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Effects of overnight fasting milieu on indices of β-cell function and glucose metabolism in subjects without diabetes

Am J Physiol Endocrinol Metab. 2023 Jun 7. doi: 10.1152/ajpendo.00043.2023. Online ahead of print.

ABSTRACT

OBJECTIVE: Elevated fasting free fatty acids (FFA) are associated with Impaired Glucose Tolerance (IGT) and decreased β-cell function (quantified as Disposition Index (DI)). We sought to examine how changes in fasting FFA and glucose alter islet function.

METHODS: We studied 10 subjects with Normal Fasting Glucose (NFG) and Normal Glucose Tolerance (NGT) on 2 occasions. On one occasion, Intralipid® and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied 7 subjects with IFG/IGT on 2 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 β-cell function.

RESULTS: 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). While overall β-cell function quantified by the Disposition Index was unchanged, the dynamic component of β-cell responsivity (fd) 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 β-cell function. Endogenous glucose production and glucose disappearance was also unchanged in both groups.

CONCLUSIONS: We conclude that acute, overnight changes in FFA and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.

PMID:37285600 | DOI:10.1152/ajpendo.00043.2023

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