医学
内科学
糖尿病
亚临床感染
体质指数
冠状动脉疾病
代谢组学
代谢物
内分泌学
2型糖尿病
生物信息学
生物
作者
Parag A Chevli,Barry I. Freedman,Fang‐Chi Hsu,Jianzhao Xu,Megan E. Rudock,Lijun Ma,John S. Parks,Nicholette D. Palmer,Michael D. Shapiro
标识
DOI:10.1186/s12933-021-01419-y
摘要
Abstract Background Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). Methods The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. Results At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. Conclusions Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.
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