Effects of Low-Fat, Mediterranean, or Low-Carbohydrate Weight Loss Diets on Serum Urate and Cardiometabolic Risk Factors: A Secondary Analysis of the Dietary Intervention Randomized Controlled Trial (DIRECT)

OBJECTIVE Weight loss diets may reduce serum urate (SU) by lowering insulin resistance while providing cardiometabolic benefits, something urate-lowering drugs have not shown in trials. We aimed to examine the effects of weight loss diets on SU and cardiometabolic risk factors. RESEARCH DESIGN AND METHODS This secondary study of the Dietary Intervention Randomized Controlled Trial (DIRECT) used stored samples from 235 participants with moderate obesity randomly assigned to low-fat, restricted-calorie (n= 85); Mediterranean, restricted-calorie (n= 76); or low-carbohydrate, non-restricted-calorie (n= 74) diets. We examined SU changes at 6 and 24 months overall and among those with hyperuricemia (SU >= 416 mu mol/L), a relevant subgroup at risk for gout. RESULTS Among all participants, average SU decreases were 48 mu mol/L at 6 months and 18 mu mol/L at 24 months, with no differences between diets (P> 0.05). Body weight, HDL cholesterol (HDL-C), total cholesterol:HDL-C ratio, triglycerides, and insulin concentrations also improved in all three groups (P< 0.05 at 6 months). Adjusting for covariates, changes in weight and fasting plasma insulin concentrations remained associated with SU changes (P< 0.05). SU reductions among those with hyperuricemia were 113, 119, and 143 mu mol/L at 6 months for low-fat, Mediterranean, and low-carbohydrate diets (allPfor within-group comparison < 0.001;P> 0.05 for between-group comparisons) and 65, 77, and 83 mu mol/L, respectively, at 24 months (allPfor within-group comparison < 0.01;P> 0.05 for between-group comparisons). CONCLUSIONS Nonpurine-focused weight loss diets may simultaneously improve SU and cardiovascular risk factors likely mediated by reducing adiposity and insulin resistance. These dietary options could provide personalized pathways to suit patient comorbidity and preferences for adherence.