Incretin action maintains insulin secretion, but not hepatic insulin action, in people with impaired fasting glucose.

Aims To determine whether altered GLP-1 activity contributes to the abnormal endogenous glucose production (EGP) and insulin secretion characteristic of people with impaired fasting glucose (IFG). Methods People with IFG (n = 10) and normal glucose tolerance (NGT; n = 13) underwent assessment of EGP (via [6,6-2H2]-glucose infusion). Parameters of whole body insulin action and secretion were estimated by IVGTT and OGTT. Measures of EGP and insulin secretion were made before and after sitagliptin administration. Results EGP was not different at baseline (glucose Ra; 1.47 ± 0.08 vs. 1.46 ± 0.05 mg/kg/min, IFG vs. NGT, p = 0.93). However, when differences in circulating insulin were accounted for (EGPXSSPI; 20.2 ± 2.1 vs. 14.4 ± 1.0AU, vs. NGT, p = 0.03) the hepatic insulin resistance index was significantly higher in IFG. Baseline insulin action (Si; 2.3 ± 0.1 × 10−4/μU/ml vs. 3.5 ± 0.4 × 10−4/μU/ml, p = 0.01, IFG vs. NGT) and secretion (DI; 587 ± 81 × 10−4/min vs. 1171 ± 226 × 10−4/min, p = 0.04, IFG vs. NGT) were impaired in IFG when evaluated by the IVGTT, but not by OGTT (insulin sensitivity 4.52 ± 1.08 × 10−4 dl/kg/min vs. 6.73 ± 1.16 × 10−4 dl/kg/min, IFG vs. NGT, p = 0.16; indices of basal (Φb), static (Φs), dynamic (Φd), and total (Φt) insulin secretion, p > 0.07). Sitagliptin did not change EGP or insulin secretion in either group. Conclusions Incretin action maintained insulin secretion, but not hepatic insulin action, in people with IFG.