Title : Body Mass Index and Diabetic Nephropathy: A Mendelian Randomization Study
Abstract:
Background and objectives: The association between obesity and diabetic nephropathy (DN) has been studied but the results of these epidemiological studies are not entirely consistent. The causal effect of body mass index (BMI) on DN and kidney traits was evaluated by the individual's inborn genetic markers.
Design, setting, participants, and measurements: This was a two-sample Mendelian randomization (MR) analysis. A total of 59 independent genetic variants were selected as instrumental variables for BMI in 158,284 participants from Biobank Japan, and their effects on DN risk, eGFR and proteinuria were estimated in 3972 Chinese individuals with type 2 diabetes. Then, subgroup analysis was performed with different BMI levels or sex.
Results: We found that a one standard deviation increase in BMI was causally associated with a 3-fold increase in the risk of DN (odds ratio [OR], 4.05; 95% confidence interval [95% CI], 2.10 to 7.82; P<0.001), and a 35% decrease of eGFR level (OR, 0.65; 95% CI, 0.54 to 0.78; P<0.001). However, BMI was not associated with the level of proteinuria (OR, 1.26; 95% CI, 0.89 to 1.79; P=0.19). In addition, subgroup analysis showed a positive association between BMI and the risk of DN in individuals with different BMI levels (BMI≥25 vs BMI<25 kg/m2) or sex. Analyses stratified by sex indicated the casual effect of BMI on DN was stronger in women (OR, 9.82; 95% CI, 1.83 to 52.67; P=0.008) than in men (OR, 3.39; 95% CI, 1.23 to 9.34; P=0.02).
Conclusions: Genetic evidence showed that higher BMI levels was causally associated with increased risk of DN and decreased eGFR level, but not with proteinuria. The DN risk for women was more susceptible to BMI levels than men.
