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A Low-Carbohydrate/High-Fat Diet Improves Glucoregulation in Type 2 Diabetes Mellitus by Reducing Postabsorptive Glycogenolysis

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

Address all correspondence and requests for reprints to: G. Allick, Department of Endocrinology and Metabolism (F5), Academic Medical Center, University of Amsterdam, P.O. BOX 22660, 1100 DD Amsterdam, The Netherlands. E-mail: g.allick{at}amc.uva.nl.

The aim of this study was to examine the mechanisms by which dietary carbohydrate and fat modulate fasting glycemia. We compared the effects of an eucaloric high-carbohydrate (89% carbohydrate) and high-fat (89% fat) diet on fasting glucose metabolism and insulin sensitivity in seven obese patients with type 2 diabetes using stable isotopes and euglycemic hyperinsulinemic clamps. At basal insulin levels glucose concentrations were 148 ± 11 and 123 ± 11 mg/dl (8.2 ± 0.6 and 6.8 ± 0.6 mmol/liter) on the high-carbohydrate and high-fat diet, respectively (P < 0.001), with insulin concentrations of 12 ± 2 and 10 ± 1 µIU/ml (82 ± 11 and 66 ± 10 pmol/liter) (P = 0.08). Glucose production was higher on the high-carbohydrate diet (1.88 ± 0.06 vs. 1.55 ± 0.05 mg/kg·min (10.44 ± 0.33 vs. 8.61 ± 0.28 µmol/kg·min) (P < 0.001) because of higher glycogenolysis. Gluconeogenic rates were not different between the diets. During the use of hyperinsulinemic euglycemic clamps, insulin-mediated suppression of glucose production and stimulation of glucose disposal were not different between the diets. Free fatty concentrations were suppressed by 89 and 62% (P < 0.0001) on the high-carbohydrate and high-fat diet, respectively. We conclude that short-term variations in dietary carbohydrate to fat ratios affect basal glucose metabolism in people with type 2 diabetes merely through modulation of the rate of glycogenolysis, without affecting insulin sensitivity of glucose metabolism.

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