Oxidative DNA damage in diabetes mellitus: its association with diabetic complications

Diabetologia. 1999 Aug;42(8):995-8. doi: 10.1007/s001250051258.

Abstract

Aims/hypothesis: Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2'-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the pathogenesis of diabetic complications, we measured the content of 8-oxo, 2'-deoxyguanosine in the urine and the blood mononuclear cells of Type II (non-insulin-dependent) diabetic patients.

Methods: We studied 53 Type II diabetic patients and 39 age-matched healthy control subjects. We assayed 8-oxo, 2'-deoxyguanosine by HPLC-electrochemical detection method.

Results: The content of 8-oxo, 2'-deoxyguanosine in the urine and the mononuclear cells of the Type II diabetic patients was much higher than that of the control subjects. Urinary 8-oxo, 2'-deoxyguanosine excretion and the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells from the diabetic patients with complications were higher than those from the diabetic patients without complications. Urinary excretion of 8-oxo, 2'-deoxyguanosine was significantly correlated with the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells. The 8-oxo, 2'-deoxyguanosine content in the urine and mononuclear cells was correlated with the haemoglobin A1c value.

Conclusions/interpretation: This is the first report of a direct association between oxidative DNA damage and the complications of diabetes. The augmented oxidative DNA damage in diabetes is speculated to contribute to the pathogenesis of diabetic complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Analysis of Variance
  • Biomarkers / analysis
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / analysis
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / physiopathology*
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / physiopathology*
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Reference Values
  • Smoking

Substances

  • Biomarkers
  • Glycated Hemoglobin A
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine