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 ß-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.

Abnormal glucose tolerance in children with cystic fibrosis: the predictive role of continuous glucose monitoring system.

UNLABELLED: A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood. OBJECTIVE: The aims of the study were to compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in the diagnosis of altered glucose metabolism, and to longitudinally evaluate the role of CGMS in predicting glucose metabolism deterioration in children with CF. METHODS: Seventeen children with CF and 14 controls were enrolled (mean age 13.3+/-3.0 years). All subjects underwent OGTT and CGMS registration. On the basis of OGTT, children were classified as normal glucose tolerance, impaired glucose tolerance (IGT), IGT plus at least one glucose value above 200 mg/dl at intermediate OGTT points (IGT+200) and CF-related diabetes (CFRD). HbA1c, glucose area under the curve, insulin sensitivity, and insulinogenic and disposition indexes were also considered. Subjects with CF underwent another OGTT after 2.5 years. RESULTS: Baseline OGTT revealed 3/17 (7.6%) children with CF with at least one glucose value above 200 mg/dl (1 CFRD and 2 IGT+200), while CGMS revealed 6/17 (35.3%) children with glucose excursions above 200 mg/dl (P=0.010). None of the controls showed glucose over 200 mg/dl either at OGTT or at CGMS. At the 2.5-year follow-up OGTT, all the six subjects who had diabetic glucose excursion (i.e. >200 mg/dl) at baseline CGMS presented IGT+200 or CFRD. In logistic regression analysis, CGMS diabetic excursion was the strongest predictor of IGT+200 and CFRD (P<0.001). CONCLUSIONS: CGMS could be a useful tool to predict glucose metabolism derangements in children affected by CF.