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- Title
Effect of Metabolite Levels on Type 2 Diabetes Mellitus and Glycemic Traits: A Mendelian Randomization Study.
- Authors
Yue Sun; Ya-Ke Lu; Hao-Yu Gao; Yu-Xiang Yan; Sun, Yue; Lu, Ya-Ke; Gao, Hao-Yu; Yan, Yu-Xiang
- Abstract
<bold>Objective: </bold>To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits.<bold>Methods: </bold>Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P < 5 × 10-8) were selected from public genome-wide association studies, and single-nucleotide polymorphisms of outcomes were obtained from the Diabetes Genetics Replication and Meta-analysis consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related Traits Consortium for fasting glucose, insulin, and glycated hemoglobin (HbA1c). The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis.<bold>Results: </bold>The β estimates per 1-SD increase of arachidonic acid (AA) level was 0.16 (95% CI, 0.078-0.242; P < 0.001). Genetic predisposition to higher plasma AA levels were associated with higher fasting glucose levels (β 0.10 [95% CI, 0.064-0.134], P < 0.001), higher HbA1c levels (β 0.04 [95% CI, 0.027-0.061]), and lower fasting insulin levels (β -0.025 [95% CI, -0.047 to -0.002], P = 0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have a positive causal effect on glycemic traits.<bold>Conclusions: </bold>Our findings suggest that AA and 2-HBA may have causal associations on T2DM and glycemic traits. This is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.
- Subjects
CHINA; METABOLITES; TYPE 2 diabetes; SINGLE nucleotide polymorphisms; BLOOD sugar analysis; RESEARCH; SEQUENCE analysis; RESEARCH methodology; METABOLISM; GENETIC polymorphisms; PROGNOSIS; MEDICAL cooperation; EVALUATION research; INSULIN; COMPARATIVE studies; DISEASE susceptibility; RESEARCH funding; PHENOTYPES
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 12, p3439
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab581