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.
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.
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).
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.
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/m2) 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/m2, 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 β‐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.
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.
Intensive and frequent contact with diabetes care providers has been shown to improve glycemic control and reduce risk of complications among T1D pediatric patients. However, remote monitoring ...utilizing newer Bluetooth enabled technology has not been fully evaluated. In a randomized clinical trial, 117 children and adolescents with T1D were assigned to either intensive remote therapy (IRT) or conventional care (CC) for 6 months. Both groups continued routine clinic appointments quarterly and uploaded blood glucose (BG) and device data weekly. Data for patients assigned to IRT were reviewed weekly, and patients were contacted if a regimen adjustment was indicated. The primary outcome of the trial was change in HbA1c from baseline, but the focus of this summary is weekly BG measurements reported from BG meters.In total, 107 subjects (53 in the IRT group) uploaded weekly data. In the first 26 weeks, patients uploaded data an average of 24.7 weeks. The outcomes of interest were summaries of BG measurements, namely average and standard deviation of BG levels and whether measurements were in, below, or above the target range (70-140 mg/dL). Multiple observations per subject were analyzed using generalized linear mixed effects models. Patients in the IRT group had average BG levels 19.3 mg/dL lower than the CC group (P=0.0007). The difference between standard deviations of BG levels was not statistically significant. IRT increased the odds of BG measurements in the target range (OR: 1.25, P=0.0037), as well as the odds of being below the target range (OR: 1.47, P=0.0031), presumably because BG levels were lower. The IRT and CC groups had 24.6% and 20.6% of measurements in the range respectively and 4.7% and 3.2% below the range respectively. These results suggest that IRT can lower BG levels in children and adolescents. Given these promising findings, further research is warranted, as this technology has potential to add convenience and efficiency to T1D management and increase time in target.
Disclosure
L.M. Gandrud: Consultant; Self; UnitedHealth Group. T.L. Barnes: None. D.A. Watson: None.
Regular physical activity (PA) has been found to contribute to lower HbA1c in T1D pediatric populations, but this relationship is not conclusive.
In a recent study, we examined associations between ...PA and HbA1c over 6 months in 1T1D pediatric patients. PA was measured with Fitbit monitors and summarized as average weekly steps and hours of moderate to vigorous PA (MVPA). Linear regression was used to analyze associations and adjust for variables including baseline HbA1c.
Counter to expectations, PA across patients was positively associated with HbA1c. An increase of 10K average steps/week was associated with a 0.115 mmol/mol increase in HbA1c (P=0.017). In addition, an increase of 1 hour of average weekly MVPA was associated with a 0.088 mmol/mol increase in HbA1c (P=0.038). However, within patients, weekly PA levels were negatively associated with weekly BG levels in 75% of patients.
This reversal of trend between within and between patient measures is an interesting example of what is called Simpson’s paradox in statistics. The Figure illustrates how these relationships coexist: weekly data show a negative trend for 3 patients (dashed lines); however, averaged data show a positive trend (solid line).
Although across patients, higher PA tended to be associated with higher HbA1c, the within patient association suggests an encouraging effect in which PA among pediatric patients may actually help to lower HbA1c levels.
Disclosure
D.A. Watson: None. T.L. Barnes: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
Physical activity (PA) in T1D patients has been linked to improved cardiovascular and psychosocial health. Glycemic control has been reported as a benefit of PA, but it remains difficult to assess ...’real-life’ PA in T1D pediatric patients.
In a novel study, we examined the relationship between weekly Fitbit-measured PA and blood glucose (BG) in 1patients over 6 months. BG was measured via home meters. Using generalized linear mixed effects regression we examined the association between weekly PA measures—steps and hours of moderate to vigorous PA (MVPA)—and weekly summaries of BG levels in, below, and above target range (70-140 mg/dL).
On average, patients took 56K steps/week and had a weekly BG measurement of 221 mg/dL. In regression models, as PA increased, patients tended to have significantly lower mean BG levels and more BG measurements in target range. Thus, an increase in 10K steps was associated with a 3.1 mg/dL drop in BG levels and a 6% increase in the odds of a target range BG (see Table). An additional hour of MVPA was associated with a 2.3 mg/dL drop in BG levels and a 4% increase in the odds of a target BG measurement. PA was also associated with being below the target range.Generalized linear mixed effects regression models examining relationship between weekly PA and BG levels1 (n=105)Average BG measurement% BG measurement between 70-140 mg/dL% BG measurement below 70 mg/dL% BG measurement above 140 mg/dLβ (95% CI)2OR (95% CI)3OR (95% CI)3OR (95% CI)3Steps (per 10K)-3.1 (-4.4, -1.8)1.06 (1.05, 1.07)1.06 (1.03, 1.08)0.94 (0.93, 0.95)Hours of MVPA-2.3 (-3.6, -1.0)1.04 (1.03, 1.05)1.03 (1.01, 1.05)0.96 (0.95, 0.97)1 Adjusted for baseline HbA1c, baseline BMI (z-score), age group, sex, treatment group.2 Beta is the fixed effects linear regression coefficient for the specified PA measurement.3 OR is the odds ratio of the indicated event for each unit increase of PA.
