Epidemiology and Prevention Effects of Weight Loss and Long-Term Weight Maintenance With Diets Varying in Protein and Glycemic Index on Cardiovascular Risk Factors The Diet, Obesity, and Genes (DiOGenes) Study: A Randomized, Controlled Trial

Background—We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes). Methods and Results—DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (Ϫ11.23 kg; 95% confidence interval, Ϫ11.54 to Ϫ10.92; PϽ0.001) reduced high-sensitivity C-reactive protein (Ϫ1.15 mg/L; 95% confidence interval, Ϫ1.30 to Ϫ0.41; PϽ0.001), low-and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was Ϫ0.46 mg/L greater (95% confidence interval, Ϫ0.79 to Ϫ0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (PϽ0.001). Groups on low-protein diets achieved a Ϫ0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, Ϫ0.59 to Ϫ0.17) than those on high-protein diets (PϽ0.001), whereas lipid profiles and blood pressure were not differently affected. Conclusions—This large-scale intervention study clearly separates weight loss from dietary composition–related effects. Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults. D ietary composition significantly influences cardiovas-cular risk factors and outcomes under ad libitum (free access to food/diets and type of nutrients) conditions, as reported in several observational and intervention studies. 1– 4 Although the role of different types of fat has been addressed in numerous studies, the roles of carbohydrate quality and of protein intake are less well established. Although a high glycemic index is related to postprandial hyperglycemia and a greater release of insulin, which may lead to an unfavorable impact on other cardiovascular risk factors, 5 a lower glycemic index was correlated with favorable effects on blood lipids, particularly low-density lipoprotein cholesterol and triglycerides and a lower level of high-sensitivity C-reactive protein (hsCRP) as a marker of low-grade inflammation. 6 – 8 hsCRP was shown to correlate with the risk of cardiovascular events and type 2 diabetes mellitus in prospective studies. 9,10 Dietary protein improves postprandial satiety, 11 and higher intakes may be associated with improved weight maintenance. 12 There …