Abstract

Background: Prior research has found a cross-sectional association between obesity and serum urate (SU) levels. However, only limited studies evaluated the effect of weight changes on SU-level changes. Objectives: This study aimed to determine if weight changes render clinically relevant changes to SU levels. We also evaluated the impact of weight reduction on achieving the target SU level (SU <6 mg/dL) in hyperuricemic participants (prior SU ≥7 mg/dL). Methods: We analyzed a systematically collected longitudinal database of annual medical examinations in Japan. We included participants who underwent the examinations at a preventive medicine center in a tertiary care hospital from October 2012 to October 2022. Participants who received pharmacological treatment for hyperuricemia or gout during the study period were excluded. The exposures of interest were categorized weight changes, increase or decrease, between two consecutive examination visits as follows: minimal (-0.9 to 0.9 kg), mild (1.0 to 4.9 kg), moderate (5.0 to 9.9 kg), and large (≥10.0 kg). The outcomes included changes in SU level between visits and achievement of the target SU level. A mixed-effect linear model with random intercepts evaluated the concurrent association between categorical weight change and SU change. We performed subgroup analyses stratified by gender, prior SU level, prior body mass index (BMI), and a previous physician diagnosis of hyperuricemia or gout. A generalized estimating equation with a logit link calculated the adjusted odds ratios (ORs) of categorial weight change for achieving target SU in hyperuricemic participants. In all analyses, we adjusted for covariates at prior visits: age, sex, BMI, eGFR, SU, history of hyperuricemia or gout, relevant medication use (medications for hypertension, diabetes, dyslipidemia, angina or myocardial infarction, and transient ischemic attack or cerebral infarction), smoking status, alcohol intake, and relevant dietary consumption (carbohydrate, meat and eggs, seafood, soy products, milk and dairy product, vegetables, fruits, sweets, and fatty diet). Change variables between two visits, including dietary changes, changes in smoking status, alcohol intake changes, eGFR changes, and changes in relevant medication, were also included in the model. Results: A total of 63,493 participants with 370,591 visits and 347,257 person-years follow-ups were analyzed. The median age was 47 years, 55.0% were female, the median BMI was 21.8 m/kg2 (IQR: 19.8, 24.1), and the median follow-up was 5.5 years (IQR: 2.7-8.7). Compared to those with minimal weight changes (-0.9 to 0.9 kg), the adjusted mean changes in SU levels were -0.09 (95% confidence interval [CI]: -0.10, -0.09) mg/dL in mild weight reduction (-1.0 to -4.9 kg), -0.32 (95%CI: -0.34, -0.31) mg/dL in moderate weight reduction (-5.0 to -9.9 kg), and -0.60 (95%CI: -0.64, -0.56) mg/dL in large weight reduction (-10.0 kg or more). The associations of weight reduction with SU were consistent in subgroups and tended to be larger in patients with hyperuricemia and overweight or obese patients (Figure 1). In hyperuricemic participants (median SU 7.5 [IQR:7.2, 7.9] mg/dL), adjusted OR (95%CI) for achieving target SU were 1.36 (1.22, 1.51) in mild weight reduction (-4.9 to -1.0 kg), 3.71 (3.08, 4.49) in moderate weight reduction (-9.9 to -5.0 kg), and 9.37 (6.67, 13.15) in large weight reduction (-10.0 kg or more). The corresponding numbers needed to treat (95%CI) were 55.6 (38.5, 90.9) for mild, 8.0 (6.5, 10.2) for moderate, and 3.3 (2.6, 4.4) for large weight reduction (Table 1). Conclusion: This large longitudinal study found a robust association between weight change and SU level changes. Mild weight changes were associated with limited changes in SU levels. In a given patient, moderate to large weight reductions were required for clinically relevant SU improvement, achieving the target SU level. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Sho Fukui: None declared, Masato Okada: None declared, Tomohiro Shinozaki: None declared, Takehiro Nakai: None declared, Hiroki Ozawa: None declared, Hiromichi Tamaki ABBVIE, Ayumi pharma、Astellas、Astrazeneca 、Asahi Kasei pharma, Eli Lily、Eisai、Ono Pharmaceutical、Otsuka pharma、Dai-Ichi Sankyo、Chugai、Tanabe-Mitsubishi、GSK, and Pfizer, Mitsumasa Kishimoto: None declared, Javier Marrugo: None declared, Sara K. Tedeschi SKT reports consulting fees from Novartis., Hyon Choi HKC reports serving on the ANI Pharmaceuticals, Inc, advisory board and the LG Chem Ltd steering committee, HKC reports receiving grant funding from Horizon Therapeutics, Daniel H. Solomon DHS reports salary support through research contracts to his institution from CorEvitas, Janssen, and Novartis.