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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)

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posted on 02.09.2020 by Chio Yokose, Natalie McCormick, Sharan K. Rai, Na Lu, Gary Curhan, Dan Schwarzfuchs, Iris Shai, Hyon K. Choi
Objectives: 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 aim to examine the effects of weight loss diets on SU and cardiometabolic risk factors.

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.

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).

Conclusions: Non-purine-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.

Funding

This study was supported by the National Institutes of Health [P50 AR060772 and R01 AR065944]. CY is supported by the National Institutes of Health Ruth L. Kirschstein Institutional National Research Service Award [T32 AR007258]. NM is supported by a Fellowship Award from the Canadian Institutes of Health Research. SR is supported by a Doctoral Foreign Study Award from the Canadian Institutes of Health Research. GC is supported by the National Institutes of Health [K24 DK091417].IS is supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) SFB 1052 and the Israeli Science Foundation and Israel Ministry of Science and Technology.

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