Combined hypertriglyceridemic and insulin-glucose clamps for the characterization of substrate oxidation and plasma elimination of a long-chain triglyceride emulsion in healthy men

Abstract

This study examines the effect of glucose and insulin on the plasma elimination rate and oxidation of a fat emulsion by using indirect calorimetry in conjunction with lipid and insulin-glucose clamp techniques. Ten healthy subjects were studied on 2 occasions in a randomized, open, crossover study. On one occasion, a hypertriglyceridemic (HTG) clamp was administrated alone; and, on the other, HTG and insulin-glucose (IG) clamps were administrated simultaneously. During HTG clamps, serum triglyceride (TG) concentration was maintained at 4 mmol × L −1. During the IG clamp, insulin was administered at a rate of 20 mU × m −2 × min −1; and the glucose level was maintained at 7 mmol × L −1. Continuous indirect calorimetry was carried out throughout the study period. The infusion rate required to maintain stable serum TG concentrations did not differ between the 2 clamps. Mean free fatty acid concentration was lower during the HTG/IG than during the HTG clamp (0.40 ± 0.04 vs 0.82 ± 0.07 mmol × L −1; P < .001). However, the increases in β-OH-butyrate levels were significantly lower in the HTG/IG compared with the HTG clamp (0.09 ± 0.04 vs 0.55 ± 0.09 mmol × L −1; P < .001). Energy expenditure and the respiratory quotient were significantly higher at steady state in the HTG/IG than in the HTG clamp: 1.47 ± 0.06 vs 1.34 ± 0.04 kcal × min −1 ( P < .01) and 0.85 ± 0.01 vs 0.79 ± 0.01 ( P < .01), respectively. Insulin and glucose did not significantly change plasma TG disposal rate ( P = .0987) or total lipid oxidation ( P = .3204) in this metabolic situation with an abundant supply of both carbohydrates and lipids. β-OH-butyrate increased during both clamps, indicating an ongoing hepatic fatty oxidation despite the administration of glucose/insulin.