Novel Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Three Asian Cohorts

Abstract

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004–11) representing three major Asian ethnic groups (aged 40–80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.

Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective

“…Glutamine and arginine tend to increase in peripheral blood samples from DR, AMD, and ROP patients according to the analysis of metabolomics [17][18][19][20][21]23,[25][26][27][28][29]43,45,52,55,56,58], which makes it possible and reasonable for glutamine and arginine to be the biomarkers used in early diagnosis of retinopathy. In addition, the level of alanine rises in DR patients in intraocular fluids, blood samples, and even in CSF and urine while not showing clear tendency in AMD and ROP [19,22,27,[31][32][33]. This distinction between diseases leads to the possibility of alanine being the specific biomarker for DR.…”

Formate Might Be a Novel Potential Serum Metabolic Biomarker for Type 2 Diabetic Peripheral Neuropathy

“…Metabolomic analysis, as a rapidly emerging technology, has developed into an important means for the identification of metabolites from biochemical pathways that are changed on account of disease or therapeutic intervention. There were some studies involving metabolomics in diabetes, 13 , 28 , 29 but the characteristics of serum metabolites in DPN were rarely explored. Reviewing the literatures, we were the first to explore the serum metabolites of DPN via 1 H-NMR metabolomics technology.…”

Prediction of diabetic kidney disease risk using machine learning models: A population-based cohort study of Asian adults

“…The 14 lipoprotein subclasses include six subclasses of VLDL (extremely large, very large, large, medium, small, very small), IDL, three subclasses of LDL (large, medium, small), and four subclasses of HDL (very large, large, medium, small). Lipid concentration within each lipoprotein particle included triacylglycerol, total cholesterol, non-esterified cholesterol and cholesteryl ester levels, and phospholipid concentrations ( Quek et al, 2021 ). Of the 228 metabolites, pyruvate, glycerol, and glycine were not available in Malays.…”