414-P: Multiomic Plasma Markers of Diabetic Kidney Disease in Type 1 Diabetes

Diabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). We investigated whether metabolomic, lipidomic and proteomic plasma markers were associated with albuminuria in the Coronary Artery Calcification in Type 1 Diabetes cohort. Two timed overnight urine collections were performed, and albumin excretion rates (AER) were averaged. If overnight samples were unable to be obtained, a spot urine sample was collected and albumin/creatinine ratio (ACR) was used to determine albuminuria status. Albuminuria was defined as an AER ≥ 20 ug/min or an ACR ≥ 30mg/g. Plasma samples from the baseline examination were assayed by LC-MS for multiple omics markers in 225 participants with T1D. Moderated t-tests using false discovery rate (FDR) adjustment for multiple comparisons were used to examine the markers associated with albuminuria presence. An FDR adjusted p-value <0.05 was considered to be statistically significant. Average ± SD for age was 36 ± 9 years and for diabetes duration was 23 ± 9 years, and 58% [n = 120] were female. The prevalence of albuminuria at baseline was 20.4% (n = 46). There were 15 metabolite markers (3 metabolites of symmetric dimethylarginine, 2 of glycyl-glycine, and one each of aspartyl-glycine, glycyl-aspartate and 1-methylhistidine, 7 uncertain) with higher expression in participants with DKD than in those without DKD. There were 7 lipid markers in the acylcarnitine family that were elevated in participants with DKD compared to those without DKD, and 19 glycated peptides (16 in fibrinogen, 1 in kininogen and 1 in hemopexin) showed higher expression in participants with DKD than in those without DKD. None of the unmodified proteins differed by DKD status. Multiple omics markers were higher in T1D participants with albuminuria than in people without any sign of DKD. These findings may suggest changes in lipids, metabolites and glycated proteins early in the course of DKD, and these markers should be explored as potential predictors of worsening DKD.