Plasma Nonesterified Fatty Acid Intolerance and Hyperglycemia Are Associated with Intravenous Lipid-Induced Impairment of Insulin Sensitivity and Disposition Index

Context: It is currently unclear why susceptibility to lipid-induced impairment of beta-cell function varies in different populations. Objective: The aim of the study was to determine whether mild hyperglycemia may be associated with nonesterified fatty acid (NEFA) intolerance and increased iv lipid-induced lipotoxic effect on the beta-cell. Design and Setting: The study consisted of an experimental design with control group conducted at an academic clinical research center. Participants: Twenty-six overweight or obese individuals (12 with normal glucose tolerance, nine with impaired glucose tolerance or type 2 diabetes, and five subjects who previously had impaired glucose tolerance or type 2 diabetes but at the time of study had normal glucose tolerance after biliopancreatic diversion). Interventions: We assessed insulin sensitivity (SI) and beta-cell function [insulin disposition index (DI)] after an overnight iv infusion of heparin + Intralipid (HI) vs. normal saline for 16 h using a stepwise, incremental iv glucose infusion followed by a hyperglycemic clamp. Main Outcome Measures: We measured SI, DI, HI-induced change in plasma NEFA, and its association with HI-induced change in SI and DI. Results: HI resulted in significant reduction in SI and DI across the three groups of participants. HI-induced elevation of plasma NEFA was higher in hyperglycemic vs. normoglycemic groups. Both fasting glucose level and the magnitude of HI-induced NEFA elevation were associated with the reduction in S-I (P = 0.007 and P = 0.01, respectively) and DI (P = 0.001 and P = 0.007, respectively). Conclusion: Mild hyperglycemia and NEFA intolerance to iv lipid are associated with susceptibility to lipid-induced reduction in SI and DI. (J Clin Endocrinol Metab 95: 1256-1264, 2010)