There is little doubt that we are in the midst of a worldwide epidemic of diabetes. There are an estimated 143 million people worldwide with the disease, almost five times more than estimates of ten years ago. This number will probably double by 2030 (Harris et al., 1998). Although diabetes is more prevalent in developed countries, it is likely that the developing world will bear the brunt of the epidemic in the future. In the US, almost 16 million people are thought to be afflicted, a third of whom are undiagnosed. The disease is considerably more common among the elderly and strikes African-, Mexican-and Native Americans at 1.7–3 times the rate for that of non-Hispanic whites. In patients with diabetes, the risk of heart disease and stroke are elevated 2–4 times. Moreover, diabetes is the leading cause of end stage renal disease, blindness, and nontraumatic limb amputation. While the human and economic costs of diabetes are difficult to calculate, the total medical costs incurred annually in the US alone are close to $100 billion.

Diabetes is defined as a state in which carbohydrate and lipid metabolism are improperly regulated by insulin. This results in elevated fasting and postprandial serum glucose that leads to complications if left untreated. There are two major categories of the disease, Types 1 and 2. Patients with Type 1 diabetes are absolutely dependent on exogenous insulin. This form of the disease may account for 5%–10% of all cases and is thought to result from the autoimmune destruction of the insulin-producing β cells of the islets of Langerhans. Type 2 diabetes is far more common and results from a combination of defects in insulin secretion and action. While the complications that arise from these two forms of the disease are similar, the diseases are completely different entities in terms of pathophysiology. Because of these major differences, I will restrict the scope of this review to the exciting new insights into the underlying pathophysiology and genetics of Type 2 diabetes, as well as new prospects for therapeutic intervention.