Association of increased levels of MCP-1 and cathepsin-D in young onset type 2 diabetes patients (T2DM-Y) with severity of diabetic retinopathy

J Diabetes Complications. 2017 May;31(5):804-809. doi: 10.1016/j.jdiacomp.2017.02.017. Epub 2017 Mar 10.

Abstract

Aim: Young onset type 2 diabetes patients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy.

Methods: In this case-control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35). Clinical characterization of the study subjects was done by standard procedures and MCP-1 and cathepsin-D were measured by ELISA.

Results: Compared to control individuals, patients with T2DM-Y, NPDR and PDR exhibited significantly (p<0.001) higher levels of MCP-1. Cathepsin-D levels were also significantly (p<0.001) higher in patients with T2DM-Y without and with diabetic retinopathy. Correlation analysis revealed a positive association (p<0.001) between MCP-1 and cathepsin-D levels. There was also a significant negative correlation of MCP1/cathepsin-D with C-peptide levels. The association of increased levels of MCP-1/cathepsin-D in patients with DR persisted even after adjusting for all the confounding factors.

Conclusion: As both MCP-1 and cathepsin-D are molecular signatures of cellular senescence, we suggest that these biomarkers might be useful to predict the development of retinopathy in T2DM-Y patients.

Keywords: Biomarkers; Cathepsin-D; Diabetic Retinopathy; MCP-1; T2DM-Y.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • C-Peptide / blood
  • Case-Control Studies
  • Cathepsin D / blood*
  • Chemokine CCL2 / blood*
  • Confounding Factors, Epidemiologic
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • India
  • Male
  • Reproducibility of Results
  • Risk Factors
  • Severity of Illness Index
  • Up-Regulation*
  • Young Adult

Substances

  • Biomarkers
  • C-Peptide
  • CCL2 protein, human
  • Chemokine CCL2
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • CTSD protein, human
  • Cathepsin D

Supplementary concepts

  • Maturity-Onset Diabetes of the Young, Type 2