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February 22, 2022
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Obesity may increase diabetic kidney disease risk, especially in women

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Adults with type 2 diabetes and a higher BMI may have an increased risk for diabetic kidney disease, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.

In findings from a generalized summary Mendelian randomization using 56 BMI-associated single nucleotide polymorphisms instrument variables, increasing BMI was linked to an increased risk for diabetic nephropathy and a lower estimated glomerular filtration rate, with the effects most pronounced among women.

Risk for diabetic nephropathy with type 2 diabetes increases with BMI
The risk for diabetic nephropathy rises with each 1 kg/m2 increase in BMI, with women having a more pronounced increased risk than men. Data were derived from Lu J, et al. J Clin Endocrinol Metab. 2022;doi:10.1210/clinem/dgac057.

“Our research highlights how obesity contributes to the incidence and progression of diabetic nephropathy in people with type 2 diabetes, especially for women,” Zhihong Liu, MD, director of the National Clinical Research Center of Kidney Disease at Jinling Hospital and Nanjing University School of Medicine in Nanjing, China, said in a press release. “Managing your blood pressure and blood sugar may not be enough to slow the progression to end-stage renal disease, and our study shows how important it is for people with diabetes to also manage their weight.”

Researchers conducted a Mendelian randomization analysis to evaluate the causal effect of BMI on diabetes nephropathy risk and kidney traits. Fifty-six BMI-associated genetic variants from the BioBank Japan GWAS Mendelian randomization analyses to serve as instrumental variables. The study cohort included 1,347 adults with type 2 diabetes and biopsy-proven diabetic nephropathy, and 2,716 adults with diabetes for more than 10 years and no kidney disease. Mendelian randomization was conducted with all participants to analyze the causal effect on BMI on diabetic nephropathy, eGFR and proteinuria. Subgroup analysis stratifying participants by sex was also conducted using 27 genetic variants associated with BMI in men and 16 variants associated with BMI in women.

In the Mendelian randomization analysis, each 1 kg/m2 increase in BMI was associated with a higher risk for diabetic nephropathy (OR = 3.76; 95% CI, 1.88-7.53; P < .001) and lower levels of eGFR (OR = 0.71; 95% CI, 0.59-0.86; P < .001). There was no association between BMI and proteinuria level.

In subgroup analyses, each 1 kg/m2 increase in BMI increased the risk for diabetic nephropathy for men and women. However, the increased risk was much higher among women (OR = 14.81; 95% CI, 2.67-82.05; P = .002) than men (OR = 3.48; 95% CI, 1.18-10.27; P = .02).

“The increase in BMI level had a more significant influence on the risk of diabetic nephropathy in women,” the researchers wrote. “These results provide a theoretical basis for the potential therapeutic benefits of reducing BMI to prevent the occurrence and progression of diabetic nephropathy.”

Liu said the findings confirm the importance of screening for kidney complications for adults with diabetes and obesity.

“People with diabetes and obesity should have their kidneys checked more often, as they are at high risk, and while chronic kidney disease has no cure, early detection and obesity treatment could slow the progression to end-stage kidney disease,” Liu said in a press release.