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Researchers studied patients with type 2 diabetes and identified 13 metabolites that were significantly linked to a higher risk for diabetic retinopathy.
Numerous metabolites from diverse pathways are linked with an augmented and diminished risk for diabetic retinopathy (DR) in patients with T2D, according to a longitudinal study published in The Journal of Clinical Endocrinology & Metabolism.
“Recent advances in omics, especially metabolomics, offer the possibility of identifying novel potential biomarkers for DR,” wrote Lilian Fernandes Silva, PhD, and colleagues.
The authors added that multiple sample sources, the diverse application of technologies to measure metabolites, and the cross-sectional nature of previous research have complicated comparisons across studies. Furthermore, “it is challenging to compare the results from different studies of DR [because] previous studies have included only a limited number of participants.”
To bridge the gap, the researchers conducted a 12-year follow-up study, examining 1,349 participants with T2D (1,021 without DR and 328 with DR) from the METSIM study cohort. The investigators excluded 63 participants with a DR diagnosis before the original study.
The DR diagnosis was confirmed using fundus photography examination. The researchers conducted non-targeted metabolomics profiling to identify relevant metabolites.
After adjusting for confounding factors, the researchers found that 17 metabolites were meaningfully linked with the increased incidence of DR. The amino acids N-lactoyl isoleucine, N-lactoyl valine, N-lactoyl tyrosine, N-lactoyl phenylalanine, N-(2-furoyl) glycine, and 5-hydroxylysine correlated with an augmented risk for DR, and citrulline was associated with a reduced risk.
“Among the fatty acids N,N,N-trimethyl-5-aminovalerate was associated with an increased risk for DR, and myristoleate (14:1n5), palmitoleate (16:1n7), and 5-dodecenoate (12:1n7) with a decreased risk for DR. Sphingomyelin (d18:2/24:2), a sphingolipid, was significantly associated with a decreased risk for DR,” the authors wrote.
N-lactoyl-amino acids increased DR risk by 28% to 35%. In addition, patients with DR had significantly increased levels of four organic compounds: 3-hydroxypyridine sulfate, 4-vinylphenol sulfate, 4-ethylcatechol sulfate, and dimethyl sulfone. The researchers noted that these compounds have not been associated with DR in previous studies.
“Our longitudinal study shows that the development of DR involves multiple changes in metabolism that ultimately impair retina function. These changes in the retina, reflected by concentration changes in metabolites, include activation of inflammatory pathways, capillary loss, neovascularization, fibrosis, collagen degradation, endothelial dysfunction, hemorrhages, and aneurysms,” Dr. Fernandes Silva and colleagues concluded.
