Higher body mass index (BMI) has been linked to an increased risk for diabetic nephropathy, new research finds.
The study of nearly 4000 East Asian individuals with type 2 diabetes used genetic analysis to show that higher BMI was associated with both an increased risk for diabetic nephropathy and decreased estimated glomerular filtration rate (eGFR), particularly in women.
The findings were published online February 22 in the Journal of Clinical Endocrinology and Metabolism by Jingru Lu, PhD, of the National Clinical Research Center of Kidney Diseases, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China, and colleagues. “These results provide a theoretical basis for the potential therapeutic benefits of reducing BMI to prevent the occurrence and progression of diabetic nephropathy,” the authors write.
“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,” author Zhi-Hong Liu, MD, said in a statement.
“BMI is established as a causal risk factor for diabetic kidney disease, and in fact, appears to be a causal risk factor for any chronic kidney disease. The [new] study helps show the results from other populations linking obesity to kidney disease risk extends to Asian populations,” William G. Herrington, MD, a Medical Research Council-Kidney Research David Kerr clinical scientist, Oxford, UK, told Medscape Medical News.
Herrington was the second author on a study using data from the UK Biobank, in which both central (waist-to-hip ratio) and general adiposity (BMI) appeared to be independent and moderate causal risk factors for chronic kidney disease. In that analysis, diabetes, blood pressure, and their correlates accounted for most adiposity-CKD associations.
“This is good news because we already know a lot about diabetes and high blood pressure, and we have treatments for them. If we can prevent diabetes and control blood pressure in those who are overweight or obese, we may be able to prevent many cases of kidney disease from developing in the first place. Ultimately, these results also give us all more incentive to manage our weight,” Herrington said.
Study Used Genetic Markers for Obesity
Lu and colleagues used BMI-associated single nucleotide polymorphisms (SNPs) as genetic markers to investigate the causal role of BMI in diabetic nephropathy and kidney traits in 3972 individuals with type 2 diabetes. Genetic markers were used to control for residual confounding and reverse causality.
Each standard deviation increase in BMI was causally associated with a significant increase in diabetic nephropathy (odds ratio [OR], 3.76; P < .001) and decrease in eGFR (OR, 0.71; P < .001). The causal association of BMI with diabetic nephropathy was greater in women (OR, 14.81; P = .002) than in men (OR, 3.48; P = .02). The effect remained after removal of eight SNPs associated with potential confounders.
Variations in sex hormone levels may influence sex differences in the obesity-diabetic nephropathy association, the authors speculate. Furthermore, they say, “sex differences in fat distribution may also affect the association between obesity and diabetic nephropathy. Women have a higher body fat percentage than men at an equivalent BMI. The fat deposit in the kidney impacts renal hemodynamics and intrarenal regulation.”
No causal effect was found for BMI on the level of proteinuria (OR, 1.26; P = .22). Lu and colleagues note that although proteinuria has been considered the hallmark of diabetic kidney disease, about 40% of patients with type 2 diabetes have renal function loss without proteinuria. Obesity has also been associated with reduced renal function in the absence of proteinuria.
“Therefore, the association between BMI and proteinuria does not affect the causal effect of BMI on diabetic nephropathy or eGFR. For our nonsignificant results of BMI and proteinuria obtained from genomic data, we speculate that high BMI levels may not directly cause proteinuria which is a concomitant symptom of diabetic nephropathy, but rather BMI affects the level of proteinuria by diabetic nephropathy or other risk factors,” they write.
The study was supported by the National Rey R&D Program of China and Key R&D Projects of Jiangsu Province. The authors have reported no relevant financial relationships.
J Clin Endocrinol Metab. Published online February 22, 2022. Abstract
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.
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