INSULIN-SECRETION AND INSULIN SENSITIVITY IN PEOPLE WITH IMPAIRED GLUCOSE-TOLERANCE

To assess the roles of pancreatic beta-cell (beta-cell) dysfunction an d insulin resistance in the pathogenesis of non-insulin dependent diab etes mellitus, we used euglycaemic hyperinsulinaemic and hyperglycaemi c clamps to compare insulin secretion and insulin sensitivity in Cauca sian individuals of European ancestry with either normal glucose toler ance (NGT) or impaired glucose tolerance (IGT). Both groups were caref ully matched for age, gender, obesity and body fat distribution. Durin g 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 w hile their insulin sensitivity index (0.126 +/- 0.012 mu mol kg(-1) pM (-1)) was not significantly different from that of NGT (0.144 +/- 0.01 2 mu mol kg(-1) min(-1) pM(-1)), p = 0.69). Similarly, during the eugl ycaemic hyperinsulinaemic clamps, the insulin sensitivity index of the IGT (0.076 +/- 0.005 mu mol kg(-1) min(-1) pM(-1)) was not significan tly different from that of the NGT (0.086 +/- 0.007 mu mol 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 prim ary genetic factor predisposing to the development of non-insulin depe ndent diabetes mellitus in Caucasians of European ancestry.