Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM

To further explore the role of the beta-cell as a pathogenic factor behind non-insulin-dependent diabetes mellitus (NIDDM), insulin secretion at modest hyperglycemia was examined in 15 healthy first-degree relatives of NIDDM patients and 13 anthropometrically and age-matched controls. The oral glucose tolerance test was normal in all, but the relatives had impaired insulin-stimulated glucose uptake (P < 0.05). During a constant intravenous glucose infusion we performed a time-series analysis of serum insulin in samples obtained at 1-min intervals for 75 min (60-135 min). The recently introduced scale- and model-independent statistic approximate entropy (ApEn) and the coefficient of variation for a 6- (9 and 15) point moving average (MA) were applied to test regularity and stationarity, respectively, of insulin secretion. Both ApEn and 6-point MA were able to significantly discern the insulin time series of the two groups (P < 0.05), demonstrating a higher degree of irregularity and nonstationarity among the offspring. Moreover, when the two complementary sets of statistics were combined into a single "index of nonpulsatility," an even more notable distinction was available (P < 0.01). No relationship was found between altered insulin secretion and insulin resistance. In conclusion, this experimental and statistical model demonstrates that the stimulated insulin secretion of glucose-tolerant relatives of NIDDM patients is characterized by disorderliness. Whether the model can predict the risk for developing a clinically important beta-cell dysfunction remains to be clarified.