Individuals with prediabetes can be classified by fasting and glucose tolerance status. Previously we observed that elevated fasting Free Fatty Acids (FFA) are associated with Impaired Glucose Tolerance (IGT) and decreased β-cell function (quantified as Disposition Index (DI)) . Impaired Fasting glucose (IFG) is associated with further decreases in DI. To examine how changes in fasting FFA and glucose alter islet function, we studied 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 2 groups were matched for Body Mass Index (BMI: 32±3 vs. 31±2 kg/m2, NFG / NGT vs. IFG / IGT respectively, p = 0.87) . The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-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 hrs, Saline vs. Intralipid / glucose, p = 0.55) . In people with IFG / IGT, insulin also did not alter peak and integrated glucose concentrations (2.5 ± 0.1 vs. 2.5 ± 0.2 Mol per 5 hrs, Saline vs. Insulin, p = 0.39) . Changing overnight concentrations of glucose and FFA did not alter postprandial concentrations of insulin and C-peptide in either group. While fasting Endogenous Glucose Production (EGP) differed between groups (14 ± 1 vs. 18 ± 1 μmol/kg/min, NFG / NGT vs. IFG / IGT, p < 0.01) , intervention did not change fasting and nadir EGP. Peak and integrated meal appearance and DI were also unchanged by intervention in either group. We conclude that acute, overnight changes in FFA and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.
A.A.Welch: None. D.Schembri wismayer: None. A.M.Egan: None. R.A.Farahani: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk.
NIH DK 078646