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Original Research Communication |
1 From the Departments of Endocrinology and Metabolism, Clinical Chemistry Laboratory of Endocrinology, and Biochemistry, Academic Medical Center, University of Amsterdam; the Center for Liver, Digestive and Metabolic Diseases, Academic Hospital Groningen, Groningen, Netherlands; and the Departments of Internal Medicine and Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
Background: A high dietary fat intake is involved in the pathogenesis of insulin resistance.
Objective: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity.
Design: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: 
190 pmol/L).
Results: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 ± 0.3 µmol•kg-1•min-1; P < 0.05) than after the IFIC and LFHC diets (1.7 ± 0.3 and 1.2 ± 0.4 µmol•kg-1•min-1, respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 ± 5.1 to 20.6 ± 1.9 to 26.2 ± 2.9 µmol•kg-1•min-1 (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 ± 0.8 compared with 13.4 ± 2.1 and 19.0 ± 2.1 µmol•kg-1•min-1, respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 ± 0.02 compared with 0.07 ± 0.01 and 0.05 ± 0.01 mmol/L, respectively (P < 0.05).
Conclusion: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.
Key Words: Glucose metabolism • insulin • dietary fat • dietary carbohydrate • euglycemic clamp • glucose turnover rate • men
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