Insulin resistance mediates associations of weight gain with serum uric acid and hyperuricemia in Chinese population.

BACKGROUND: Studies on the association between weight change and serum uric acid (SUA) or hyperuricemia (HUA) remain limited, and the underlying mechanisms remain unclear. OBJECTIVE: This study aimed to explore the relationships between weight change and SUA or HUA among Chinese adults, and to assess the mediating role of insulin resistance (IR). METHODS: We analyzed data from participants who underwent at least two annual health examinations between January 2015 and May 2025. Weight change (%) was calculated as (follow-up value - baseline value)/baseline value. Generalized linear models and logistic regression were used to examine the associations of weight change with SUA and HUA, while mediation analysis was applied to evaluate the mediating effects of IR indices. RESULTS: A total of 16,688 eligible participants was included, with 15.0% having HUA. The median follow-up duration was 2.00 (1.00, 4.00) years. Each 1-standard deviation (SD) increase in weight change was associated with a 10.48 μmol/L increase in SUA, and a 30.0% higher risk of HUA. Atherogenic index of plasma (AIP), triglyceride-glucose index (TyG), triglyceride-glucose body mass index (TyG-BMI), and the metabolic score for insulin resistance (METS-IR) were positively linearly associated with SUA and HUA. All four IR indices partially mediated the associations of weight change with SUA levels and HUA risk. Compared with individuals with stable weight, the weight loss group was associated with a significantly lower HUA risk, while the weight gain group had a 78% higher HUA risk. CONCLUSIONS: Weight gain was associated with the elevated SUA levels and increased HUA risk, and insulin resistance may be one of the underlying mechanisms.