Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.

OBJECTIVE: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population. RESEARCH DESIGN AND METHODS: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy. RESULTS: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204). CONCLUSIONS: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.

Short-Term PTH(1-34) Therapy in Children to Correct Severe Hypocalcemia and Hyperphosphatemia due to Hypoparathyroidism: Two Case Studies.

The standard treatment of hypoparathyroidism is to control hypocalcemia using calcitriol and calcium supplementation. However, in severe cases this approach is insufficient, and the risks of intravenous (i.v.) calcium administration and prolonged hospitalization must be considered. While the use of recombinant human parathyroid hormone 1-34 [rhPTH(1-34)] for long-term control of hypocalcemia has been established, the benefits of short-term rhPTH(1-34) treatment in children have not been explored. We report two patients with hypoparathyroidism treated with rhPTH(1-34). Patient 1 is a 10-year-old female with polyglandular autoimmune syndrome type 1. Patient 2 is a 12-year-old female with hypoparathyroidism after total thyroidectomy. Both patients showed poor response to i.v. and oral calcium and calcitriol, and patient 1 did not respond to phosphate binders. Patient 1 had rapid increase in serum calcium with a decrease in serum phosphate after a 3-day course of subcutaneous rhPTH(1-34). Patient 2 had normalization of calcium and phosphate levels after a 7-day course of rhPTH(1-34). These cases support a role for rhPTH(1-34) in the acute management of hypoparathyroidism in hospitalized patients to more rapidly correct hypocalcemia and hyperphosphatemia, shorten hospitalization, and reduce the need for frequent i.v. calcium boluses.

Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial.

OBJECTIVE: To assess the safety and efficacy of short-term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity. METHODS: Adolescents (ages 12-18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2 ) were recruited for this double-blind, randomized, placebo-controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups. RESULTS: Thirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2 ) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (-1.9%; 95% CI: -5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very-low-density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health. CONCLUSIONS: In this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low-dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.

Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study.

The objective of this pilot study was to evaluate the effects of exenatide on BMI (primary endpoint) and cardiometabolic risk factors in nondiabetic youth with extreme obesity. Twelve children and adolescents (age 9-16 years old) with extreme obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m(2)) were enrolled in a 6-month, randomized, open-label, crossover, clinical trial consisting of two, 3-month phases: (i) a control phase of lifestyle modification and (ii) a drug phase of lifestyle modification plus exenatide. Participants were equally randomized to phase-order (i.e., starting with control or drug therapy) then crossed-over to the other treatment. BMI, body fat percentage, blood pressure, lipids, oral glucose tolerance tests (OGTT), adipokines, plasma biomarkers of endothelial activation, and endothelial function were assessed at baseline, 3-, and 6-months. The mean change over each 3-month phase was compared between treatments. Compared to control, exenatide significantly reduced BMI (-1.7 kg/m(2), 95% confidence interval (CI) (-3.0, -0.4), P = 0.01), body weight (-3.9 kg, 95% CI (-7.11, -0.69), P = 0.02), and fasting insulin (-7.5 mU/l, 95% CI (-13.71, -1.37), P = 0.02). Significant improvements were observed for OGTT-derived insulin sensitivity (P = 0.02) and ß-cell function (P = 0.03). Compliance with the injection regimen was excellent (≥94%) and exenatide was generally well-tolerated (the most common adverse event was mild nausea in 36%). These preliminary data suggest that exenatide should be evaluated in larger, well-controlled trials for its ability to reduce BMI and improve cardiometabolic risk factors in youth with extreme obesity.