Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy

Eur J Ophthalmol. Jan-Feb 2011;21(1):48-54. doi: 10.5301/ejo.2010.4447.


Purpose: Advanced glycation end products (AGEs) accumulation may result from chronic hyperglycemia promoting generation and onset of microangiopathy. The aim of this study was to investigate the association between diabetic retinopathy (DR) and levels of AGEs, pentosidine, and N-carboxymethyl-lysine (CML) in aqueous humor and serum of human patients and their role in predicting the progression of DR.

Methods: Ninety patients with type 2 diabetes mellitus and 30 nondiabetic patients underwent cataract surgery. The diabetic group was divided into 3 subgroups: 35 patients with mild nonproliferative diabetic retinopathy (mild NPDR), 30 patients with severe nonproliferative diabetic retinopathy (severe NPDR), and 25 patients with proliferative diabetic retinopathy (PDR). In the samples, pentosidine was measured by high-performance liquid chromatography and CML using a competitive enzyme-linked immunosorbent assay.

Results: Serum levels of pentosidine and CML were significantly increased in patients with type 2 diabetes compared to nondiabetic controls (p<0.001). In diabetic patients, serum pentosidine and CML levels were significantly higher in patients who had PDR than in those with mild NPDR or severe NPDR (both p<0.001). A significant difference was found between aqueous humor CML levels in diabetic and nondiabetic patients and increased along with progression of DR. Significant correlations existed between serum pentosidine and aqueous CML in severe NPDR and PDR (p<0.001).

Conclusions: In patients with type 2 DM, serum levels of pentosidine and CML are related to severity of retinopathy. In addition, aqueous humor level of CML increased along with progression of DR. Pentosidine and CML can be used as biochemical markers of glycoxidation and related to onset or progression of DR.

MeSH terms

  • Adult
  • Aged
  • Aqueous Humor / metabolism
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers / blood*
  • Blood Glucose / metabolism
  • Cataract Extraction
  • Chromatography, High Pressure Liquid
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / classification
  • Diabetic Retinopathy / diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycated Hemoglobin A / metabolism
  • Glycation End Products, Advanced / blood*
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / blood
  • Male
  • Middle Aged
  • Visual Acuity


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • hemoglobin A1c protein, human
  • N(6)-carboxymethyllysine
  • Arginine
  • pentosidine
  • Lysine