Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy

Can J Diabetes. 2017 Feb;41(1):82-89. doi: 10.1016/j.jcjd.2016.07.007. Epub 2016 Dec 1.


Objectives: The present study aimed to evaluate the role of hyperlipidemia in increased formation of advanced lipoxidation end products (ALEs) and to evaluate whether there is any relationship between ALEs generation and erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity in cases of mild nonproliferative diabetic retinopathy (MNPDR).

Methods: In this study, we enrolled 100 patients with type 2 diabetes and MNPDR, 100 subjects with type 2 diabetes but without retinopathy (DNR) and 90 normal individuals without diabetes as healthy controls (HCs). Erythrocyte nicotinamide dinucleotide phosphate (NADPH), G6PD activity, serum total cholesterol, low- and high-density lipoprotein (LDL, HDL) and triglyceride levels were determined by photometric assay. Serum malondialdehyde (MDA) protein adduct and hexanoyl-lysine (HEL) were measured by an enzyme-linked immunosorbent assay (ELISA).

Results: A robust linear relationship was observed between MDA protein adduct and LDL or cholesterol or triglyceride levels, and HEL and LDL or cholesterol or triglyceride levels in subjects with MNPDR (p=0.0001). A significant inverse association was observed between erythrocyte G6PD activity and serum MDA protein adductor HEL levels in subjects with MNPDR (p=0.0001).

Conclusions: Hyperlipidemia is an important factor that is associated with increased ALEs formation in persons with MNPDR. Increased ALEs generation was associated with decreased G6PD activity and low NADPH levels in cases of MNPDR, suggesting their detrimental role in the occurrence of early NPDR.

Keywords: advanced lipoxidation end products (ALEs); diabetic retinopathy; glucose-6-phosphate dehydrogenase (G6PD); glucose-6-phosphate-déshydrogénase (G6PD); hyperlipidemia; hyperlipidémie; mild nonproliferative diabetic retinopathy (MNPDR); nicotinamide-adénine-dinucléotide phosphate réduit (NADPH); produits finaux de la lipoxidation avancée (ALE pour advanced lipoxidation end products); reduced nicotinamide adenine di nucleotide phosphate (NADPH); rétinopathie diabétique; rétinopathie diabétique non proliférante minime (RDNP minime).

MeSH terms

  • Adult
  • Advanced Oxidation Protein Products / blood*
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / epidemiology
  • Erythrocytes / metabolism*
  • Female
  • Glucosephosphate Dehydrogenase / blood*
  • Humans
  • Hyperlipidemias / blood*
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / epidemiology
  • Male
  • Middle Aged
  • Oxidation-Reduction


  • Advanced Oxidation Protein Products
  • Biomarkers
  • Glucosephosphate Dehydrogenase