| Title: | A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits |
| Journal: | Communications Biology |
| Published: | 8 Mar 2024 |
| DOI: | https://doi.org/10.1038/s42003-024-05977-1 |
| URL: | http://dx.doi.org/10.1038/s42003-024-05977-1 |
Publication 8527
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Abstract
We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.</p>
8 Authors
- Tommy H. T. Wong
- Jacky M. Y. Mo
- Mingqi Zhou
- Jie V. Zhao
- C. Mary Schooling
- Baoting He
- Shan Luo
- Shiu Lun Au Yeung
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