is associated with significant morbidity and mortality, primarily affecting individuals with type 2 diabetes. This article aims to provide an in-depth exploration of hyperosmolar hyperglycemic state , its epidemiology, pathophysiology, clinical presentation, diagnosis, and management. Hyperosmolar Hyperglycemic State (HYPEROSMOLAR HYPERGLYCEMIC STATE ) is a life-threatening medical emergency characterized by extreme hyperglycemia, dehydration, and high osmolarity. Although less common than diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state  poses significant risks to individuals with diabetes, especially those with type 2 diabetes. This research article provides a comprehensive review of HYPEROSMOLAR HYPERGLYCEMIC STATE , including its epidemiology, pathophysiology, clinical presentation, diagnosis, and management. A better understanding of hyperosmolar hyperglycaemic state  is crucial for healthcare professionals to improve patient outcomes.

This comprehensive review of hyperosmolar hyperglycaemic state provides insights into its clinical relevance, pathophysiological basis, and the strategies required to manage and mitigate its impact on individuals with diabetes. With ongoing research and advancements in diabetes management, early recognition and prompt intervention can reduce the morbidity and mortality associated with this serious medical condition.

Epidemiology

Hyperosmolar hyperglycemic state is more common in older individuals with type 2 diabetes, but it can also affect those with type 1 diabetes or previously undiagnosed diabetes. The exact prevalence of hyperosmolar hyperglycemic state  is challenging to determine due to variations in diagnostic criteria and underreporting. However, it is clear that HYPEROSMOLAR HYPERGLYCEMIC STATE  remains a critical concern in diabetes management, often precipitated by factors such as infection, inadequate glycemic control, medication non-compliance, and concomitant illnesses.

Pathophysiology

The pathophysiology of hyperosmolar hyperglycemic state involves a profound state of hyperglycemia, hyperosmolarity, and dehydration. It is characterized by insulin deficiency, typically not as severe as in DKA, and increased counterregulatory hormones. Hyperglycemia results in osmotic diuresis, causing excessive water loss and electrolyte imbalances. The hyperosmolarity in HYPEROSMOLAR HYPERGLYCEMIC STATE  can lead to severe neurological manifestations, making it distinct from DKA.

Clinical Presentation

The clinical presentation of hyperosmolar hyperglycemic state  is often insidious and can include the following features:

• Profound hyperglycemia, typically exceeding 600 mg/dL (33.3 mmol/L).
• Severe dehydration with signs of hypovolemic shock, such as tachycardia, hypotension, and decreased skin turgor.
• Altered mental status, ranging from confusion to coma, which is a hallmark of hyperosmolar hyperglycemic state .
• Neurological symptoms, including seizures, focal deficits, and hemiparesis, due to hyperosmolarity.
• Laboratory findings may reveal an increased serum osmolarity, high blood glucose levels, and minimal to no ketonemia or ketonuria.

The diagnosis of hyperosmolar hyperglycemic state is primarily clinical, with laboratory confirmation. Essential diagnostic criteria include:

• Severe hyperglycemia (often >600 mg/dL or 33.3 mmol/L).
• Profound dehydration and clinical signs of hypovolemia.
• Altered mental status, ranging from confusion to coma.
• Increased serum osmolarity (>320 mOsm/kg).
• Laboratory investigations should also include electrolyte assessment, arterial blood gas analysis, and exclusion of other possible causes of hyperglycemia and altered consciousness, such as stroke or sepsis.

The management of hyperosmolar hyperglycemic state  is multifaceted and aims to correct hyperglycemia, dehydration, and electrolyte imbalances while addressing underlying precipitating factors. Key components of hyperosmolar hyperglycemic state  management include:

• Aggressive rehydration with isotonic saline to restore vascular volume.
• Correction of electrolyte imbalances, including potassium and phosphate replacement.
• Gradual reduction of hyperglycemia with intravenous insulin therapy.
• Identification and treatment of precipitating factors, such as infections.
• Frequent monitoring of blood glucose, electrolytes, and clinical status.

Close supervision in an intensive care setting, especially in severe cases.

Prognosis and Complications

The prognosis of hyperosmolar hyperglycemic state depends on the timely diagnosis and appropriate management of the condition. Mortality rates are highest in older adults with comorbidities, but with adequate medical attention, most patients can recover. Nevertheless, hyperosmolar hyperglycemic state can lead to complications such as organ failure, thrombosis, and neurological deficits, underscoring the importance of vigilant management.

