Blood metabolome of cardiovascular disease, diabetic kidney disease, and diabetic retinopathy in type 2 diabetes patients: A systematic review and meta-analysis
Abstract
Methods: MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library were searched for relevant articles published before August 1, 2023. Studies assessing the association between circulating metabolites and CVD, including coronary heart disease, strokes, heart failure, CV death, DKD, and DR in T2D were eligible for review. We performed meta-analyses for metabolites with ≥2 estimates and reported adjusted odds ratios (ORs) of outcome per SD increase of metabolite. I2 tests were used to assess the study heterogeneity.
Results: We identified 74 total studies (n = 48 cross-sectional and n = 26 cohort; 33 exclusively for CVD, 21 exclusively for DKD, and 20 exclusively for DR, 19 for more than one outcome; a total of 49,866 T2D patients, mean age 60 years, 55% male) describing metabolism of Trimethylamine N-oxide (TMAO), amino acids, fatty acids, sugars, sphingolipids, phospholipids, organic compounds, bacteria, and enzymes. Eleven metabolites were included in meta-analyses for their association with CVD. These include TMAO (OR 1.1, 95% confidence interval (CI) 0.91-1.3) and derivatives (choline: 0.95, 0.76-1.18, carnitine: 1.08, 0.86-1.36, betaine: 1.00, 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, 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 >30%.
Conclusions: In…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 49,866 participants or records.
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