ArticleJournal of diabetes investigation2025
Causal relationship between body mass index and insulin resistance: Linear and nonlinear Mendelian randomization study in a Japanese population.
Article in Journal of diabetes investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Changes in Insulin Resistance with Different Weight Loss Methods in Patients with Type Two Diabetes Mellitus and Hypertension: A Comparative Clinical Trial.Journal of clinical medicine · 2026Article
- Association between the triglyceride-glucose index and risk of type 2 diabetes mellitus and the mediating effect of BMI: a comparative analysis in Chinese and Japanese populations.Frontiers in endocrinology · 2026Article
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Authors and funding
20 authors.
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Abstract
AIMS/
introductionObesity is a known risk factor for several chronic diseases, including type 2 diabetes mellitus, which results from increased insulin resistance and impaired insulin secretion. However, the association between obesity and insulin resistance in Asian populations has not yet been fully elucidated. Therefore, we aimed to investigate the causal relationship between body mass index (BMI) and glycemic traits using Mendelian randomization (MR). MATERIALS AND
methodsWe performed individual-level MR analyses using genetic risk scores based on BMI-related variants in 3,745 individuals without diabetes mellitus from a Japanese cohort. We examined heterogeneity through subgroup analyses based on potential modifiers and determined the shape of the causal relationship using nonlinear MR analyses to further assess the impact of BMI on the homeostasis model assessment of insulin resistance (HOMA-IR).
resultsMR analyses revealed a significant positive association between BMI and HOMA-IR (β = 0.077; 95% confidence interval, 0.014-0.141; P = 0.016; outcome variable was log-transformed and standardized). Additional analyses revealed heterogeneity among subgroups differentiated by age, sex, lifestyle habits, and cardiometabolic traits. Nonlinear MR analyses suggested a potential J-shaped causal relationship between BMI and HOMA-IR.
conclusionsOur findings demonstrated that obesity and low BMI may contribute to increased insulin resistance. Furthermore, the impact of BMI on insulin resistance could vary owing to effect modification. Managing BMI is crucial in individuals at high risk of increased insulin resistance and may have important implications for preventing type 2 diabetes, especially given the low insulin secretory capacity observed in East Asian populations.
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