OBJECTIVE: To gather preliminary data on the feasibility and efficacy of etanercept therapy to prolong endogenous insulin production in pediatric patients with newly diagnosed type 1 diabetes.RESEARCH DESIGN AND METHODS: This was a 24-week double-blind, randomized, placebo-controlled study conducted at the Diabetes Center, Women and Children's Hospital of Buffalo. Eighteen subjects (11 male and 7 female, aged 7.8–18.2 years) were randomly assigned to receive either placebo or etanercept. Inclusion criteria included age 3–18 years, GAD-65 and/or islet cell antibody positivity, A1C >6%, three insulin injections per day, white blood cell count 3,000–10,000, platelets >100,000, and normal liver and renal function. Intention-to-treat analysis was used.RESULTS: A1C at week 24 was lower in the etanercept group (5.91 ± 0.5%) compared with that in the placebo group (6.98 ± 1.2%; P < 0.05) with a higher percent decrease from baseline than in the placebo group (etanercept 0.41 ± 0.1 vs. placebo 0.18 ± 0.21; P < 0.01). The percent change in C-peptide area under the curve from baseline to week 24 showed a 39% increase in the etanercept group and a 20% decrease in the placebo group (P < 0.05). From baseline to week 24 insulin dose decreased 18% in the etanercept group compared with a 23% increase in the placebo group (P < 0.05). Seventeen patients completed the study, and none withdrew because of adverse events.CONCLUSIONS: In this small pilot study, treatment of pediatric patients newly diagnosed with type 1 diabetes with etanercept resulted in lower A1C and increased endogenous insulin production, suggesting preservation of β-cell function. A larger study is needed to further explore safety and efficacy.

OBJECTIVE—The aim of this study was to determine whether premeal pulmonary delivery of rapid-acting, dry-powder insulin (Exubera) plus Ultralente could provide glycemic control comparable to a conventional insulin regimen in type 1 diabetes. RESEARCH DESIGN AND METHODS—Three hundred thirty-five subjects were randomly assigned to receive either premeal inhaled insulin plus bedtime Ultralente or two to three injections of regular and NPH insulin for 24 weeks. The primary end point was a change in HbA_1c. RESULTS—Mean decreases in HbA_1c values were comparable for inhaled (8.1–7.9%) and conventional groups (8.1–7.7%) (adjusted treatment group difference 0.16% [95% CI −0.01 to 0.32]). There were greater reductions for inhaled versus conventional regimen in fasting and postprandial plasma glucose (adjusted mean change differences −25.17 and −30.28 mg/dl, respectively [95% CI −43.39 to −6.95 and −54.58 to −5.97, respectively]). Hypoglycemia (events/subject month) was lower for the inhaled (8.6) versus the conventional (9.0) group (risk ratio, 0.96 [95% CI 0.93–0.99]). In subjects receiving inhaled insulin, increased insulin antibody levels were observed, but there were no associated clinical or laboratory changes. Adverse events were comparable between groups. Mild to moderate cough was more frequent in the inhaled insulin group (27 vs. 5%) but decreased during the treatment. Pulmonary function tests were not different between the groups except for a greater decrease in carbon monoxide diffusing capacity in the inhaled insulin group. Treatment satisfaction was greater in the inhaled than in the conventional group. CONCLUSIONS—Inhaled insulin is effective, well tolerated, and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen.

OBJECTIVE: To test the efficacy of an innovative family-based intervention for overweight preschool-aged children and overweight parents conducted in the primary care setting. METHODS: Children with BMI ≥85th percentile and an overweight parent were randomized to intervention or information control (IC). Trained staff delivered dietary and physical/sedentary activities education to parents over 6 months (10 group meetings and 8 calls). Parents in the intervention received also behavioral modification. An intention-to-treat analysis was performed by using mixed analysis of variance models to test changes in child percent over BMI (%OBMI) and z-BMI and to explore potential moderators of group differences in treatment response. RESULTS: Ninety-six of 105 randomized families started the program: 46 children (31 girls/15 boys) in the intervention and 50 (33 girls/17 boys) in the IC, with 33 and 39 mothers and 13 and 11 fathers in intervention and IC, respectively. Baseline characteristics did not differ between groups. Children in the intervention group had greater %OBMI and z-BMI decreases at 3 and 6 months compared with those assigned to IC (P < .0021). A greater BMI reduction over time was also observed in parents in the intervention compared with parents assigned to IC (P < .0001). Child %OBMI and parent BMI changes were correlated (r = .31; P = .003). Children with greater baseline %OBMI were more likely to have a greater %OBMI decrease over time (P = .02). CONCLUSIONS: Concurrently targeting preschool-aged overweight youth and their overweight parents for behavioral weight control in a primary care setting reduced child %OBMI and parent BMI, with parent and child weight changes correlating.

Objective. The objective of this study was to characterize a population of obese children who were referred to a pediatric endocrinology clinic and to analyze the outcome of the referral.

OBJECTIVE: The T1GER (A Study of SIMPONI to Arrest β-Cell Loss in Type 1 Diabetes) study showed many metabolic benefits of the tumor necrosis factor-α blocker golimumab in children and young adults with type 1 diabetes (T1D). Off-therapy effects are reported.RESEARCH DESIGNS AND METHODS: T1GER was a phase 2, placebo-controlled, randomized trial in which golimumab or placebo was administered for 52 weeks to participants 6–21 years old diagnosed with T1D within 100 days of randomization. Assessments occurred during the 52-week on-therapy and 52-week off-therapy periods.RESULTS: After treatment was stopped, C-peptide area under the curve (AUC) remained greater in the treatment versus control group. At weeks 78 and 104, the golimumab group had lower reductions in the 4-h C-peptide AUC baseline than the placebo group, where specifically the golimumab group had reductions of 0.31 and 0.41 nmol/L, and the placebo group had reductions of 0.64 and 0.74 nmol/L. There were also trends in less insulin use, higher peak C-peptide levels and those in partial remission, and higher peak C-peptide levels in the golimumab group. Golimumab responders, defined as having an increase or minimal loss of C-peptide AUC and/or being in partial remission at week 52, showed even greater improvements in most metabolic parameters on and off therapy and had less hypoglycemia during the off-therapy period versus placebo. Adverse events, including infections, were similar between the groups during all time periods of the study.CONCLUSIONS: In children and young adults with new-onset T1D, golimumab preserved endogenous β-cell function and resulted in other favorable metabolic parameters on and off therapy. A subpopulation had disease stabilization while on therapy, with improved metabolic parameters off therapy.