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The Effects of Carbohydrate Variation in Isocaloric Diets on Glycogenolysis and Gluconeogenesis in Healthy Men¹

Departments of Endocrinology and Metabolism (P.H.B., A.M.P.A., H.P.S.) Clinical Chemistry (M.T.A., E.E.), and Biochemistry (A.J.M.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam; Center for Liver, Digestive, and Metabolic Diseases, Academic Hospital Groningen (F.K.), 9713 GZ Groningen; and Departments of Internal Medicine (H.P.) and Endocrinology (P.H.B., J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: P. H. L. T. Bisschop, M.D., Department of Endocrinology and Metabolism (F5), Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: p.h.bisschop{at}amc uva.nl.

To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets were eucaloric and provided 15% of energy as protein. Postabsorptive glucose production was measured by infusion of [6,6-²H₂]glucose, and fractional gluconeogenesis was measured by ingestion of ²H₂O. Postabsorptive glucose production rates were 13.0 ± 0.7, 11.4 ± 0.4, and 9.7 ± 0.4 µmol/kg·min after high carbohydrate, control, and very low carbohydrate diets, respectively (P < 0.001 among the three diets). Gluconeogenesis was about 14% higher after the very low carbohydrate diet (6.3 ± 0.2 µmol/kg·min; P = 0.001) compared to the control diet, but was not different between the high carbohydrate and control diets (5.5 ± 0.3 vs. 5.5 ± 0.2 µmol/kg·min). The rates of glycogenolysis were 7.5 ± 0.5, 5.9 ± 0.3, and 3.4 ± 0.3 µmol/kg·min, respectively (P < 0.001 among the three diets).

We conclude that under eucaloric conditions in healthy subjects, dietary carbohydrate content affects the rate of postabsorptive glucose production mainly by modulation of glycogenolysis. In contrast, dietary carbohydrate content affects the postabsorptive rate of gluconeogenesis minimally, as evidenced by only a slight increase in gluconeogenesis during severe carbohydrate restriction.

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