Original Abstract

OBJECTIVE: Body weight variability is linked to cardiometabolic outcomes, but its renal impact in type 2 diabetes remains uncertain. We tested whether the magnitude of seasonal BMI fluctuation is independently associated with kidney function decline. RESEARCH DESIGN AND METHODS: We analyzed a nationwide, multicenter Japanese cohort (2014-2020). Monthly BMI was modeled using seasonal-trend locally estimated scatterplot smoothing to quantify each participant's within-year peak-to-trough difference. The primary outcome was ≥40% decline in estimated glomerular filtration rate (eGFR). Secondary outcomes were ≥30% eGFR decline, creatinine doubling, incident chronic kidney disease (CKD) stage ≥3, and kidney failure. Associations were estimated using multivariable Cox models with clinic as a random effect. RESULTS: Among 6,700 outpatients (median follow-up: 6.8 years), 779 reached the primary end point. Each 1-SD increase in BMI fluctuation was associated with higher risk of ≥40% eGFR decline (hazard ratio [HR] 1.23, 95% CI 1.16-1.31). The highest versus lowest tertile showed a 1.7-fold increased risk (HR 1.72, 95% CI 1.42-2.09). Patterns were consistent for ≥30% eGFR decline (HR 1.18, 95% CI 1.13-1.23), creatinine doubling (HR 1.30, 95% CI 1.17-1.45), and incident CKD stage ≥3 (HR 1.11, 95% CI 1.07-1.16). Longitudinal analyses showed steeper eGFR decline in the highest-fluctuation group. Results were robust across sensitivity analyses, including models for time-varying medication exposure. CONCLUSIONS: In type 2 diabetes, larger intra-annual BMI fluctuations were independently and dose-dependently associated with kidney function decline. Seasonal BMI amplitude may identify higher-risk individuals; whether reducing seasonal BMI fluctuations improves kidney outcomes warrants prospective evaluation.