434-P: Urinary Proteome Classifiers in Prediabetes Clusters

Objective: Patients with prediabetes have recently been classified into 6 prediabetes clusters, that stratify the risk of diabetes and complications. Cluster 1, 2 and 4 are low risk-clusters while cluster 3, 5 and 6 are high-risk clusters. Of notice, especially patients of cluster 6 have an elevated risk of nephropathy despite their low diabetes risk. To investigate if differences across clusters can be captured from urine peptidome, we studied differences in pre-specified urinary peptidome classifiers across age and sex matched participants from 6 prediabetes clusters (n=249, median age 46 (IQR 39 - 54) years, BMI 30.4 (26.9 - 39.4) kg/m², HbA1c 5.5 (5.3 - 5.8) %). Methods: Peptides in spot urine samples collected at the University Hospital Tuebingen from 11/2004 to 11/2012 were investigated using capillary electrophoresis coupled mass spectroscopy. The following classifiers based on multiple urine peptides had been developed to detect different conditions and were assessed: CKD273 (chronic kidney disease, CKD), validated in a large clinical cohort), HF1 and HF2 (heart failure), CAD238 (coronary artery disease, CAD), Col_death (collagen type-1 turnover), solid_tumor (solid tumor). Matsuda index and NEFA insulin sensitivity index (ISI) were used for estimation of insulin sensitivity. Results: The urinary peptidome classifiers CKD273, HF2 and CAD238 were significantly different between prediabetes clusters, with elevated values in cluster 6 compared to the healthiest cluster 2. These classifiers also correlated with Matsuda index and NEFA ISI. Classifiers HF1, Col_death and solid_tumor did not associate with prediabetes clusters or insulin sensitivity indices. Conclusions: Beyond corroboration of a previously described increased risk of CKD, urinary peptidome classifiers suggest elevated risk of heart failure and coronary artery disease in persons of the prediabetes cluster 6. This could underlie increased mortality in this group, independent of diabetes development.