Progression from IGT to type 2 diabetes mellitus: the central role of impaired early insulin secretion

Impaired glucose tolerance (IGT) is characterized by plasma glucose responses to an oral glucose challenge that are above normal but not at the level defining diabetes. IGT is a common condition that greatly increases risk for the subsequent development of type 2 diabetes. Individuals with IGT manifest abnormalities in both insulin action and early insulin secretion similar to those seen in patients with type 2 diabetes. These abnormalities not only precede diabetes, they predict it as well. Furthermore, the progression from IGT to diabetes is characterized by a dramatic decline in early insulin secretion. It is now evident that early insulin secretion plays an important role in the rapid and efficient suppression of endogenous glucose production following a meal. Loss of early insulin secretion initially leads to post-prandial hyperglycemia which, as the disease progresses, worsens to clinical hyperglycemia. Obesity and a high fat diet may contribute to the development of both insulin resistance and insulin secretory dysfunction in susceptible individuals. Strategies that improve insulin resistance and enhance early insulin secretion may prevent the progression from IGT to diabetes. Already, there is substantial evidence the weight loss and exercise may reduce the risk of developing diabetes by up to 58%. Other trials using pharmacologic agents to decrease insulin resistance and increase early insulin secretion are underway. Prevention remains the best hope for a long-term solution to the worldwide epidemic of diabetes.