China: Study Links Higher BMI in Adults with Type 2 Diabetes to Increased Risk of Diabetic Nephropathy

Higher BMI in adults with type 2 diabetes is associated with an increased risk of diabetic nephropathy (DN) and decreased estimated glomerular filtration rate (eGFR) levels. The effects were more pronounced in women, reveals a recent study. The study appears in the Journal of Clinical Endocrinology & Metabolism.

Zhihong Liu, Nanjing University School of Medicine, Nanjing, China, and colleagues undertook a study with an objective to explore the causal effect of body mass index (BMI) on DN, eGFR, and proteinuria in type 2 diabetes by a two-sample Mendelian randomization analysis. The study was necessary keeping in mind the inconsistency of the associations of obesity and DN in type 2 diabetes in observational studies and ambiguity of the causality.

For this purpose, the researchers selected a total of 56 genetic variants as instrumental variables for BMI in 158,284 participants from BioBank Japan. Their effects on DN risk, eGFR, and proteinuria were estimated in 3972 individuals having type 2 diabetes. Sex-stratified MR analysis was performed between BMI and DN. Generalized summary Mendelian randomization (GSMR) analysis was selected as the primary method.

Study Findings

• One standard deviation increase in BMI was causally associated with higher DN risk (OR, 3.76), and lower eGFR level (OR, 0.71).
• BMI was not causally associated with proteinuria.
• Sex-stratified analyses indicated the causal effect of BMI on DN was stronger in women (OR, 14.81) than in men (OR, 3.48).
• Sensitivity analyses did not show evidence for violation of the MR assumptions.

"Genetic evidence demonstrated that higher BMI levels were causally associated with increased risk of DN and decreased eGFR levels," wrote the authors. "Moreover, the escalation in BMI level had a greater impact on DN risk in women."

"These results provide a theoretical basis for the potential therapeutic benefits of reducing BMI to prevent the occurrence and progression of diabetic nephropathy."

"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.

Reference

Jingru Lu, PhD, Xiaoshuang Liu, MSc, Song Jiang, PhD, Shuyan Kan, PhD, Yu An, PhD, Chunxia Zheng, PhD, Xiang Li, PhD, Zhihong Liu, MD, Guotong Xie, PhD, Body Mass Index and Risk of Diabetic Nephropathy: A Mendelian Randomization Study, The Journal of Clinical Endocrinology & Metabolism, 2022;, dgac057, https://doi.org/10.1210/clinem/dgac057