All glutathione forms are depleted in blood of obese and type 1 diabetic children.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of type 1 diabetes (T1D), where an increase in reactive oxygen species may contribute to the initial destruction of β-cells. Accumulating evidence also suggests a role for oxidative stress in obesity, where it may potentiate the development of complications.
OBJECTIVE: To analyze the in vivo homeostasis of glutathione in children with T1D at onset and in children who are obese, to evaluate the systemic content of all glutathione forms (total, reduced, oxidized, and protein-bound glutathione) and the balance among them. Moreover, since glutathione bound to hemoglobin is a clinical marker of oxidative stress in human blood, we analyzed glutathionyl-hemoglobin in T1D and in obese children.
SUBJECTS: Children with T1D at onset (n = 30) or obesity (n = 30) at the first observation, and 30 healthy subjects chosen from the children who attended the outpatient clinic for minor problems.
METHODS: We assessed circulating levels of various glutathione forms by performing reverse-phase high performance liquid chromatography. Glutathionyl-hemoglobin analysis was carried out by cation-exchange chromatography.
RESULTS: In children with T1D and in obese children, we found a significant decrease of all glutathione forms including, for the first time, the content of total glutathione and glutathionylated proteins. The comparison among forms shows no significant imbalance in T1D patients, whereas in obese children it seems to suggest an attempt to rebalance the glutathione system homeostasis.
CONCLUSIONS: Our findings consistently show in vivo evidence of glutathione depletion upon early onset of T1D and in obese children, thus evidencing glutathione as an early marker in these two metabolic conditions.