The Association Between Subclinical Atherosclerosis Serum Markers and Oxidative DNA Damage in Normoglycemic Normotolerant Offspring of Diabetic Parents

• Published in: Journal of diabetes Vol. 17; no. 8; pp. e70133 - n/a
• Main Authors: Rahimi, Masoumeh, Soufi, Farhad Ghadiri, Koochakkhani, Shabnaz, Rahnama Inchehsablagh, Behnaz, Azarbad, Abnoos, Mahmoudi, Masoumeh, Kheirandish, Masoumeh, Mashayekhi, Farideh Jalali, Eftekhar, Ebrahim
• Format: Journal Article
• Language: English
• Published: Melbourne Wiley Publishing Asia Pty Ltd 01.08.2025; John Wiley & Sons, Inc
• Subjects: 8-Hydroxy-2'-Deoxyguanosine; 8‐OHdG; Adult; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - genetics; Biomarkers - blood; Blood Glucose - analysis; Blood Glucose - metabolism; Case-Control Studies; Child of Impaired Parents; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; DNA Damage; E-Selectin - blood; Female; Glucose; Glucose Intolerance - blood; Glucose Intolerance - genetics; Humans; ICAM‐1; Intercellular Adhesion Molecule-1 - blood; Lipoproteins, LDL - blood; Male; Middle Aged; offspring of diabetics; Original; Oxidative Stress; ox‐LDL; atherosclerosis; 8‐OHdG; ICAM‐1; offspring of diabetics; ox‐LDL
• ISSN: 1753-0393; 1753-0407; 1753-0407
• DOI: 10.1111/1753-0407.70133

ABSTRACT Introduction It has been shown that offspring of type 2 diabetic parents have a high risk for developing diabetes and atherosclerosis, but the exact mechanism is unclear. In the present study, the possible association between oxidative stress and subclinical atherosclerosis serum markers in this population was investigated. Method LDL/HDL ratio, triglyceride‐glucose index (TyG), atherogenic index of plasma (AIP), single‐point insulin sensitivity estimator (SPISE) index, oxidized LDL (Ox‐LDL), intercellular adhesion molecules (ICAM‐1 and E‐selectin), as well as the marker of oxidative DNA damage were compared among 150 offspring of diabetic parents (90 normoglycemic and normotolerant offspring, 31 offspring with impaired fasting glucose (IFG), and 29 offspring with impaired glucose tolerance (IGT)), and 40 age‐and sex‐matched healthy control individuals. The control subjects were among individuals with no family history of diabetes. Results All three groups with diabetic parents, that is, norm‐offspring, IFG, and IGT groups, had higher serum levels of Ox‐LDL, ICAM‐1, and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) than the controls. In the whole population, ICAM‐1 correlated with Ox‐LDL, fasting plasma glucose (FPG) and 8‐OHdG, and Ox‐LDL correlated with LDL/HDL, fasting plasma glucose, TyG index, and 8‐OHdG after adjustment for age, sex, and BMI. Conclusion This study shows that subclinical atherosclerosis and oxidative DNA damage are present in normotolerant normoglycemic offspring of type 2 diabetic parents, and they progress with impaired fasting glucose and/or impaired glucose tolerance. Also, our results indicate that a marker of subclinical atherosclerosis, ICAM‐1, was directly correlated with the DNA damage marker, 8‐OHdG. Proposed molecular mechanism linking reactive oxygen species‐driven mitochondrial dysfunction to atherosclerosis in offspring of diabetic individuals. (1) Mitochondrial dysfunction (due to genetic susceptibility and hyperglycemia) overproduces reactive oxygen species (ROS). (2) ROS induce DNA damage (elevated 8‐OHdG) and activate PARP‐1, depleting NAD+ and impairing endothelial function. (3) NF‐KB activation upregulates adhesion molecules (E‐selectin, ICAM‐1) and the LOX‐1 receptor, amplifying vascular inflammation. (4) The Ox‐LDL/LOX‐1 vicious cycle promotes foam cell formation and atherosclerotic plaque progression.