Importance of substrate competition in the mechanism of insulin resistance in man

Abstract

Carbohydrate (CHO) oxidation induced by a glucose or fructose (0.5 g/kg × h) infusion over two hours was compared for 160 minutes by means of continuous indirect calorimetry in seven normal subjects without or with a concomitant infusion of Intralipid, a neutral fat emulsion. The glucose infusion was accompanied by a rise over basal values in both glucose (99 ± 10 mg/dL) and insulin (36 ± 7 μU/mL) plasma levels, with a further rise of both curves during the Intralipid infusion (140 ± 7 mg/dL and 53 ± 12 μU/mL). By contrast, plasma glucose and insulin rose only minimally during the fructose infusion (3.5 ± 2.9 mg/dL and 5.3 ± 1.4 μU/mL, respectively, without Intralipid, and 10.6 ± 2.1 mg/dL and 9.6 ± 2.0 μU/mL with Intralipid). During the two-hour sugar infusion, a mean quantity of 68.7 g glucose or fructose was infused. The total CHO oxidation was 15.6 ± 1.2 g for glucose and 21.6 ± 2.6 for fructose infusion for the 160 minutes of the test. During the Intralipid infusion, CHO oxidation was inhibited with values of 5.9 ± 1.3 g for glucose ( P < .005) and 13.8 ± 1.8 g ( P < .05) for fructose infusion. Lipid oxidation was increased in both cases during the Intralipid infusion. These results show that the lipid-induced inhibition of CHO oxidation observed with glucose infusion also occurs to some extent with fructose, suggesting that insulin might not be primarily involved. They suggest a metabolic origin for insulin resistance during elevated fat metabolism.