Pathogenetic mechanisms of impaired glucose tolerance and type II diabetes in African-Americans - The significance of insulin secretion, insulin sensitivity, and glucose effectiveness

OBJECTIVE - To examine the significance of alterations in insulin sensitivity index (SI), glucose effectiveness (S-g), and beta-cell function in the pathogenesis of type II diabetes in African-Americans with varying degrees of glucose intolerance. RESEARCH DESIGN AND METHODS - A total of 154 African-Americans residing in Franklin County, Ohio, were studied. There were 101 subjects with normal glucose tolerance (NGT), 36 with impaired glucose tolerance (IGT), and 17 with type II diabetes. An oral glucose tolerance test (OGTT) was performed on each subject. S-I and S-g were measured by insulin-modified, frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS - The mean fasting and postprandial serum glucose levels were significantly greater in the diabetic groups when compared with the IGT and NGT groups. In contrast, while fasting serum insulin and C-peptide levels tended to be greater in the type II diabetic and IGT groups, the postprandial responses were blunted at 30 min in the IGT and type II diabetic soups when compared with the NGT group. The mean acute first-phase insulin release after intravenous glucose was blunted also in the IGT and ripe II diabetic groups when compared with the NGT group. The SI was significantly lower in the IGT (1.51 +/- 0.19) and type II diabetic (0.61 +/- 0.15) groups when compared with the NGT group (2.94 +/- 0.20 x 10(-4). min(-1) . U-1. ml(-1)). The S-I was not significantly different in the NGT (2.90 +/- 0.20), IGT (2.47 +/- 0.19), and the type II diabetic (2.35 +/- 0.15 x 10(-2)/min) groups. The glucose effectiveness at theoretical zero insulin concentration (GEZZ) followed similar patterns as the S-g. Furthermore, the basal insulin effect (BIE) was significantly lower in the IGT and type II diabetic groups compared with the: NGT group. In addition, the glucose decay constant (K-g) was significantly lower (P < 0.001) in the IGT (1.21 +/- 0.13) and the type II diabetic (1.07 +/- 0.12) groups when compared with the NGT group (2.03 +/- 0.10% per minute). CONCLUSIONS - Our present study demonstrates that African-American patients with IGT and mild type II diabetes have significant reduction in beta-cell function, insulin sensitivity, and BEI bur have normal and intact S-g and GEZI when compared with NGT subjects. We conclude the following: 1) a reduction in S-g does nor appear to pig a significant role in the pathogenetic mechanism of IGT and type II diabetes in African-American patients, and 2) the intact S-g in the IGT and type II diabetic groups could serve as a compensatory mechanism for hyperglycemia in African-Americans.