N-glycan as new potential biomarker for predicting treatment response in patients with type 2 diabetes mellitus

Biomark Med. 2024 Dec;18(24):1113-1122. doi: 10.1080/17520363.2024.2432309. Epub 2024 Nov 25.

Abstract

Aims: To investigate the N-glycans related to the metformin efficacy in patients with type 2 diabetes mellitus (T2DM).

Materials and methods: We enrolled 141 healthy controls and 195 newly diagnosed T2DM patients treated with metformin for 3 months. Serum N-glycan profile was determined by DNA sequencer - assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). The N-glycan model was established by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was used to analyze the predictive power of the N-glycan model for metformin efficacy.

Results: The abundances of several N-glycans in serum of T2DM patients at baseline were significantly different from those of healthy controls and tended to recover the N-glycan of controls after 3 months treatment. Serum N-glycans changes were more significant in the good response group (FPG <7 mmol/L) after metformin treatment. In addition, the abundance of peak9 at baseline had an opposite tendency between HbA1c increased and decreased groups post-treatment, which could be a biomarker for predicting metformin efficacy. Peak9 combined with other 11 N-glycans at baseline was used to establish the predictive model to distinguish non-response from response patients (AUROC = 0.780, sensitivity = 70.6% and specificity = 77.5%).

Conclusions: Serum N-glycans may have potential value as biomarkers for indicating the efficacy of metformin.

Keywords: N-glycan biomarker; clinical indicators; metformin; treatment response; type 2 diabetes mellitus.

MeSH terms

  • Adult
  • Aged
  • Biomarkers* / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Polysaccharides* / blood
  • ROC Curve
  • Treatment Outcome

Substances

  • Polysaccharides
  • Metformin
  • Biomarkers
  • Hypoglycemic Agents
  • Glycated Hemoglobin

Grants and funding

This work was supported by the Major Science and Technology Special Project of China Thirteenth Five-year Plan ([2018ZX10732401-003-015] and the project of Peking University - SysDiagno Biotech Joint Laboratory of Glycomics.