Altered N-glycosylation profiles as potential biomarkers and drug targets in diabetes.

N-glycosylation is a ubiquitous protein modification, and N-glycosylation profiles are emerging as both biomarkers and functional effectors in various types of diabetes. Genome-wide association studies identified glycosyltransferase genes as candidate causal genes for type 1 and type 2 diabetes. Studies focused on N-glycosylation changes in type 2 diabetes demonstrated that patients can be distinguished from healthy controls based on N-glycome composition. In addition, individuals at an increased risk of future disease development could be identified based on N-glycome profiles. Moreover, accumulating evidence indicates that N-glycans have a major role in preventing the impairment of glucose-stimulated insulin secretion by maintaining the glucose transporter in proper orientation, indicating that interindividual variation in protein N-glycosylation might be a novel risk factor contributing to diabetes development. Defective N-glycosylation of T cells has been implicated in type 1 diabetes pathogenesis. Furthermore, studies of N-glycan alterations have successfully been used to identify individuals with rare types of diabetes (such as the HNF1A-MODY), and also to evaluate functional significance of novel diabetes-associated mutations. In conclusion, both N-glycans and glycosyltransferases emerge as potential therapeutic targets in diabetes.