Abstract

Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous decline in β-cell function in patients with type 2 diabetes. We studied longitudinal changes in β-cell function (follow-up of 5.2 years) in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes, using acute insulin response (AIR) and insulin sensitivity index (S_i) from a frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40–69 years. At baseline, decreasing levels of both S_i and AIR (either unadjusted or adjusted for S_i) mirrored deteriorating glucose tolerance status at baseline and at follow-up. A different pattern was found with respect to longitudinal changes; S_i declined in each glucose tolerance category, ranging from −0.81 ×10⁻⁴ min⁻¹ · μU⁻¹ · ml⁻¹ in NGT at baseline and NGT at follow-up (NGT/NGT) to −1.06 ×10⁻⁴ in NGT/diabetes, whereas the directional change in AIR principally determined the glucose tolerance status at follow-up. In NGT/NGT S_i decreased by 35% and AIR increased by 34%. Results were similar in each of the three ethnic groups. These data shed light on the natural course of β-cell function; over 5.2 years, mean insulin sensitivity declined in each glucose tolerance category. The change in AIR, however, principally determined glucose tolerance status at follow-up; NGT was maintained by a compensatory increase in insulin secretion. Failure to increase insulin secretion led to IGT, and a decrease in insulin secretion led to overt diabetes. This data may have important implications for the prevention and treatment of type 2 diabetes.