Insulin Secretion and Insulin Sensitivity in People with Impaired Glucose Tolerance

To assess the roles of pancreatic beta-cell (beta-cell) dysfunction and insulin resistance in the pathogenesis of non-insulin dependent diabetes mellitus, we used euglycaemic hyperinsulinaemic and hyperglycaemic clamps to compare insulin secretion and insulin sensitivity in Caucasian individuals of European ancestry with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Both groups were carefully matched for age, gender, obesity and body fat distribution. During the hyperglycaemic clamps, IGT had significantly lower first phase (650 +/- 60 vs 992 +/- 92 pmol l-1, p = 0.001) and second phase (231 +/- 24 vs 326 +/- 21 pmol l-1, p < 0.001) plasma insulin responses while their insulin sensitivity index (0.126 +/- 0.012 mumol kg-1 pM-1) was not significantly different from that of NGT (0.144 +/- 0.012 mumol kg-1 min-1 pM-1), p = 0.69). Similarly, during the euglycaemic hyperinsulinaemic clamps, the insulin sensitivity index of the IGT (0.076 +/- 0.005 mumol kg-1 min-1 pM-1) was not significantly different from that of the NGT (0.086 +/- 0.007 mumol kg-1 min-1 pM-1), p = 0.28. We conclude that since beta-cell dysfunction is already evident in people with impaired glucose tolerance but insulin resistance is not, impaired insulin secretion is most likely the primary genetic factor predisposing to the development of non-insulin dependent diabetes mellitus in Caucasians of European ancestry.