Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia that results from tissue resistance to the glucoselowering effects of insulin and inadequate pancreatic B-cell compensation for that resistance (1). Longitudinal studies of people at risk for T2DM reveal that insulin resistance is often present years before the onset of hyperglycemia (2–4). Studies of the evolution of diabetes during a relatively short period (ie 5–7 yr) before the diagnosis in Mexican Americans and Pima Indians have revealed that: 1) poor B-cell function and insulin resistance precede and predict the development of diabetes (4, 6); and 2) the progression from normal glucose tolerance to diabetes is attended by a decline in B-cell function and an increase in insulin resistance (6). These findings indicate that insulin resistance and B-cell dysfunction both occur in people who develop T2DM. They do not reveal whether declining B-cell function is an independent event that is simply coincident with insulin resistance in some members of the population or whether the two abnormalities are causally linked. Here, I will develop the theme that insulin resistance causes B-cell dysfunction in susceptible individuals, using information from women who are at increased risk for T2DM by virtue of a clinical diagnosis of gestational diabetes.