Biomarkers of Oxidative DNA Damage and Soluble Fas/Fas Ligand in Type 2 Diabetic Patients

Abstract

Problem statement: Involvement of oxidative stress in the pathogenesis of diabetic complications has been proposed. 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. Apoptosis via Fas/Fas Ligand (FasL) interactions has been proposed to be a major T-cell-mediated effector mechanism in autoimmune diabetes. This study was undertaken to investigate whether the serum levels of 8-OHdG and circulating soluble Fas/Fas Ligand, two transmembrane glycoproteins involved in apoptosis, are altered in patients with type 2 diabetes. Approach: 8-OHdG, sFas and sFasL were measured with the ELISA method in twenty normal controls (group I), thirty patients with type 2 DM (duration ranged from 1-3 years, group II) and in thirty patients with type 2 DM (duration ranged from 5-10 years, group III). Also, serum glucose (Fasting and postprandial), HbA1c, insulin, lipid profile (total cholesterol, triacylglycerol, HDL-c and LDL-c) and serum malondialdehyde (MDA) level were determined. Results: The patients with a long duration of diabetes were poorly controlled and had significantly higher levels of HbA1c (p<0.05) when compared to control group. Serum levels of total cholesterol, triacylglycerol and LDL-c were significantly higher (p<0.05) in diabetic patients in comparison with healthy normal control, while HDL-c level was significantly lower in both groups than in the control group (p<0.05). 8-OHdG and MDA levels were significantly higher in both diabetic groups than in the control group. sFas serum levels were significantly increased in both diabetic groups as compared with normal controls (10.5±3.2, 14.4±3.4 ng mL^-1 Vs 4.5±2.1 ng mL^-1, p<0.05), but the levels were significantly higher in patients with long duration of diabetes when compared with that of short duration of diabetes (p<0.05). sFasL serum levels were less than 0.1 ng mL^-1 in normal control group and the same results were observed in sera from groups of diabetic patients. A significant positive correlation was observed between 8-OHdG and each of HbA1c, MDA, HOMA index and sFas in diabetic group of long duration. On the other hand, there was a positive correlation between sFas levels and each of HbA1c, MDA and HOMA index. Also MDA was positively correlated with HbA1c and HOMA index. HbA1c was positively correlated with HOMA index. Conclusion: In type 2 diabetic patients, 8-OHdG could be a sensitive biomarker for evaluating oxidative DNA damage, there seems to be a dysregulation of apoptosis, as expressed by enhanced sFas levels, suggesting that these markers may be helpful for the early diagnosis of type 2 diabetic patients.