Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications.
The aims of the study were to ascertain the potential role of oxidative stress in the onset of disease-related pathophysiological complications in young type 1 diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation, and changes in antioxidant defense system status were measured in blood samples from 26 young diabetic patients with recently diagnosed (< 6 months) microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40 healthy age-matched controls (CR). Both diabetic groups presented similar fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte glutathione peroxidase activity, glutathione content, and plasma beta-carotene to be significantly lower in diabetic patients compared with control subjects, but with no significant differences between -DC and +DC groups. Antioxidant enzyme superoxide dismutase activity was significantly higher in the erythrocytes of diabetic patients independently of the presence of microvascular complications. However, the plasma alpha-tocopherol/total lipids ratio was significantly diminished in +DC group compared with -DC (p =.008). Lipid peroxidation indices measured in plasma included malondialdehyde, lipid hydroperoxides, and lipoperoxides, which were significantly elevated in our diabetic patients regardless of the presence of complications. Evidence of oxidative damage to proteins was shown both through the quantification of plasma protein carbonyl levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those of controls (0.32 +/- 0.03 mmol/mg prot; p <.01) and immunoblot analysis of protein-bound carbonyls. Additionally, a marked increase in protein oxidation was observed in +DC patients through assessment of advanced oxidation protein products (AOPP) considered to be an oxidized albumin index; AOPP values were significantly higher in +DC than in -DC patients (p <.01) and CR (p <.0001). These results point to oxidatively modified proteins as a differential factor possibly related to the pathogenesis of diabetic complications.
Martín-Gallán
Pilar
P
Biochemistry and Molecular Biology Center, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
Carrascosa
Antonio
A
Gussinyé
Miguel
M
Domínguez
Carmen
C
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis*; D001798:Blood Proteins / Q000737:chemistry; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism; D019207:beta Carotene / Q000097:blood
D000975:Antioxidants; D015415:Biomarkers; D001798:Blood Proteins; D005978:Glutathione; D005979:Glutathione Peroxidase; D006442:Glycated Hemoglobin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; D019207:beta Carotene