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.

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.

The Medtronic Minimed Gold continuous glucose monitoring system: an effective means to discover hypo- and hyperglycemia in children under 7 years of age.

BACKGROUND: The glycemic patterns of children less than 7 years with type 1 diabetes have not been well studied using continuous glucose monitoring. Our goal was to assess the incidence of hypoglycemia as well as postprandial glycemic patterns in this age group utilizing continuous glucose monitoring. METHODS: Nineteen children used the Medtronic MiniMed (Northridge, CA) CGMS System Gold on three to seven occasions over approximately 6 months. RESULTS: Nineteen children (nine girls and 10 boys; mean age 4.8 +/- 1.4 years, range 1.6-6.8 years) used the CGMS 102 times, providing 434 days of data; 79% of days were optimal based on CGMS Solutions software version 3.0. Mild hypoglycemia (glucose or=2 mg/dL/min following 50% of breakfasts. Children with hemoglobin A1c levels >or=8% had higher postprandial glucose concentrations. There was no significant advantage of continuous subcutaneous insulin infusion therapy over multiple daily injection therapy in decreasing postprandial hyperglycemia. CONCLUSIONS: CGMS tracings from young children with diabetes demonstrate frequent mild nocturnal hypoglycemia and significant postprandial hyperglycemia, with a rapid rise in glucose following the meal. The most rapid rate of rise and the most severe postprandial hyperglycemia occurred after breakfast.

Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty.

BACKGROUND: Dosing of monthly depot leuprolide (DL) in central precocious puberty (CPP) varies considerably. U.S. practitioners use 7.5-15 mg, in contrast with the international standard of 3.75 mg. Pubertal suppression using the newer 3-month DL also has been reported from Europe. To date there have been no direct comparisons of these different DL doses. OBJECTIVES: In an open 12-month protocol, we tested the efficacy of three DL doses (7.5 mg- and 3.75 mg-1 month and 11.25 mg-3 month) given sequentially to subjects treated for CPP. Primary outcome measures were stimulated gonadotropin (Gn) levels at 12-wk intervals. The null hypothesis was no difference among doses. METHODS: Both existing and new patients with CPP received our standard therapy (DL 7.5 mg every 4 wk) for a minimum of 24 wk. In subjects with DL-stimulated LH 2 IU/liter or less, the dose was changed to 3.75 mg every 4 wk and evaluated 12 wk later. Subjects who met LH criteria (<4.5 IU/liter) on 3.75 mg then received a single dose of 11.25 mg-3 month and were reevaluated 12 wk later. Serum LH/FSH and sex steroids were obtained 40 min after DL injection. RESULTS: Thirty subjects were enrolled (20 naive; 24 girls, 6 boys), and 21 were evaluated on all three DL doses. DL-stimulated LH levels (mean +/- sd) were 1.30 +/- 0.74, 1.73 +/- 0.99, and 2.13 +/- 1.41 on 7.5 mg, 3.75 mg, and 11.25 mg-3 month, respectively (7.5 vs. 3.75 mg, P = 0.019; 7.5 mg vs. 11.25 mg-3 month, P = 0.004, Wilcoxon ranked sign test). Mean FSH levels were 2.86 +/- 1.91, 3.91 +/- 1.98, and 3.96 +/- 1.34, respectively (7.5 vs. 3.75 mg, P = 0.017; 7.5 mg vs. 11.25 mg-3 month, P = 0.020). No differences were detected in mean sex steroid levels. CONCLUSIONS: Stimulated LH and FSH levels were significantly higher during therapy with both the 3.75 mg and 11.25 mg-3 month depot leuprolide doses, compared with 7.5 mg, contradicting the null hypothesis of no difference. These data suggest that low-dose 1- and 3-month DL preparations are associated with persistently greater gonadal stimulation in most CPP patients, but the LH/FSH results were not corroborated by differences in sex steroid levels. Whether various DL doses lead to long-term therapeutic differences remains to be determined.

Is growth hormone stimulation testing in children still appropriate?

The diagnosis of growth hormone deficiency (GHD) historically has relied on measurement of growth hormone (GH) concentrations following stimulation, usually with a non-physiologic provocative agent. Despite the use of more specific GH assays, the peak concentration of GH below which a child is considered GH deficient has risen. We examine the pitfalls associated with GH stimulation tests, specifically, the lack of reliability and accuracy of these tests, and their inability to predict who will benefit from GH therapy. We recommend that GH stimulation tests no longer routinely be used for the diagnosis of GHD in children.

Use of the Cygnus GlucoWatch biographer at a diabetes camp.

BACKGROUND: Detection and prevention of nocturnal hypoglycemia is a major medical concern at diabetes camps. OBJECTIVE: We conducted an open-label trial of the Cygnus GlucoWatch biographer to detect nocturnal hypoglycemia in a diabetes camp, a nonclinical environment with multiple activities. METHODS: Forty-five campers (7-17 years old) wore a biographer. The biographer was placed on the arm at 6:00 PM, with the low alarm set to 85 mg/dL (4.7 mmol/L). Overnight glucose monitoring occurred per usual camp protocol. Counselors were to check and record blood glucose values if the biographer alarmed. RESULTS: Biographers were worn for 154 nights by 45 campers. After a 3-hour warm-up period, 67% of biographers were calibrated, of which 28% were worn the entire night (12 hours). Thirty-four percent of readings were skipped because of: "data errors" (65%), sweat (20%), and temperature change (16%). Reported biographer values correlated with meter glucose values measured 11 to 20 minutes later (r = 0.90). Of 20 low-glucose alarms with corresponding meter values measured within 20 minutes, there were 10 true-positive alarms, 10 false-positive alarms, and no false-negative alarms. Campers reported sleep disruption 32% of the nights, and 74% found the biographer helpful. Campers reported they would wear the biographer 4 to 5 nights each week. CONCLUSIONS: Half of the biographer low-glucose alarms that had corresponding blood meter values were true-positive alarms, and the remaining were false-positive alarms. There was close correlation between the biographer and meter glucose values. The majority of campers found the biographer helpful and would use it at home.

Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis.

Despite the proven efficacy of low-dose pamidronate in adults with osteoporosis, the efficacy of the low-dose regimen in children has not been studied. Pamidronate (1 mg/kg) was administered intravenously once every 3 months to 11 children with osteoporosis. Treatment was associated with reduced fracture rates and increased areal (BMD) and volumetric (BMAD) bone mineral density measured by dual energy X-ray absorptiometry (DXA). The mean annualized percent gain was 20.1 +/- 16.9 (4.7 to 59.1, n = 9) for spinal BMD and 15.1 +/- 18.1 (-11.0 to 40.2, n = 9) for spinal BMAD. Common adverse effects including fever, muscle aches, nausea and fatigue were self-limited and generally occurred only after the first infusion. Clinically significant hypocalcemia did not occur. Low-dose pamidronate appears promising in the treatment of childhood osteoporosis.