Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVES: Alpha-1 antitrypsin (AAT) has been shown to reduce pro-inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM). METHODS: A 37-wk prospective, open-label, phase I/II interventional trial, comprised of 24 recently diagnosed subjects (12 males; age 12.9 ± 2.4 yr), who received 18 infusions of 40, 60, or 80 mg/kg/dose high-purity, liquid, ready to use AAT over 28 wk (Glassia(®) ; Kamada Ltd., Ness Ziona, Israel). PRIMARY OUTCOMES: safety and tolerability; secondary outcomes: glycemic control, C-peptide reserve, and autoantibody levels. Possible responders were defined as individuals with peak C-peptide that declined less than 7.5% below baseline. RESULTS: No serious adverse events, diabetic ketoacidosis (DKA), or severe hypoglycemic episodes were reported. Adverse events were dose-independent and transient. Glycemic control parameters improved during the study in all groups, independent of dosage. Hemoglobin A1c (HbA1c) decreased from 8.43 to 7.09% (mean, p < 0.001). At the end of the study, 18 subjects (75%) had a peak C-peptide ≥0.2 pmol/mL. Eight subjects (33.3%) were considered possible responders and were characterized by shorter duration of T1DM at screening (54.5 ± 34.3 vs. 95.9 ± 45.7 d, p = 0.036) and greater decrease in their HbA1c during the study period (-2.94 ± 1.55 vs.-0.95 ± 1.83%, p = 0.016). CONCLUSIONS: AAT treatment was safe and well tolerated in pediatric subjects with recently diagnosed autoimmune diabetes. Placebo-controlled studies with larger cohorts and dose range are warranted in order to assess efficacy in maintaining pancreatic beta cell reserve and glycemic control.

Patient perceptions of using the OmniPod system compared with conventional insulin pumps in young adults with type 1 diabetes.

AIMS: This study evaluated treatment satisfaction, comfort, and function using the wireless OmniPod™ Insulin Management System (Insulet Corp., Bedford, MA) compared with conventional (infusion set) insulin pumps in young adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: Twenty-nine patients (age, 24.0 ± 5.1 years; diabetes duration, 12.1 ± 5.7 years; insulin pump duration, 6.4 ± 3.1 years; glycated hemoglobin [HbA1c], 8.6 ± 0.7%) participated in a randomized, two-arm open crossover study comparing two consecutive 12-week periods of continuous subcutaneous insulin infusion (CSII): one period using the OmniPod system and the other period using conventional CSII. The main outcome measures were treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire), user evaluation (OmniPod System User Evaluation Questionnaire), and HbA1c levels. RESULTS: Treatment satisfaction at baseline was high, with a mean score of 28.6±4.6 (maximal score, 36) and no significant difference between the two randomized groups. Upon completion of the study period 43% "would switch to OmniPod," 36% were "undecided," and 21% "would not switch pumps." Seventy-six percent preferred the OmniPod automated cannula insertion system, and 56% reported that OmniPod fit better into their lifestyle than conventional CSII. HbA1c levels significantly decreased with both OmniPod and conventional CSII (7.9 ± 0.9% vs. 8.8 ± 0.7% and 8.2 ± 0.9% vs. 8.5 ± 0.5%, respectively; P<0.001 for both groups) after completion of the first treatment arm. The decrease in HbA1c was more marked in the OmniPod group (P=0.044), without additional improvement at the end of the study in either group. CONCLUSIONS: The OmniPod system was well received by young adults with type 1 diabetes experienced with conventional CSII.

Insulin pump therapy in youth with type 1 diabetes: a retrospective paired study.

