Early identification and treatment of insulin resistance: impact on subsequent prediabetes and type 2 diabetes.

Insulin resistance (IR) is characterized by decreasing sensitivity of target tissues to the action of insulin, elevated blood glucose concentration, and increased hepatic production of atherogenic lipids. IR is associated with declining insulin production by the pancreas, the emergence of type 2 diabetes, and increasing risk of cardiovascular disease (CVD). Clinical markers of IR include elevated plasma glucose concentration under fasting conditions or following ingestion of an oral glucose challenge. IR and hyperinsulinemia produce a number of effects that promote CVD, including adverse effects on blood pressure, endothelial cell function, lipid profile, platelet function, and blood coagulation. Glucose dysregulation often occurs in combination with other cardiovascular risk factors, including hypertension, obesity, and dyslipidemia. Clinical trials have shown that lifestyle changes to promote weight loss and medical therapy with insulin-sensitizing agents can reduce the likelihood of progression from early stages of IR to type 2 diabetes. However, it is important to recognize that obesity is a chronic condition that needs strategies beyond a diet plan to maintain sufficient weight loss over time. Pharmacologic therapies that are currently in development may help not only to promote weight loss but also to improve the symptoms of cardiometabolic risk in patients with and without diabetes.