On the interplay between insulin secretion and sensitivity as determinants of glucose tolerance

Both insulin secretion and sensitivity have been claimed to be the main characteristics in the determination of future deterioration in glucose tolerance. In this cross-sectional study insulin secretion and insulin sensiturity were determined in 228 subjects with varying degrees of glucose tolerance. Insulin secretion was measured in an intravenous glucose tolerance test (IVGTT) and insulin sensitivity by the hyperinsulinaemic euglycaemic clamp test. Both the early insulin response in the IVGTT (increment) and the glucose disposal rate in the clamp test (M-value) were found to be related hyperbolically to fasting glucose (r = -0.63 and -0.66, respectively; both P < 0.0001) and in a second-order polynomial manner to the glucose disappearance rate (k-value) in the IVGTT (r = 0.53 and 0.48, respectively; both P < 0.0001). Multiple regression analysis showed the insulin increment in the IVGTT and the M-value in the clamp test to be equally important determinants of glucose tolerance, together explaining about 50% of the variation in fasting glucose and the k-value in the IVGTT. In conclusion, in this cross-sectional study insulin secretion and sensitivity studied over a broad range of glucose tolerance were found to be of almost equal importance in the determination of glucose tolerance. However, low levels of insulin increment in the IVGTT were more often associated with glucose intolerance than was a low insulin sensitivity.