Evidence for augmented oxidative stress in the subjects with type 1 diabetes and their siblings: a possible preventive role for antioxidants

Abstract

BACKGROUND/OBJECTIVES: Oxidative stress (OS) is thought to be involved in both development of type 1 diabetes (T1D) and its further complications. In this study, certain biomarkers of OS were compared among the subjects with T1D, their non-diabetic siblings and unrelated healthy controls. SUBJECTS/METHODS: Known cases of T1D from both sexes aged 5-25 years were enrolled in a case-control study (n 1 ¼ 60). There were two control groups; non-diabetic siblings (n 2 ¼ 60) and unrelated apparently healthy subjects (n 3 ¼ 60). Anthropometric, dietary and laboratory assessments were done. RESULTS: There was no significant difference in dietary data among the groups. Total antioxidant capacity was significantly lower in T1D than both related and unrelated controls (1.6±0.05, 1.7±0.05 and 1.8±0.06 mmol BSA equivalent/l, respectively, P ¼ 0.044). Both T1D subjects and their siblings showed lower glutathione peroxidase (GSH-px) levels (median (interquartile range): 22.2 (28.6), 29.9 (23) and 41.8 (73.6) U/ml, respectively, P ¼ 0.006). On the contrary, superoxide dismutase concentrations were significantly higher in T1D group and the siblings than unrelated healthy controls (243 (45.3), 157.8 (176.9) and 27.9 (8.7) U/l, respectively, Po0.001). Serum concentrations of GSH correlated with energy intake in the siblings (r ¼ 0.521, Po0.001) and unrelated controls (r ¼ 0.268, P ¼ 0.042) but not in T1D group. The associations remained significant after controlling for blood glucose (r ¼ 0.437, P ¼ 0.001 and r ¼ 0.420, P ¼ 0.011, respectively) in both the groups. CONCLUSION: Augmented OS in the siblings may indicate an increased requirement for antioxidants in genetically diabetes-prone subjects.

Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes

“…Moreover, beta cell viability is reduced after oxidative stress in H 2 O 2 or NO treated human islets (93). Consistent with these observations, serum levels of GPx and SOD are reduced in patients with T1D compared to healthy subjects (94). Thus, antioxidants may possess anti-diabetic potential in NOD murine model (95, 96) supporting this therapeutic strategy in patients with T1D (97, 98).…”

New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes

“…Treatment of nonobese diabetic (NOD) mice with glycolysis inhibitors resulted in delayed T1D onset and protected b-cell mass (24). In addition, as part of the OXPHOS program, the movement of electrons generates a substantial amount of reactive oxygen species (ROS) (25). The role of ROS in controlling the differentiation of T cells by modulating metabolism has recently been described (21,(25)(26)(27)(28)(29)(30).…”

“…In addition, as part of the OXPHOS program, the movement of electrons generates a substantial amount of reactive oxygen species (ROS) (25). The role of ROS in controlling the differentiation of T cells by modulating metabolism has recently been described (21,(25)(26)(27)(28)(29)(30). Investigators have shown that ROS can act as signaling molecules involved in the process of T cell activation, proliferation, and function (26).…”

Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet β cells

“…A complex interplay between genetic and environmental factors leads to the autoimmune attack of the ␤ cells, and recent studies suggest that ␤ cell dysfunction may contribute to neoantigen formation, which instigates autoimmunity (2)(3)(4). Oxidative stress resulting from an imbalance in favor of oxidants over antioxidants has been suggested as a primary cause of ␤ cell dysfunction in T1D (5)(6)(7). Because of their role in the production and release of insulin, ␤ cells generate endogenous reactive species such as hydrogen peroxide, hydroxyl radicals, and peroxynitrites.…”