Levels of Oxidative DNA Damage are Correlated With Duration of Type 1 Diabetes

Under conditions of oxidative stress damage can occur to all cellular biomolecules, including lipids, proteins, carbohydrates and DNA. Such damage has been implicated in the pathogenesis and long-term complications of Type I diabetes mellitus. Levels of oxidative DNA damage in eight well controlled Type I diabetic subjects (mean HbA1c 7.03  0.10) and eight age and sex matched control’s (mean HbA1c 4.58  0.06) were compared using the modified comet assay. DNA strand breaks, oxidised pyrimidines (endonuclease III sensitive-sites) and ring-opened purines as well as 8-oxo-guanine (formamidopyrimidine glycosylase sensitive-sites) were measured. The results failed to demonstrate a statistically significant difference in the mean levels of oxidative DNA damage in Type I diabetic subjects (mean endonuclease III 9.77  2.6; mean formamidopyrimidine glycosylase 13.08  2.3) compared to control subjects (mean endonuclease III 12.19  2.2; mean formamidopyrimidine glycosylase 12.48  1.4). However linear regression analysis revealed a statistically significant (p = 0.024) positive correlation between the number of formamidopyrimidine glycosylase sensitive-sites and duration of Type I diabetes mellitus. In addition a positive correlation was observed between the number of endonuclease III sensitive-sites and duration of Type I diabetes mellitus, though this was not significant (p = 0.078). These results indicate that even with good glycaemic control there was a positive correlation between levels of oxidative DNA damage and duration of Type I diabetes in vivo. The physiological effect(s) of this DNA damage remain to be elucidated.