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)

Objectives: <a>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. </a>We aim to examine the effects of weight loss diets on SU and cardiometabolic risk factors. <p>Research Design and Methods: Secondary study of the Dietary Intervention Randomized Controlled Trial (DIRECT) using 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 (SU³416 μmol/L), a relevant subgroup at risk for gout.</p> <p>Results: Among all participants, average SU decreases were 48 μmol/L at 6-months and 18 μmol/L at 24-months, with no differences between diets (p>0.05). Body weight, HDL-C, total cholesterol to 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 μmol/L at 6 months for low-fat, Mediterranean, and low-carbohydrate diets (all p for within-group comparison <0.001; p>0.05 for between-group comparisons), and 65, 77, and 83 μmol/L, respectively, at 24-months (all p for within-group comparison <0.01; p>0.05 for between-group comparisons).</p> <a>Conclusions</a>: <a>Non-purine-focused weight loss diets may simultaneously improve SU and cardiovascular risk factors, likely mediated by reducing adiposity and insulin resistance. </a>These dietary options could provide personalized pathways to suit patient comorbidity and preferences for adherence.