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DIABETES, OBESITY AND METABOLISM review article Glucose Intolerance Abnormal Endothelial Uric Acid Dysfunction Metabolism Insulin Resistance Inflammation Dyslipidemia Prothrombotic Hemodynamic Factors ChangesFigure 1. Disease-related consequences of insulin resistance .Table 1. Risk factors for insulin resistance . weight on the high-carbohydrate/low-fat diet than the low- carbohydrate/high-fat diet (13.5 vs. 6.8%) .Overweight/obesity A similar 24-week pilot study showed comparable results.Sedentary lifestyle Thirty-two overweight adults had insulin values measuredNon-Caucasian ethnicity 30 min after a 75-g oral glucose tolerance test, and were assignedFamily history of type 2 diabetes, hypertension or cardiovascular disease to either a high-glycaemic load diet or a low-glycaemic loadHistory of gestational diabetes or glucose intolerance diet. The composition of the high-glycaemic load diet wasHistory of cardiovascular disease, hypertension, polycystic ovarian 60% carbohydrate, 20% protein, 20% fat, 15 g ﬁbre/1000 kcal, syndrome, nonalcoholic fatty liver disease or acanthosis nigricans mean estimated daily glycaemic index of 86 and a glycaemic load of 116 g/1000 kcal. The composition of the low-glycaemic load diet was 40% carbohydrate, 30% protein, 30% fat, 15 gloss. In individuals with a high insulin response to glucose, a ﬁbre/1000 kcal, mean estimated daily glycaemic index of 53high-glycaemic load results in increased postprandial insulin and a glycaemic load of 45 g/1000 kcal. Subjects with highlevels, favouring fatty acid uptake, inhibition of lipolysis and insulin secretion lost more weight on a low-glycaemic loadenergy storage. High-glycaemic-load diets also result in a lower diet compared to a high-glycaemic load diet (p = 0.047).glucose nadir and increases in counterregulatory hormones,which may cause hunger and overeating . In addition, low-glycaemic load subjects with high insulin In a 16-week clinical study, 12 insulin-sensitive and 9 secretion lost more weight than low-glycaemic load subjectsinsulin-resistant obese women were randomized to either with low insulin secretion (p = 0.027) .a high-carbohydrate/low-fat (60% carbohydrates and 20% In an 18-month clinical trial, 73 obese young adults werefat) diet or a low-carbohydrate/high-fat (40% carbohydrates randomized to either a low-glycaemic load (40% carbohydratesand 40% fat) diet. Insulin-resistant women lost 13.4% of and 35% fat) diet or a low-fat (55% carbohydrate and 20% fat)their initial body weight on the low-carbohydrate/high-fat diet. Serum insulin concentrations at 30 min after a 75-g dose ofplan, compared to 8.5% on the high-carbohydrate/low-fat oral glucose were measured at baseline. For those subjects withplan. Interestingly, insulin-sensitive women lost more high insulin secretion, the low-glycaemic load diet resulted inVolume 13 No. 3 March 2011 doi:10.1111/j.1463-1326.2010.01328.x 205
review article DIABETES, OBESITY AND METABOLISMgreater weight loss (5.8 vs. 1.2 kg, p = 0.004) than the low-fat in both normal and hypertriglyceridemic subjects [15,16].diet . It is therefore reasonable for health care practitioners to Most recently, 45 obese insulin-resistant female subjects were recommend that individuals with insulin resistance avoid low-randomized to either a low-fat (60% carbohydrate, 20% fat and fat/high-carbohydrate diets, unless there is concurrent weight20% protein) diet or a low-carbohydrate (45% carbohydrate, loss .35% fat and 20% protein) diet. Both dietary interventionsutilized prepared calorie-controlled meals. After 12 weeks,the low-fat group lost 7.34 kg, compared to 9.33 kg in the Conﬂict of Interestlow-carbohydrate group (p = 0.04) . Dr Lee and Dr Fujioka designed the study, did data collection In contrast, 31 obese women underwent insulin resistance and analysis. Dr Lee wrote the manuscript. Both the authorstesting (somatostatin/insulin/glucose infusion, as well as have no competing interests.postprandial insulin measurements) and were placed on ahypocaloric (1000 kcal deﬁcit) diet composed primarily of Referencesliquid nutritional supplements. There was no correlationbetween insulin resistance and the amount of weight loss 1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults. JAMA 2010; 303: 235–241.at 2 months for the 20 subjects who successfully lost weight.The ten insulin-resistant subjects lost 9.3 ± 0.5 kg, while the 2. Dansinger ML, Gleason JA, Grifﬁth JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss andten insulin-sensitive subjects lost 9.1 ± 0.3 kg. As for the heart disease risk reduction: a randomized