Causal relationship between obesity and diabetic neuropathy: A 2-sample Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Metabolic Disorders
• Neurology

Background:

• Obesity is increasingly linked to diabetic neuropathy (DN), but causal evidence is lacking.
• Understanding the causal relationship is crucial for developing effective prevention and treatment strategies for DN.
• Mendelian randomization (MR) offers a robust approach to infer causality from observational data.

Purpose of the Study:

• To investigate the potential causal relationship between obesity indicators and diabetic neuropathy (DN).
• To assess whether body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) causally influence DN risk.

Main Methods:

• A Mendelian randomization (MR) analysis was performed using genetic variants associated with DN.
• Summary statistics from genome-wide association studies (GWAS) for obesity measures (BMI, WC, HC, WHR) were utilized.
• Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were employed for causal effect estimation, with sensitivity analyses conducted.

Main Results:

• Inverse-variance weighted analysis indicated a significant negative association between BMI, WC, and HC with DN risk.
• After Bonferroni correction, a statistically significant causal relationship was found between BMI and DN.
• No significant causal relationships were observed for WC, HC, or WHR with DN, with BMI showing a potential slight protective effect.

Conclusions:

• Body mass index (BMI) may exert a protective effect against the risk of developing diabetic neuropathy (DN).
• The study provides genetic evidence supporting a causal link between BMI and DN.
• Further research is warranted to elucidate the complex interplay between obesity metrics and DN pathogenesis.