Insulin resistance as a potential mediator between central obesity and diabetic kidney disease risk in type 2 diabetes

Abstract

Abstract Obesity is a key risk factor for diabetic kidney disease (DKD). However, BMI fails to capture body fat distribution. We hypothesized that central obesity, rather than generalized obesity, is associated with DKD risk in patients with type 2 diabetes mellitus (T2DM), and that this association is mediated by insulin resistance (IR). A cross-sectional study of 4674 community-managed T2DM patients in Kaihua County, Zhejiang Province. Participants were classified into four obesity phenotypes based on BMI and waist circumference (WC). DKD was defined as UACR ≥ 30 mg/g and/or eGFR < 60 mL/min/1.73 m 2 . Multivariable logistic regression and mediation analysis were used to assess the associations and the mediating role of HOMA-IR. The overall prevalence of DKD in the study population was 52.439%, and the overall prevalence of obesity was 42.790%, with central obesity being predominant. DKD prevalence was significantly higher in the IR group compared to the non-IR group (60.046% vs. 48.001%, P < 0.001). Multivariable logistic regression showed that after adjustment for demographic and lifestyle factors, isolated central obesity (OR 1.214, 95% CI 1.053–1.399, P = 0.007) and combined generalized and central obesity (OR 1.189, 95% CI 1.001–1.412, P = 0.048) were significantly associated with DKD risk, while isolated generalized obesity showed no significant association ( P > 0.05). After further adjustment for metabolic factors including glycemic parameters, IR, and lipid profiles, these associations were attenuated and no longer statistically significant ( P > 0.05). Mediation analysis revealed that in the basic model, HOMA-IR explained 22.484% of the association between central obesity and DKD (indirect effect P < 0.001). After adjusting for BMI and multiple covariates, this explanatory proportion remained 9.715% ( P = 0.006). Central obesity is associated with DKD risk in community-managed T2DM patients, and this association was attenuated after metabolic adjustment. These findings suggest that metabolic disturbances including IR may contribute to the central obesity–DKD link. WC measurement could be considered alongside BMI for DKD risk stratification.