1252-P: Differences in Cardiometabolic and Immune Biomarkers between Novel Subphenotypes of Individuals at Elevated Risk for Type 2 Diabetes

Abstract

Recent efforts to address heterogeneity among individuals at elevated risk for type 2 diabetes (T2D) have focused on metrics derived from oral glucose tolerance tests, body fat distribution, and hepatic fat content to subphenotype and stratify patients. A novel classification scheme identified six subphenotypes with significantly distinct risks of developing T2D, complications of insulin resistance, and mortality. The aim of our study was to evaluate differences in cardiometabolic and immune biomarkers among these clusters. Fasting serum levels of 5 Olink targeted protein panels (Cardiovascular III, Cardiometabolic, Immune response, Inflammation, Metabolism) comprising 460 oligo-species were measured in 1,597 individuals without diabetes from the Bialystok PLUS study and the Polish Registry of Diabetes. Pairwise differences between subgroups for biomarkers were assessed with generalized linear mixed models, with and without adjustment for the clustering variables. In the unadjusted model, 164 biomarkers showed significantly different levels among clusters (q-value < 0.05), whereas the adjusted model identified 166 significantly different biomarkers. Generally, cluster 2 (lowest T2D and mortality risk) had a more favorable profile of cardiometabolic and immune biomarkers, with clusters 5 and 6 (high-risk) showing more unfavorable profiles. Among significant biomarkers, the greatest differences were observed for tissue-type plasminogen activator and fatty acid binding protein 4, with lowest levels in cluster 2 and highest levels in clusters 5 and 6. Insulin-Like Growth Factor Binding Protein 1 and Paraoxonase 3 showed the greatest differences in the opposite direction. Our study shows that clusters of individuals at elevated risk for T2D stratify across orthogonal axes of cardiometabolic and immune biomarkers, underlining a prominent independent role of these pathways in the pathophysiology of novel subtypes. Disclosure L.Szczerbinski: None. P.Sowa: None. I.Kowalska: None. K.A.Kaminski: Other Relationship; AstraZeneca, Boehringer Ingelheim Inc. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. A.J.Kretowski: None. A.Janucik: None. W.Kwedlo: None. P.Konopka: None. A.Citko: None. A.Paszko: None. M.Taylor: None. M.Czajkowski: None. M.Kondraciuk: None.