Proteomic Profiling of Glucose Metabolism Disturbances Yields Novel Plasma Proteins that May Be Associated With Development or Early Complications of Diabetes

Postprandial variability in glucose and protein levels is one of the elements of insulin resistance (IR) and prediabetes, which area prelude to type 2 diabetes mellitus (DM). The objective of the study was a comprehensive proteomic analysis according to glucose tolerance in the general population who did not self-report DM or other serious diseases. We used Olink® Reveal, a novel, high-throughput platform by Olink Proteomics based on their Proximity Extension Assay (PEA) to identify levels of 1034 circulating proteins in small volumes of plasma samples. The study enrolled 508 participants (mean age 52 ± 10.5 years, 47.2% men) from the Polish population-based Bialystok PLUS study. The study population was categorized according to glucose metabolism in comparison to impaired fasting blood glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed DM. Analysis of variance (ANOVA) adjusted for age, weight, fat mass, lean mass, and body mass index (BMI), identified 19 proteins significantly associated with categories of glucose tolerance. A linear regression model adjusted for the same confounding factors showed statistically significant associations between Hb _A1c levels and 37 proteins. Our findings highlight multiple proteins with significantly different levels across categories of glucose tolerance, especially between the healthy controls and the group with newly diagnosed DM. The consistent patterns of protein level differences, independently of body composition, suggest potential involvement in progression of glucose metabolism disturbances, and provide unique insights into pathomechanisms.