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Charumathi Sabanayagam, Rehena Sultana, Riswana Banu, Zhou Lei, Gavin SW Tan, E Shyong Tai, Ching-Yu Cheng, Tien Yin Wong; Serum and urinary metabolites associated with diabetic retinopathy in two Asian cohorts. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1897.
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Serum metabolites have been shown to be associated with diabetes and its complications including diabetic retinopathy (DR). Metabolites in urine have recently been shown to provide information independent of serum metabolites. We examined the cross-sectional association of DR with a combination of serum and urinary metabolites in two Asian cohorts.
Serum (n=225) and urinary metabolites (n=33) were quantified using nuclear magnetic resonance (NMR) spectroscopy in 1869 adults with diabetes who participated in the baseline visits (2007-2011, aged ≥40 years) of two independent population-based cohort studies (Chinese, n=581; Indians, n=1288) with similar methodology in Singapore. Diabetes-specific moderate DR was assessed from retinal photographs and defined as a level>43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Multivariate logistic regression models were constructed for each metabolite (per SD increase) adjusted for age, sex, systolic blood pressure, duration of diabetes and HbA1c. Metabolites with the same direction of association in both cohorts were selected and those achieving significance corrected for multiple testing from both cohorts were meta-analysed.
Prevalence of moderate DR was 11.2% in Chinese and 10.6% in Indians. Logistic regression identified 21 serum and 10 urinary metabolites associated with DR in one or both studies after Bonferroni correction, of which 6 serum (p<0.002) and 6 urine metabolites (p=0.005) were statistically significant in the meta-analysis. Among serum metabolites, higher levels of creatinine, total cholesterol and cholesterol esters in chylomicrons in extremely large VLDL (lipoprotein subclasses) were positively associated (odds ratios [ORs], 1.25, 1.11, 1.11) while higher levels of tyrosine, fatty acid saturation % and cholesterol esters in LDL, were inversely associated with DR (ORs 0.57, 0.60, 0.63) (Figure 1). Among urinary metabolites, higher levels of alanine, valine (aminoacids), formate (microbial), citrate (glycolysis), 3-hydroxyisovalerate, 3-hydroxy isobutyrate were inversely associated with DR with ORs ranging from 0.52 to 0.68 (Figure 2).
Our results demonstrated that adults with DR had altered serum and urinary profiles mostly confined to aminoacids, lipoprotein, glycolysis, fluid and fatty acid metabolism.
This is a 2020 ARVO Annual Meeting abstract.
Values are ORs per SD increase in serum or urinary metabolites
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