Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of beta-cell function and glucose metabolism in subjects without diabetes

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased beta-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and beta-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 +/- 0.1 vs. 2.0 +/- 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall beta-cell function quantified by the Disposition Index was unchanged, the dynamic component of beta-cell responsivity (phi(d)) was decreased by Intralipid and glucose infusion (9 +/- 1 vs. 16 +/- 3 10(-9), P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of beta-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes. NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on beta-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the beta-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the beta-cell.

Automated summary

Changes in overnight concentrations of free fatty acids (FFAs) and glucose do not affect islet function or glucose metabolism. Elevated FFAs and glucose levels impair the dynamic component of the beta-cell response to glucose.