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

FEBS Lett. 2019 Jul;593(13):1598-1615. doi: 10.1002/1873-3468.13495. Epub 2019 Jun 28.


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.

Keywords: HNF1A-MODY; N-glycosylation; glycosyltransferase; type 1 diabetes; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism*
  • Glycosylation / drug effects
  • Hexosamines / biosynthesis
  • Humans
  • Molecular Targeted Therapy / methods*
  • Nitrogen / metabolism


  • Biomarkers
  • Hexosamines
  • Nitrogen