Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications

Abstract

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.

Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study

“…diabetes is supported by evidence from animal models, and 8-oxoGuo has been found to be a more sensitive nucleic acid marker of diabetes morbidity and mortality than 8-oxodG (28). Moreover, a cross-sectional study indicated notably higher 8-oxoGuo levels in patients with type 2 diabetes with diabetic macrovascular complications, as well as higher 8-oxodG levels (although to a lesser extent) (29).…”

Urinary Markers of Oxidative Dna Damage in Type 1 Diabetic Children: Relation to Microvascular Complications

“…Again, we can refer the previous diabetic microvascular complications to the oxidative damage that happens when the ROS level overpowers defensive mechanisms, leading to a cellular imbalance between pro-and antioxidant factors [32]. Elevated levels of oxidation markers such as 8-oxodG most likely prompt to strand breaks and oxidative base changes; and multiple signaling pathways that may likewise add to the unfavorable impacts of glucotoxicity on cellular functions [33,34].…”

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

“…OS‐induced damage to DNA also contributes to neurodegeneration, promoting Parkinson's disease, Alzheimer's disease, and sporadic amyotrophic lateral sclerosis . Other health disorders arising from oxidative damage to DNA are cardiovascular diseases, Wilson's disease, Huntington's disease, inflammatory bowel disease, acquired immunodeficiency syndrome, diabetes and its complications, chronic obstructive pulmonary disease, and rheumatoid arthritis …”

“…6 OS-induced damage to DNA also contributes to neurodegeneration, promoting Parkinson's disease, [7][8][9] Alzheimer's disease, [10][11][12] and sporadic amyotrophic lateral sclerosis. 13 Other health disorders arising from oxidative damage to DNA are cardiovascular diseases, [14][15][16][17] Wilson's disease, 18,19 Huntington's disease, 20,21 inflammatory bowel disease, 22,23 acquired immunodeficiency syndrome, 24,25 diabetes 26 and its complications, [27][28][29] chronic obstructive pulmonary disease, 30 and rheumatoid arthritis. [31][32][33] The hydroxyl radical (˙OH) has been held responsible for the most common oxidative damage to DNA, 34,35 which involves different chemical routes and yields diverse products (Scheme 1).…”