Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.