Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial

The influence of diet macronutrient content on the cardiometabolic effects of weight loss in people with metabolically unhealthy obesity (prediabetes and hepatic steatosis) has important clinical implications. We evaluated the cardiometabolic effects of moderate (∼10%) weight loss induced by three popular diets with markedly different macronutrient composition (very-low-carbohydrate ketogenic, Mediterranean, and very-low-fat plant-forward). Weight loss increased muscle insulin sensitivity by ∼50% in all groups but caused a two-to-three-fold greater increase in hepatic insulin sensitivity in the very-low-carbohydrate group than the other groups (p < 0.001). Intrahepatic triglyceride content, hepatic de novo lipogenesis, glycated hemoglobin, and 24-h serial plasma glucose and insulin decreased most in the very-low-carbohydrate group. There were no differences among groups in LDL-cholesterol, apolipoprotein B, or 24-h plasma triglyceride concentrations. These results demonstrate that a very-low-carbohydrate diet has greater cardiometabolic benefits, particularly in hepatic metabolic function, than matched 10% weight loss induced by a Mediterranean or very-low-fat diet in people with metabolically unhealthy obesity. This study was registered at ClinicalTrials.gov (NCT02706262).