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Body Mass Index and Risk of Diabetic Nephropathy: A Mendelian Randomization Study
Jingru Lu1,2, Xiaoshuang Liu3, Song Jiang2
1School of Medicine, Southeast University, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, China.
The Journal of Clinical Endocrinology and Metabolism
|February 22, 2022
Summary
Higher body mass index (BMI) causally increases diabetic nephropathy (DN) risk and lowers kidney function in type 2 diabetes. This effect is significantly stronger in women, highlighting sex-specific impacts of obesity on kidney health.
Area of Science:
- Genetics
- Metabolic Disorders
- Nephrology
Background:
- Observational studies show inconsistent associations between obesity and diabetic nephropathy (DN) in type 2 diabetes, leaving causality unclear.
- Understanding the causal link between body mass index (BMI) and kidney outcomes in type 2 diabetes is crucial for effective management.
Purpose of the Study:
- To investigate the causal effect of body mass index (BMI) on diabetic nephropathy (DN), estimated glomerular filtration rate (eGFR), and proteinuria in individuals with type 2 diabetes.
- To explore potential sex differences in the causal relationship between BMI and DN.
Main Methods:
- Utilized a 2-sample Mendelian randomization (MR) analysis with 56 genetic variants for BMI as instrumental variables.
- Analyzed data from BioBank Japan (158,284 participants for BMI variants) and a type 2 diabetes cohort (3,972 individuals for outcome data).
- Employed generalized summary MR analysis and six other robust methods, including sex-stratified analyses, to assess causality and test assumptions.
Main Results:
- A one standard deviation increase in BMI was causally linked to a 3.76-fold higher risk of DN and a decrease in eGFR (OR 0.71).
- No significant causal association was found between BMI and proteinuria (P=0.22).
- Sex-stratified analysis revealed a stronger causal effect of BMI on DN risk in women (OR 14.81) compared to men (OR 3.48).
Conclusions:
- Higher BMI levels are causally associated with an increased risk of DN and reduced eGFR in type 2 diabetes.
- The impact of increased BMI on DN risk is more pronounced in women.
- Findings support the role of weight management in preventing DN progression, with particular attention to women.
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