OBJECTIVE -This study assesses the effects of insulin pump therapy on diabetes control and family life in children 1-6 years old with type 1 diabetes.RESEARCH DESIGN AND METHODS -Twenty-six children with type 1 diabetes for Ն6 months were randomly assigned to current therapy (two or three shots per day using NPH insulin and rapid-acting analog) or continuous subcutaneous insulin infusion (CSII) for 6 months. After 6 months, current therapy subjects were offered CSII. Changes in HbA 1c , mean blood glucose (MBG), hypoglycemia frequency, diabetes-related quality of life (QOL), and parental adjustment were recorded.RESULTS -Eleven subjects from each group completed the trial (age 46.3 Ϯ 3.2 months [means Ϯ SE]). At baseline, there were no differences between groups in HbA 1c , MBG, age, sex, diabetes duration, or parental QOL. Mean HbA 1c , MBG, and parental QOL were similar between groups at 6 months. Mean HbA 1c and MBG did not change from baseline to 6 months in either group. The frequency of severe hypoglycemia, ketoacidosis, or hospitalization was similar between groups at any time period. Subjects on CSII had more fasting and predinner mild/ moderate hypoglycemia at 1 and 6 months. Diabetes-related QOL improved in CSII fathers from baseline to 6 months. Psychological distress increased in current therapy mothers from baseline to 6 months. All subjects continued CSII after study completion.CONCLUSIONS -CSII is safe and well tolerated in young children with diabetes and may have positive effects on QOL. CSII did not improve diabetes control when compared with injections, despite more mild/moderate hypoglycemia. The benefits and realistic expectations of CSII should be thoroughly examined before starting this therapy in very young children. Diabetes Care 28:1277-1281, 2005T he Diabetes Control and Complications Trial clearly demonstrated the benefits of good blood glucose control (1,2). However, achieving the necessary good control is not easy and is especially challenging in infants and toddlers with type 1 diabetes. Several factors contribute to the difficulty in managing diabetes in these young children, including unpredictable insulin absorption (3,4), variable eating patterns and activity, increased sensitivity to small amounts of insulin, parental fear of hypoglycemia (5,6), and difficulty in treating hypoglycemia because of their refusal to eat or drink. These problems can lead to widely fluctuating blood glucose levels or frequent hypoglycemia, which could have adverse developmental effects (7,8). Thus, a better way to provide insulin therapy to toddlers and young children with diabetes is desirable.Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) is an attractive way of treating patients with diabetes (9), but there are limited data comparing insulin injection therapy with CSII in toddlers and preschool-aged children with type 1 diabetes (10 -12). Furthermore, although there is an extensive body of literature concerning the complex psychological factors and family management of dia...

Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of L-[3,3-2 H 2 ]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA 1c 6.3 ؎ 0.2, 10.5 ؎ 0.6, and 4.8 ؎ 0.1%, respectively). Glutathione fractional synthesis rate was determined from 2 H 2 -cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P ‫؍‬ 0.009); 2) erythrocyte glutathione concentration was ϳ29% and ϳ36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 ؎ 14 vs. 82 ؎ 11% per day), was substantially higher in the poorly controlled group (141 ؎ 23% per day, P ‫؍‬ 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications. Diabetes

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Blood glutathione concentrations represent a measure of protection against oxidative damage. In earlier studies, we observed that, in adolescents with poorly controlled type 1 diabetes mellitus (T1DM), blood glutathione is significantly depleted because of increased rates of glutathione utilization. To determine whether increased availability of cysteine - one of the three constitutive amino acids of glutathione - would attenuate the alterations in glutathione metabolism, ten 16 +/- 1 yr-old adolescents with poorly controlled T1DM [hemoglobin A1c (HbA1c): 9.9 +/- 1.3%] received 5-h infusions of l-[3,3-(2)H(2)] cysteine and d-[6,6-(2)H(2)]glucose on two occasions, 3 wk apart, after a 10-d oral supplementation with (i) N-acetylcysteine (NAC, 30-45 mg/kg/d) or (ii) L-alanine, in randomized order, and with a 3-wk 'washout' interim period. Blood glucose was maintained in the same hyperglycemic range on both infusion study days, using intravenous insulin. Glutathione fractional synthesis rate (FSR) was determined from (2)H(2)-cysteine incorporation into blood glutathione. NAC supplementation failed to raise erythrocyte cysteine concentrations (23 +/- 6 vs. 17 +/- 1 micromol/L, p = 0.853) and did not alter erythrocyte glutathione concentrations (838 +/- 106 vs. 793 +/- 111 micromol/L, p = 0.220) or glutathione FSR (96 +/- 20 vs. 89 +/- 19%/d, p = 0.974). We conclude that in adolescents with poorly controlled T1DM, dietary cysteine supplementation alone cannot correct glutathione status. In the presence of relative insulinopenia, either higher amino acid doses or aggressive insulin therapy may be needed to achieve this goal. This would require further study.

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