Proteomics for personalized medicine in type 2 diabetes mellitus

Abstract

Diabetes mellitus (DM) is a metabolic disease associated with a number of metabolic disturbances including glucose, lipid, and protein metabolism. A multifaceted interplay of genetic, environmental, and socioeconomic factors contributes to increasing prevalence of DM. Robust efforts have been made to build and strengthen the healthcare systems for the diagnosis and management of DM. However, it remains a medical dilemma how to effectively monitor and manage DM. At present, blood glucose is the gold standard biomarker in the diagnosis and management of DM. The values of blood in monitoring the occurrence and progression of DM have not been well explored. To fully understand the biological changes in the blood of DM patients, we recruited 60 participants including 30 healthy adults and 30 patients diagnosed with DM. By performing deep profiling of proteomes in the blood, we identified a total of 42 proteins that are differentially expressed in the blood of diabetic patients compared with healthy controls. Of the differentially expressed proteins, α2-macroglobulin, L-selectin, APOA1 and APOD could serve as a more sensitive combinational biomarker in distinguishing diabetic patients and healthy controls and may predict the progression of DM. Furthermore, through analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways associated with the differentially expressed proteins, we discovered that the activation of liver X receptors/retinoid X receptors in diabetic patients was a key biological event that triggers the dysregulation of cholesterol, lipid, and glucose metabolism. Collectively, our study provides a rich and open-access data resource to shed lights on personalized strategies for optimal management of DM.