IN-VIVO BETA-CELL FUNCTION AT THE TRANSITION TO EARLY NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Impaired insulin secretion occurs at some stage in the development of non-insulin dependent diabetes mellitus (NIDDM), possibly during impai red glucose tolerance (IGT) or early NIDDM. To assess insulin secretio n at these critical stages, we measured the first-phase insulin respon se (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal g lucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7. 8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and i nsulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although a s a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired ins ulin secretion. The first-phase response to glucose was markedly reduc ed in absolute terms (P < .001), but all secretion indices were impair ed relative to the degree of insulin resistance (P = .05 to P < .0001) . These results suggest that in Pima Indians, impairment of insulin se cretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, s eems intact, although a subtle defect in the first-phase insulin respo nse to glucose could not be ruled out in this study. Glucose sensing f or first-phase secretion may be one of the early secretory defects in the progression of glucose intolerance and seems to be critical at the transition from IGT to early NIDDM. Copyright (C) 1995 by W.B. Saunde rs Company