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 impaired glucose tolerance (IGT) or early NIDDM. To assess insulin secretion at these critical stages, we measured the first-phase insulin response (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal glucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7.8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and insulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although as a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired insulin secretion. The first-phase response to glucose was markedly reduced in absolute terms (P < .001), but all secretion indices were impaired relative to the degree of insulin resistance (P = .05 to P < .0001). These results suggest that in Pima Indians, impairment of insulin secretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, seems intact, although a subtle defect in the first-phase insulin response to glucose could not be ruled out in this study. Glucose sensing for 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.