Clinical Science| Volume 61, ISSUE 3, P358-365, March 2012

Download started.


A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves β-cell function in individuals with impaired fasting glucose

Published:September 26, 2011DOI:


      The objective was to examine the effects of diet macronutrient composition on insulin sensitivity, fasting glucose, and β-cell response to glucose. Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL) and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass index, 32.5 ± 4.2 kg/m2) men and women. For 8 weeks, participants were provided with eucaloric diets, either higher carbohydrate/lower fat (55% carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39). Insulin sensitivity and β-cell response to glucose (basal, dynamic [PhiD], and static) were calculated by mathematical modeling using glucose, insulin, and C-peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG. After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this pattern was not observed among NGT. Within IFG, fasting glucose at baseline and the change in fasting glucose over the intervention were inversely associated with baseline PhiD (−0.40, P < .05) and the change in PhiD (−0.42, P < .05), respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and lower fasting glucose and greater glucose-stimulated insulin secretion in individuals with IFG. If confirmed, these results may have an impact on dietary recommendations for overweight individuals with and without IFG.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cowie C.C.
        • Rust K.F.
        • Byrd-Holt D.D.
        • et al.
        Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population.
        Diabetes Care. 2006; 29: 1263-1268
        • Wild S.
        • Roglic G.
        • Green A.
        • et al.
        Global prevalence of diabetes.
        Diabetes Care. 2004; 27: 1047-1053
        • DeFronzo R.A.
        Pathogenesis of type 2 diabetes mellitus.
        Med Clin North Am. 2004; 88: 787-835
        • Rana J.S.
        • Li T.Y.
        • Manson J.E.
        • et al.
        Adiposity compared with physical inactivity and risk of type 2 diabetes in women.
        Diabetes Care. 2007; 30: 53-58
        • Wilson P.W.F.
        • Meigs J.B.
        • Sullivan L.
        • et al.
        Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study.
        Arch Intern Med. 2007; 167: 1068-1074
        • Unwin N.
        • Shaw J.
        • Zimmet P.
        • et al.
        Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention.
        Diabet Med. 2002; 19: 708-723
        • Abdul-Ghani M.A.
        • Tripathy D.
        • DeFronzo R.
        Contribution of B-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose.
        Diabetes Care. 2006; 29: 1130-1139
        • Abdul-Ghani M.
        • DeFronzo R.
        Pathogenesis of insulin resistance in skeletal muscle.
        J Biomed Biotechnol. 2010; : 2010
        • Jani R.
        • Molina M.
        • Matsuda M.
        • et al.
        Decreased non–insulin-dependent glucose clearance contributes to the rise in fasting plasma glucose in the nondiabetic range.
        Diabetes Care. 2008; 31: 311-315
        • Godsland I.F.
        • Jeffs J.A.R.
        • Johnston D.G.
        Loss of beta cell function as fasting glucose increases in the non-diabetic range.
        Diabetologia. 2004; 47: 1157-1166
        • Rossetti L.
        • Shulman G.I.
        • Zawalich W.
        • et al.
        Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats.
        J Clin Invest. 1987; 80: 1037-1044
        • Meyer J.
        • Sturis J.
        • Katschinski M.
        • et al.
        Acute hyperglycemia alters the ability of the normal beta-cell to sense and respond to glucose.
        Am J Physiol (Endocrinology and Metabolism). 2002; 282: E917-E922
        • Gastaldelli A.
        • Ferrannini E.
        • Miyazaki Y.
        • et al.
        Beta-cell dysfunction and glucose intolerance: results from the San Antonio Metabolism (SAM) study.
        Diabetologia. 2004; 47: 31-39
        • Boden G.
        • Lebed B.
        • Schatz M.
        • et al.
        Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects.
        Diabetes. 2001; 50: 1612-1617
        • Robertson R.P.
        • Harmon J.
        • Tran P.O.T.
        • et al.
        Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes.
        Diabetes. 2004; 53: S119-S124
        • Eizirik D.L.
        • Cnop M.
        ER stress in pancreatic beta cells: the thin red line between adaptation and failure.
        Sci Signal. 2010; 3: e7
        • Solomon T.P.
        • Haus J.M.
        • Kelly K.R.
        • et al.
        A low–glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans.
        Am J Clin Nutr. 2010; 92: 1359-1368
        • Acheson K.J.
        Carbohydrate for weight and metabolic control: where do we stand?.
        Nutrition. 2010; 26: 141-145
        • Harris J.A.
        • Benedict F.G.
        A biometric study of basal metabolism in man.
        Carnegie Institution, Washington DC1919
        • Douglas C.A.
        • Gower B.A.
        • Darnell B.E.
        • et al.
        Role of diet in the treatment of PCOS.
        Fertil Steril. 2006; 85: 679-688
        • Goree L.L.
        • Chandler-Laney P.C.
        • Ellis A.C.
        • et al.
        Dietary macronutrient composition affects beta-cell responsiveness but not insulin sensitivity.
        Am J Clin Nutr. 2011; ([epub ahead of print])
        • Breda E.
        • Cavaghan M.K.
        • Toffolo G.
        • et al.
        Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity.
        Diabetes. 2001; 50: 150-158
        • Cobelli C.
        • Toffolo G.
        • Dalla Man C.
        • et al.
        Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.
        Am J Physiol (Endocrinology and Metabolism). 2007; 293: E1-E15
        • Peter A.
        • Kantartzis K.
        • Machann J.
        • et al.
        Relationships of circulating sex hormone–binding globulin with metabolic traits in humans.
        Diabetes. 2010; 59: 3167-3173
        • Gastaldelli A.
        • Cusi K.
        • Pettiti M.
        • et al.
        Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects.
        Gastroenterology. 2007; 133: 496-506
        • McGarry J.D.
        Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.
        Diabetes. 2002; 51: 7-18
        • Boden G.
        Fatty acids in the pathogenesis of insulin resistance and NIDDM.
        Diabetes. 1996; 45: 3-10
        • Shulman G.I.
        Cellular mechanisms of insulin resistance.
        J Clin Invest. 2000; 106: 171-176
        • de Koning L.
        • Fung T.T.
        • Liao X.
        • et al.
        Low-carbohydrate diet scores and risk of type 2 diabetes in men.
        Am J Clin Nutr. 2011; 93: 844-850
        • Knowler W.C.
        • Barrett-Connor E.
        • Fowler S.E.
        • et al.
        Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
        N Engl J Med. 2002; 346: 393-403
        • Nettleton J.A.
        • McKeown N.M.
        • Kanoni S.
        • et al.
        Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent.
        Diabetes Care. 2010; 33: 2684-2691
        • Lopez S.
        • Bermudez B.
        • Pacheco Y.M.
        • et al.
        Distinctive postprandial modulation of beta cell function and insulin sensitivity by dietary fats: monounsaturated compared with saturated fatty acids.
        Am J Clin Nutr. 2008; 88: 638-644
        • American Diabetes Association
        Standards of medical care in diabetes—2011.
        Diabetes Care. 2011; 34: S11-S61
        • Buse J.B.
        • Ginsberg H.N.
        • Bakris G.L.
        • et al.
        Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association.
        Circulation. 2007; 115: 114-126
        • Appel L.J.
        • Moore T.J.
        • Obarzanek E.
        • et al.
        A clinical trial of the effects of dietary patterns on blood pressure.
        N Engl J Med. 1997; 336: 1117-1124
        • de Koning L.
        • Chiuve S.E.
        • Fung T.T.
        • et al.
        Diet-quality scores and the risk of type 2 diabetes in men.
        Diabetes Care. 2011; 34: 1150-1156