This study provides evidence for the positive effects of PA on BG among pediatric T1D patients, providing a further impetus for promoting PA among this population.
Disclosure
T.L. Barnes: None. D.A. Watson: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
Current guidelines from the ADA recommend that children and adolescents with T1D engage in at least 60 minutes of moderate-to-vigorous physical activity (MVPA) every day. However, subjectivity of ...MVPA reporting methods and short study durations compromise the applicability of existing data; there is not a clear picture of MVPA in this population. Therefore, objective measures of MVPA in children and adolescents with T1D are necessary to better understand the importance of other factors related to MVPA like sex, age, and weight.
In a prospective cohort of 1children and adolescents with T1D, physical activity was objectively monitored for 6 months using commercially available activity monitors. Weekly MVPA was summarized as the average number of hours of MVPA for weeks with valid activity monitor use. Regular weekly MVPA in children and adolescents was described by age, sex, and weight. The Mann-Whitney U test was used to assess associations.
In the study population, we observed an average (SD) weekly MVPA of 2.4 (1.7) hours and median (Q1, Q3) weekly MVPA of 1.9 (0.9, 3.0) hours. Sex was significantly associated with MVPA (p<0.0001) with average (SD) weekly MVPA of 3.5 (2.4) hours for males and 1.4 (1.0) hours for females. There was no significant difference in weekly MVPA between children (8-12 years) and adolescents (13-17 years). Interestingly, overweight children (BMI z-score above 85th percentile) were more active than non-overweight children (average weekly MVPA of 3.0 and 2.1 hours respectively), however this difference was not statistically significant.
This study presents data on MVPA in children and adolescents with T1D over a long duration using objectively measured physical activity. Our results suggest that sex is an important factor associated with MVPA and that over 75% of children in this population do not regularly meet the ADA MVPA recommendations.
Disclosure
N.E. Thompson: None. D.A. Watson: None. T.L. Barnes: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
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.
Nineteen children used the Medtronic MiniMed (Northridge, CA) CGMS System Gold on three to seven occasions over approximately 6 months.
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=70 mg/dL) was noted during 28% of 323 nights. When compared to paired meter blood glucose values, the false-positive rate was 16% for mild and 55% for severe sensor hypoglycemia. The mean peak glucose during the 3 h following breakfast (247 +/- 64 mg/dL) was higher than following lunch (199 +/- 67 mg/dL) or dinner (194 +/- 63 mg/dL). The rate of glucose rise to peak was >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.
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.
Objective: To compare measured HbA1c, estimated HbA1c, and percent time in range before and after the initiation of the Minimed 670G system in children and young adults with type 1 diabetes (T1D).
...Methods: Data consisted of 67 T1D patients, aged 5-23 years, who started the MiniMed 670G system and were followed for at least 12 weeks. Data were analyzed at baseline and 2, 4, 8, and 12 weeks following Auto Mode start. Paired t tests and linear mixed regression models were used to evaluate the effect of time on percent of time in Auto Mode, percent of time in range (70-180 mg/L) and changes in most recently measured HbA1c and sensor estimated HbA1c.
Results: Fifteen percent of patients (n=10) were aged 5-9 years, 27% (n=18) were 10-13 years, 30% (n=20) were 14-17 years and 28% (n=19) were ≥ 18 years; average duration of T1D was 5.47 ± 4.26 years. Nearly 96% of patients were Caucasian; 54% were male. Estimated HbA1c levels decreased from 8.10% ± 1.26% at baseline to 7.51% ± 0.88% at 12 weeks (P<0.0001). Measured HbA1c decreased from 7.98% ± 1.03% to 7.73% ± 1.03% (P=0.0008) (Figure 1). Percent time in range increased from 50% at baseline to 61% at 12 weeks (P<0.0001), without significant change in time below range. Time in Auto Mode declined from 75.1% at start to 68.4% at 12 weeks (P=0.0015).
Conclusion: Initiation of the 670G system in a clinical setting led to improved glycemic control in children, adolescents, and young adults.
Disclosure
C.J. Henson: None. T.L. Barnes: None. A.J. Nickel: None. M. Abuzzahab: Research Support; Self; Ascendis, Genentech, Inc., Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc.. Research Support; Self; Versartis, Inc., Medtronic. Advisory Panel; Self; Sandoz. J. Kyllo: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
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.
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