Diabetes Mellitus

What is T2DM?

Type 2 diabetes mellitus (T2DM) is a chronic, progressive, and incompletely understood metabolic disease defined by the presence of chronic hyperglycemia. It is the leading cause of blindness, nontraumatic lower-limb amputation, and chronic kidney disease and a major cause of cardiovascular disease, leading to early death. The increasing incidence of T2DM is largely attributable to changes in lifestyle (diet and activity levels) and obesity. The problem is global, affects affluent and lower-income societies, has substantial adverse effects on health status and life span, and carries high societal costs. Commonly associated metabolic abnormalities include hypertension, dyslipidemia, inflammation, hypercoagulation, and endothelial-cell dysfunction.

Although resistance to some actions of insulin and inadequate secretion of insulin for the given metabolic state are the critical abnormalities in T2DM, several other factors contribute to the hyperglycemic state

Insulin resistance is typically present for some years before diagnosis, manifested as diminished stimulation of glucose transport in muscle and adipose tissue and inadequate suppression of glucose production in the liver in response to insulin. However, euglycemia is maintained as long as beta cells secrete higher amounts of insulin. Over time, insulin levels decline because of the decreased number of beta cells and their diminished secretory capacity. Longitudinal studies involving Pima Indians and other populations have shown a 50% or greater decrease in maximal beta-cell function at diagnosis. Abnormal postprandial suppression of glucagon secretion also occurs. Beta-cell failure is mediated by genetic factors and exposure to chronically elevated levels of blood glucose (glucotoxicity) and free fatty acids (lipotoxicity). Older age, amyloid fibrils in islets, and chronically high rates of insulin secretion also play mechanistic roles. The majority of genetic abnormalities that have been identified in patients with type 2 diabetes are related to beta-cell function.

According to the American Diabetes Association, the diagnosis of type 2 diabetes is based on a glycated hemoglobin level of 6.5% or more, a fasting plasma glucose level of 7.0 mmol per liter or more, or a 2-hour plasma glucose level of 11.1 mmol per liter or more during an oral glucose-tolerance test.6 The diagnosis can also be established by classic symptoms of hyperglycemia and a random plasma glucose level of 7.0 mmol per liter or more. Test results require confirmation with the use of the above criteria, unless the diagnosis is obvious on the basis of the symptoms. 

Glycemic Management of Type 2 Diabetes Mellitus. Faramarz Ismail-Beigi, M.D., Ph.D. 

N Engl J Med 2012; 366:1319-1327April 5, 2012

Executive Summary: Standards of Medical Care in Diabetes—2012

Current criteria for the diagnosis of diabetes

A1C ≥6.5%. The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program (NGSP)-certified and standardized to the Diabetes Control and Complications Trial (DCCT) assay;

or

fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h;

or

2-h plasma glucose ≥200 mg/dL (11.1 mmol/l) during an oral glucose tolerance test (OGTT). The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water;

or

in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/l); in the absence of unequivocal hyperglycemia, the result should be confirmed by repeat testing.

Testing for diabetes in asymptomatic patients

Testing to detect type 2 diabetes and to assess risk for future diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI ≥25 kg/m2) and who have one or more additional risk factors for diabetes. In those without these risk factors, testing should begin at age 45 years. (B)

If tests are normal, repeat testing at least at 3-year intervals is reasonable. (E)

To test for diabetes or to assess risk of future diabetes, A1C, FPG, or 2-h 75-g OGTT are appropriate. (B)

In those identified with increased risk for future diabetes, identify and, if appropriate, treat other cardiovascular disease (CVD) risk factors. (B)

Detection and diagnosis of gestational diabetes mellitus (GDM)

Screen for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, using standard diagnostic criteria. (B)

In pregnant women not previously known to have diabetes, screen for GDM at 24-28 weeks gestation, using a 75-g 2-h OGTT and the diagnostic cutpoints in Table 6 of the “Standards of Medical Care in Diabetes—2012”. (B)

Screen women with GDM for persistent diabetes at 6–12 weeks postpartum, using a test other than A1C. (E)

Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. (B)

Women with a history of GDM found to have prediabetes should receive lifestyle interventions or metformin to prevent diabetes. (A)

doi: 10.2337/dc12-s004Diabetes Care January 2012 vol. 35 no. Supplement 1