6720 Metabolomics And Risk Of Vascular Complications In Type 2 Diabetes - A Systematic Review and Meta-Analysis
Authors: Yoshida Yilin , Kuo Sydney , Li Danting , Corder Amy , Wargny Matthieu , Yoshida Tadashi 
Published: October 2024

Disclosure: Y. Yoshida: None. S. Kuo: None. D. Li: None. A. Corder: None. M. Wargny: None. T. Yoshida: None.

Aim: To systematically evaluate metabolite markers for micro- and macrovascular complications in patients with type 2 diabetes (T2D) in studies using high-throughput methods. Methods: We searched MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library and hand-searched reference lists of relevant articles published before August 1, 2023. We included studies assessing the association between circulating metabolites and cardiovascular disease (CVD), including coronary heart disease, stroke, heart failure, CV death, diabetic kidney disease (DKD), and diabetic retinopathy (DR) in T2D. We performed meta-analyses for metabolites with ≥ 2 estimates and reported adjusted odds ratios (ORs) of outcome per SD of metabolite. We used I2 tests to assess study heterogeneity. Results: We identified 74 total studies (48 cross-sectional and 26 cohorts; 33 for CVD, 21 for DKD, and 20 for DR, 19 with 1+ outcomes; a total of 47,267 T2D patients with mean age 60 years) covering metabolisms of amino acids, trimethylamine N-oxide (TMAO), fatty acids, sugar/energy, fluid balance, sphingolipids, phospholipids, organic acids, bacteria, and enzymes. Eleven total metabolites had &gt;2 estimates for their associations with CVD and were included in meta-analyses, including TMAO (OR 1.1, 95% CI 0.91-1.3) and TMAO derivatives (choline: 0.95, 0.76-1.18, carnitine: 1.08, 0.86-1.36, betaine: 1.0, 0.91-1.11), branched-chain amino acids (leucine:1.12, 0.05-25.5, valine:1.14, 0.09-14.2, isoleucine: 1.02, 0.76-1.35), other amino acids (glutamine:1.02, 0.35-2.9, alanine: 0.99, 95% CI 0.87-1.13), and metabolites for energy metabolism (lactate: 1.11, 0.81-1.52, glycerol: 1.05, 0.61-1.81). I2 for all studies &gt;30%. Metabolites with one estimate from cohort studies and two common estimates from cross-sectional studies that were associated with vascular outcomes were narratively summarized. Among amino acids, histidine and tyrosine were associated with a lower CVD risk. Isoleucine, norvaline, and valine were associated with a higher DKD risk. Arginine, citrulline, and ornithine were associated with a higher risk, and glutamate, lysine, and tryptophan with a lower risk for DR. TMAO derivates, carnitine and choline were associated with a higher risk of DKD and DR. DHA was associated with a lower CVD risk. Phosphatidylcholine diacyl C38:0 was associated with a higher risk of DKD. 1,5-anhydroglucitol was associated with a reduced risk of DKD. Conclusions: TMAO and amino acids are the most studied circulating metabolites for diabetic complications in our review. TMAO was marginally associated with the risk of CVD. However, the findings are inconclusive and derived from heterogeneous studies. Our review suggested insufficient evidence of circulating metabolites in predicting vascular complications in T2D, and large prospective studies are needed to substantiate the evidence in this area.

Presentation: 6/3/2024