Cross-ethnic Molecular Signatures Underpin the Adverse Impact of Statin Use on Type 2 Diabetes
The use of statins as the primary therapy for reducing low-density lipoprotein cholesterol has raised concerns regarding their potential side effects in increasing the risk of type 2 diabetes (T2D). However, the underlying mechanism remains largely unknown. In this study, we utilized multi-omics molecular signatures to unravel the etiology of statin-induced T2D. Through systematic screening of 102 gut microbial features, 40 blood metabolites, and 131 circulating proteins in East Asians and Europeans, we identified a set of blood metabolites and proteins potentially influenced by genetically proxied statin use. Notably, Mendelian randomization analyses provided evidence that elevated circulating levels of gastric inhibitory polypeptide (GIP) were associated with an increased risk of T2D. This association between genetically proxied statin use and GIP was consistently observed across East Asian and European populations, highlighting the pivotal role of GIP in modulating the risks of statin-induced T2D. Furthermore, this study established an extensive atlas of multi-omics molecular signatures associated with statin-induced T2D, offering valuable insights for prioritizing intervention targets.
Authors
- Tiannan Guo (ORCID: https://orcid.org/0000-0003-3869-7651)
- Zhangzhi Xue (ORCID: https://orcid.org/0000-0001-7311-6221)
- Wei Hu (ORCID: https://orcid.org/0000-0001-9332-9670)
- Luqi Shen (ORCID: https://orcid.org/0009-0003-4349-4063)
- Yuanqing Fu (ORCID: https://orcid.org/0000-0002-3955-9376)
- Xue Cai (ORCID: https://orcid.org/0000-0002-7427-2100)
- Menglei Shuai (ORCID: https://orcid.org/0000-0001-9983-1477)
- Bangyan Li (ORCID: https://orcid.org/0000-0001-7446-2505)
- Shuai Yuan (ORCID: https://orcid.org/0000-0001-5055-5627)
- Ju‐Sheng Zheng (ORCID: https://orcid.org/0000-0001-6560-4890)
- Fengzhe Xu (ORCID: https://orcid.org/0000-0002-2686-1445)
- Yu‐Ming Chen (ORCID: https://orcid.org/0000-0003-1658-5528)
- Liang Yue (ORCID: https://orcid.org/0000-0001-6478-7306)
- Wanglong Gou (ORCID: https://orcid.org/0000-0002-4256-9452)
- Min Yang (ORCID: https://orcid.org/0009-0000-5429-9253)
- Zelei Miao (ORCID: https://orcid.org/0000-0001-9478-1933)
Institutions
- Sun Yat-sen University (CN)
- Karolinska Institutet (SE)
- Westlake University (CN)
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
Publication Details
- Journal
- Genomics Proteomics & Bioinformatics
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1093/gpbjnl/qzaf101
- Citations
- 1
- Primary Topic
- Lipoproteins and Cardiovascular Health
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- Westlake University
- National Natural Science Foundation of China
- Sun Yat-sen University
- Recruitment Program of Global Experts
- Zhejiang Provincial Ten Thousand Plan for Young Top Talents