trial. JAMA 2005; 293: 43–53.11 subjects who were unsuccessful in losing weight, six were 3. Nordmann AJ, Nordmann A, Briel M et al. Effects of low-carbohydrate vsinsulin-sensitive and ﬁve were insulin-resistant . low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis A longer study by the same investigators utilized a of randomized controlled trials. Arch Intern Med 2006; 166: 285–293.standard (500 kcal deﬁcit) hypocaloric diet and the weight 4. Einorn D, Reaven GM, Cobin RH et al. ACE position statement on the insulinloss medication sibutramine, and found similar results. resistance syndrome. Endocr Pract 2003; 9: 240–252.Among 24 obese women provided a dietician-prescribed 5. Stern SE, Williams K, Ferrannini E, DeFronzo RA, Bogardus C, Stern MP.plan and sibutramine 15 mg/day over 4 months, there was Identiﬁcation of individuals with insulin resistance using routine clinicalno difference in weight loss between the insulin-resistant measurements. Diabetes 2005; 54: 333–339.and insulin-sensitive groups. The 13 insulin-resistant subjects 6. Ludwig DS. The glycemic index: physiological mechanisms relatinglost 8.6 ± 1.3 kg, while the 11 insulin-sensitive subjects to obesity, diabetes, and cardiovascular disease. JAMA 2002; 287:lost 7.9 ± 1.4 kg. The insulin suppression test, utilizing 2414–2423.somatostatin/insulin/glucose infusions, was again used to 7. Cornier MA, Donahoo WT, Pereira R et al. Insulin sensitivity determinesdetermine insulin sensitivity and insulin resistance . the effectiveness of dietary macronutrient composition on weight loss in Finally, a landmark 2-year trial examined the effects of diets obese women. Obes Res 2005; 13: 703–709.with a variety of macronutrient compositions, and found no 8. Pittas AG, Das SK, Hajduk CL et al. A low-glycemic load diet facilitatesdifference in weight loss. Eight hundred and eleven overweight greater weight loss in overweight adults with high insulin secretion butand obese adults were randomized to one of four diets; fat not in overweight adults with low insulin secretion in the CALERIE trial.content ranged between 20 and 40%, protein content ranged Diabetes Care 2005; 28: 2939–2941.between 15 and 25%, and carbohydrate content ranged between 9. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of35 and 65%. Group and individual sessions were used to provide a low-glycemic load vs low-fat diet in obese young adults. JAMA 2007;750 kcal deﬁcit meal plans. Weight loss was similar among all 297: 2092–2102.four diets (3–4 kg), and there was no difference between the 10. Plodkowski RA, St Jeor ST, Nguyen QT, Fernandez GCJ, Dahir VB. Effect ofhighest carbohydrate diet and the lowest carbohydrate diet. diet composition on weight loss in insulin resistant people. Endocr Rev 2010; 31: S31.While no formal testing for insulin resistance was performedin the study subjects, the presence of metabolic syndrome 11. McLaughlin T, Abbasi F, Carantoni M, Schaaf P, Reaven G. Differences in insulin resistance do not predict weight loss in hypocaloric diets in healthydecreased in all four groups after 2 years, from 32% to obese women. J Clin Endocrinol Metab 1999; 84: 578–581.approximately 20% . 12. McLaughlin T, Abbasi F, Kim HS, Lamendola C, Schaaf P, Reaven G. Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women. Metabolism 2001; 50: 795–800.Recommendations 13. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets withThe prevailing consensus is that a variety of dietary approaches different compositions of fat, protein, and carbohydrates. NEJM 2009; 360:will result in weight and cardiac risk factor reduction, with 859–873.greater adherence producing greater results [2,13,14]. How- 14. Rock CL, Pakiz B, Flatt SW, Quintana EL. Randomized trial of a multifacetedever, individuals who have been identiﬁed as insulin-resistant commercial weight loss program. Obesity 2007; 15: 939–949.may derive additional short-term weight loss results from a 15. Coulston AM, Liu GC, Reaven GM. Plasma glucose, insulin and lipidlow-carbohydrate diet compared to a low-fat diet. A low- responses to high-carbohydrate low-fat diets in normal humans.carbohydrate approach in such patients would also be less Metabolism 1983; 32: 52–56.likely to exacerbate the existing hyperinsulinemic state, as stud- 16. Liu GC, Coulston AM, Reaven GM. Effect of high-carbohydrate low-fat dietsies have showed that a high-carbohydrate (60% of calories) diet on plasma glucose, insulin and lipid responses in hypertriglyceridemicadversely affected postprandial insulin and triglyceride levels humans. Metabolism 1983; 32: 750–753.206 Lee and Fujioka Volume 13 No. 3 March 2011