OBJECTIVE: To compare by age and glycemic control continuous subcutaneous insulin infusion with multiple daily injections in youth with type 1 diabetes. METHODS: The files of 279 patients who had type 1 diabetes and switched from multiple daily injections to continuous subcutaneous insulin infusion between 1998 and 2003 were reviewed for glycemic control, body mass index standard deviation score, and adverse events. Patients were divided by age as follows: 23 prepubertal (median age: 5.4; range: 1.6-8.6 years), 127 adolescent (median age: 13.7; range 9-17 years), and 129 young adult (median age: 22.8; range: 17-40 years). The data were compared between the 12 months of multiple daily injections that preceded continuous subcutaneous insulin infusion and the period after the start of continuous subcutaneous insulin infusion for the whole cohort and by age group. RESULTS: A significant decrease in hemoglobin A1c was demonstrated after the start of continuous subcutaneous insulin infusion use for the entire cohort (-0.51%) and for the prepubertal (-0.48%), adolescent (-0.26%), and young adult (-0.76%) groups. There was a significant interaction between the change in hemoglobin A1c level and hemoglobin A1c value at initiation of pump therapy (-1.7% for patients with hemoglobin A1c > or = 10%; 0.2% for patients with hemoglobin A1c < or = 7%). The rate of severe hypoglycemic episodes decreased significantly in the adolescent group, from 36.5 to 11.1 events per 100 patient-years, and in the young adult group, from 58.1 to 23.3. There was no significant change in the rate of diabetic ketoacidosis between the 2 periods. The young adults showed a significant decrease in body mass index standard deviation scores (-0.08 +/- 0.37). CONCLUSIONS: Continuous subcutaneous insulin infusion improves glycemic control in youth with type 1 diabetes, especially in those with a history of poor glycemic control. This improvement is associated with a decrease in the rate of severe hypoglycemia in the absence of weight gain.

Exercise with and without an insulin pump among children and adolescents with type 1 diabetes mellitus.

BACKGROUND: The use of insulin pumps is becoming a popular technique for insulin delivery among patients with type 1 diabetes mellitus (T1DM), but there is no consensus regarding the guidelines for proper pump use during exercise. OBJECTIVE: To investigate the physiologic responses and risk of hypoglycemia among children and adolescents with T1DM when exercising with the pump on (PO) (50% of the basal rate) or pump off (PF). METHODS: Ten subjects with T1DM (6 female subjects and 4 male subjects), 10 to 19 years of age, performed prolonged exercise (40-45 minutes) on a cycle ergometer approximately 2 hours after a standard breakfast and an insulin (Lispro) bolus. Complex carbohydrates (20 g) were provided before and after the exercise. Each patient exercised once with PO and once with PF, in a randomized, crossover (single-blind) manner. During exercise and 45 minutes of recovery, subjects were monitored for cardiorespiratory, metabolic, and hormonal responses. Blood glucose concentrations were recorded for 24 hours after exercise, with a continuous glucose monitoring system, to document late hypoglycemic events. RESULTS: During exercise, blood glucose concentrations decreased by 59 +/- 58 mg/dL (mean +/- SD: 29 +/- 24%) with PF and by 74 +/- 51 mg/dL (35.5 +/- 18%) with PO (not significant). No significant differences were found in cortisol, growth hormone, or noradrenaline levels between PO and PF. There were no differences in cardiorespiratory parameters, blood lactate concentrations, or free fatty acids concentrations between pump modes. Hypoglycemic events during exercise were asymptomatic and occurred for 2 subjects with PO and 2 with PF. Nine subjects had late hypoglycemia after PO, compared with 6 after PF (not significant). CONCLUSIONS: We found no advantage for subjects with either PO or PF during exercise, and we noted that late hypoglycemia was more common than hypoglycemia during exercise. However, PO was associated with a trend of increased risk for late hypoglycemia. We recommend that the pump be removed or turned off during prolonged exercise and that blood glucose concentrations be monitored for several hours after exercise, regardless of the pump mode.

Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion.

OBJECTIVE: To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS). DESIGN: Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). SETTING: Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus. INTERVENTIONS: The CGMS was applied for 72 hours after 1 month and at the end of each study arm. MAIN OUTCOME MEASURES: Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm. RESULTS: The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04). CONCLUSIONS: Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.

Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: a randomized open crossover trial.

OBJECTIVE: To compare the efficacy and feasibility of continuous subcutaneous insulin infusion (CSII) with multiple daily insulin injections (MDI) in children with type 1 diabetes. METHODS: The study sample included 23 children (10 males) aged 9.4 to 13.9 years with type 1 diabetes. An open randomized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables: diabetic control, incidence of adverse events, daily insulin requirement, body mass index standard deviation scores, treatment satisfaction, and quality of life. RESULTS: The changes in HbA(1c) and fructoseamine values were similar in the 2 arms over time. At the end of the study, mean HbA(1c) level measured 8.05 +/- 0.78%. There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events. There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI, yielding a rate of 0.26 events per patient-year. There were no episodes of diabetic ketoacidosis. Body mass index standard deviation scores decreased during CSII and increased during MDI, as did mean insulin dose. Patients expressed a higher treatment satisfaction from CSII than MDI, although there was no difference in quality of life between the 2 modes. CONCLUSIONS: Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes, with similar diabetes control and a very low rate of adverse events. We suggest that both modes be available to the diabetic team to better tailor therapy.