Hyperosmolar Hyperglycemic State is a severe and life-threatening complication of diabetes that predominantly affects individuals with type 2 diabetes. Understanding its epidemiology, pathophysiology, clinical presentation, diagnosis, and management is essential for healthcare professionals to improve patient outcomes. The prevention of hyperosmolar hyperglycemic state through optimal diabetes care, including glycemic control and patient education, remains a critical goal in reducing its incidence.

• Ramesh A, Chhabra P, Brayman KL. Pancreatic islet transplantation in type 1 diabetes mellitus: an update on recent developments . Curr. Diabetes Rev. 2013;9(4):294-311.

Indexed at, Google Scholar , Cross Ref

• Shapiro AJ, Pokrywczynska M, Ricordi C. Clinical pancreatic islet transplantation . Nature Reviews Endocrinology. 2017;13(5):268-77.
• Arutyunyan IV, Fatkhudinov TK, Makarov AV, et al. Regenerative medicine of pancreatic islets . World J Gastroenterol. 2020;26(22):2948.
• Triolo TM, Bellin MD. Lessons from human islet transplantation inform stem cell-based approaches in the treatment of diabetes . Front Endocrinol. 2021;12:636824.
• Bottino R, Knoll MF, Knoll CA, et al. The future of islet transplantation is now . Front Med. 2018;5:202.
• Maffi P, Secchi A. Islet transplantation alone versus solitary pancreas transplantation: an outcome-driven choice? . Curr Diab Rep. 2019;19:1-7.
• Sutherland DE, Gruessner A, Hering BJ. β-Cell replacement therapy (pancreas and islet transplantation) for treatment of diabetes mellitus: an integrated approach . Endocrinol Metab. 2004;33(1):135-48.
• Chhabra P, Sutherland DE, Brayman KL. Overcoming barriers in clinical islet transplantation: current limitations and future prospects . Curr Probl Surg. 2014;51(2):49-86.
• Merani S, Shapiro AJ. Current status of pancreatic islet transplantation . Clin Sci. 2006;110(6):611-25.
• Dholakia S, Mittal S, Quiroga I, et al. Pancreas transplantation: past, present, future . Am J Med. 2016;129(7):667-73.

• DOI: 10.54307/2024.nwmj.136
• Corpus ID: 271173298

An evaluation of clinical and epidemiological characteristics and autoantibody status of children with type 1 diabetes mellitus at presentation

• S. Bolu , A. Asik , I. Bucak
• Published in Northwestern Medical Journal 12 July 2024

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Increase in prevalence of diabetic ketoacidosis at diagnosis among youth with type 1 diabetes: the search for diabetes in youth study.

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Diabetic Ketoacidosis at Manifestation of Type 1 Diabetes in Childhood and Adolescence-Incidence and Risk Factors.

Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents, the incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in sweden: a 40 year follow-up, seasonal variation and epidemiological parameters in children from greece with type 1 diabetes mellitus (t1dm), ispad clinical practice consensus guidelines 2018: other complications and associated conditions in children and adolescents with type 1 diabetes, characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy, elevated anti‐tissue transglutaminase antibodies in children newly diagnosed with type 1 diabetes do not always indicate coeliac disease, incidence of type 1 diabetes in children aged below 18 years during 2013-2015 in northwest turkey, t cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes, related papers.

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Persistent Hypoglycemia in Diabetes Type 1 Patient with Medtronic 780 G Insulin Pump: A Case Report

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Maïté Verkest , Karl Logghe , Marlies Van Loocke; Persistent Hypoglycemia in Diabetes Type 1 Patient with Medtronic 780 G Insulin Pump: A Case Report. Horm Res Paediatr 2024; https://doi.org/10.1159/000539486

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Introduction: In this article, the importance of holistic care is highlighted trough the case of a 10-year-old female with diabetes type 1 presenting with recurrent severe hypoglycemia. Case Presentation: A 10-year-old female, with type 1 diabetes mellitus for 2 years, was hospitalized because of persistent hypoglycemia. At time of presentation, the patient was getting her insulin through an automated insulin delivery device. She came to the emergency room because of severe hypoglycemia despite adequate administration of glucagon intranasal and oral sugar solutions. The patient was hospitalized to resolve the hypoglycemia and to investigate the cause of the persistent hypoglycemia. Extensive further investigation was performed without result. Conclusion: After several conversations with psychologists, the patient admitted having manipulated the insulin pump resulting in auto-induced persistent and recurrent life-threatening hypoglycemia. Through camera monitoring, the team was able to confirm the manipulation.

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