Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance

Aims/hypothesis. We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). Methods. Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (phi(b), phi(d), phi(s), T-up, T-down), and insulin sensitivity (Si). Results. ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (phi(b)) and stimulated (phi(d), phi(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T-up) and -down (T-down) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5).min(-2) x 1) was lower in Obese-IGT compared to Controls, both during step-up (919 851 vs 3192 +/- 1185, P < 0.05) and step-down (1455 +/- 1203 vs 3625 691, p < 0.05) phases. Consistently, the product phi(s) x Si (10(-14).min(-2) . pmol(-1) x 1) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05). Conclusion/interpretation. Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.