Oxidative DNA damage in diabetes mellitus: its association with diabetic complications.
OBJECTIVE
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
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.
Hinokio
Y
Y
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Suzuki
S
S
Hirai
M
M
Chiba
M
M
Hirai
A
A
Toyota
T
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012016:Reference Values; D012907:Smoking
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D003849:Deoxyguanosine; D006442:Glycated Hemoglobin