Delayed Insulin Responses to Rising and Falling Glucose in Subjects With Impaired Glucose Tolerance

Even before the diagnosis of Diabetes, those with IGT suffer with delayed beta cell response.

It was hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT).

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 (f_b, f_d, f_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 (f_b) and stimulated (f_d, f_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 × Si (10^-5·min^-2 × l) 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 f_s × Si (10-14·min^-2 · pmol^-1 × l) was lower in Obese-IGT than in control subjects (27.6 ± 25.4 vs 103.1 ± 20.2, P < 0.05).

From the results it was concluded that, 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.