Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

INTRODUCTION: GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Stakeholder Engagement in Type 1 Diabetes Research, Quality Improvement, and Clinical Care.

The integration of stakeholder engagement (SE) in research, quality improvement (QI), and clinical care has gained significant traction. Type 1 diabetes is a chronic disease that requires complex daily management and care from a multidisciplinary team across the lifespan. Inclusion of key stakeholder voices, including patients, caregivers, health care providers and community advocates, in the research process and implementation of clinical care is critical to ensure representation of perspectives that match the values and goals of the patient population. This review describes the current framework for SE and its application to research, QI, and clinical care across the lifespan.

Impacts of the COVID-19 pandemic on the diagnosis of idiopathic central precocious puberty in pediatric females in New York City.

OBJECTIVES: The COVID-19 pandemic had profound effect on physical and mental health. Stress was due physical inactivity, increased screen time, social isolation, fear of illness/death, as well as relative lack of resources including healthy food and finances. These stressors may be associated with an increase in idiopathic central precocious puberty (ICPP). The aim of the study was to assess the incidence of ICPP in females during the COVID-19 pandemic and compare biochemical and radiological parameters of females diagnosed in the previous two years, looking at associations among BMI, screen time, isolation, and stress in relation to the development of early puberty. METHODS: A retrospective chart review was performed of females diagnosed with ICPP. We divided subjects into a pandemic group and pre-pandemic group based on time of diagnosis. We compared anthropometric, serologic and radiologic data between the two groups. To assess psychosocial stress, we reviewed a COVID-19 impact survey which was administered to families at our endocrine clinic. RESULTS: There were a total of 56 subjects in the study; 23 subjects in the pre-pandemic group and 33 in the pandemic group. The pandemic cohort had significantly higher estradiol and LH levels and larger ovarian volumes. Survey results showed parental report of stress was moderate in 38 % of subjects and severe in 25 % of parents. In children, reported stress was moderate in 46 % of subjects. CONCLUSIONS: As puberty is influenced by exogenous factors including weight gain and psychosocial stress, we suspect that the environmental stress surrounding the pandemic influenced the increase in ICPP.

Time, Technology, Social Support, and Cardiovascular Health of Emerging Adults With Type 1 Diabetes.

BACKGROUND: Emerging adults with Type 1 diabetes (T1DM) face an increased risk of cardiovascular disease; however, there are both barriers and facilitators to achieving ideal cardiovascular health in this stage of their lives. OBJECTIVES: The aim of this study was to qualitatively explore the barriers and facilitators of achieving ideal levels of cardiovascular health in a sample of emerging adults with T1DM ages 18-26 years. METHODS: A sequential mixed-methods design was used to explore achievement of ideal cardiovascular health using the seven factors defined by the American Heart Association (smoking status, body mass index, physical activity, healthy diet, total cholesterol, blood pressure, and hemoglobin A1C [substituted for fasting blood glucose]). We assessed the frequency of achieving ideal levels of each cardiovascular health factor. Using Pender's health promotion model as a framework, qualitative interviews explored the barriers and facilitators of achieving ideal levels of each factor of cardiovascular health. RESULTS: The sample was mostly female. Their age range was 18-26 years, with a diabetes duration between 1 and 20 years. The three factors that had the lowest achievement were a healthy diet, physical activity at recommended levels, and hemoglobin A1C of <7%. Participants described lack of time as a barrier to eating healthy, being physically active, and maintaining in-range blood glucose levels. Facilitators included the use of technology in helping to achieve in-range blood glucose and social support from family, friends, and healthcare providers in maintaining several healthy habits. DISCUSSION: These qualitative data provide insight into how emerging adults attempt to manage their T1DM and cardiovascular health. Healthcare providers have an important role in supporting these patients in establishing ideal cardiovascular health at an early age.

Exercise and Self-Management in Adults with Type 1 Diabetes.

PURPOSE OF REVIEW: The purpose of this review paper is to examine the most recent evidence of exercise-related self-management in adults with type 1 diabetes (T1D). RECENT FINDINGS: This paper reviews the benefits and barriers to exercise, diabetes self-management education, the role of the healthcare provider in assessment and counseling, the use of technology, and concerns for special populations with T1D. Adults with T1D may not exercise at sufficient levels. Assessing current levels of exercise, counseling during a clinical visit, and the use of technology may improve exercise in this population.

Cardiovascular health in emerging adults with type 1 diabetes.

AIMS: Individuals with type 1 diabetes (T1D) face increased risk for cardiovascular disease (CVD). Controlling individual cardiovascular risk factors can prevent or slow the onset of CVD. Ideal cardiovascular health is associated with a lower incidence of CVD. Identifying areas of suboptimal cardiovascular health can help guide CVD prevention interventions. To assess cardiovascular health and explore the barriers and facilitators to achieving ideal cardiovascular health in a sample of young adults with T1D. METHODS AND RESULTS: We used a sequential mixed-method design to assess the seven factors of cardiovascular health according to American Heart Association. Qualitative interviews, guided by Pender's Health Promotion Model, were used to discuss participant's cardiovascular health results and the barriers and facilitators to achieving ideal cardiovascular health. We assessed the frequency of ideal levels of each factor. The qualitative data were analysed using content analysis. Qualitative and quantitative data were integrated in the final analysis phase. The sample (n = 50) was majority female (70%), White (86%), with a mean age of 22 ± 2.4 and diabetes duration of 10.7 ± 5.5 years. Achievement of the seven factors of cardiovascular health were: non-smoking (96%); cholesterol <200 mg/dL (76%); body mass index <25 kg/m2 (54%); blood pressure <120/<80 mmHg (46%); meeting physical activity guidelines (38%); haemoglobin A1c <7% (40%); and healthy diet (14%). Emerging qualitative themes related to the perceived benefits of action, interpersonal influences on their diabetes self-management, and perceived self-efficacy. CONCLUSION: We found areas of needed improvement for cardiovascular health. However, these young adults expressed a strong interest in healthy habits which can be supported by their healthcare providers.

Pediatric Smart Insulin Pen Use: The Next Best Thing.

In the pediatric population, insulin pump therapy, or CSII, is often considered the gold standard for intensive diabetes management. Insulin pump technology offers families and caregivers many beneficial features including a calculator for insulin dosing and the ability to review diabetes management data to provide data-driven diabetes management. However, for those who find CSII challenging or choose to use multiple daily injections (MDI) there is an option that offers similar features called the Smart Insulin Pen (SIP). Even though SIP technology provides a safe and data-driven diabetes self-management tool for the pediatric population using MDI, there is limited pediatric specific literature. This article will describe current options, data-driven diabetes management, benefits, challenges and clinical use of SIP technology in the pediatric population.

Perspectives on the role of exercise in the treatment of pediatric type 1 diabetes.

BACKGROUND: Studies demonstrate that children with type 1 diabetes may not be meeting exercise recommendations. This, coupled with the lack of data on the determinants of exercise promotion in youth, may indicate a need for additional focus on exercise guidelines and promotion in youth with type 1 diabetes. OBJECTIVE: The objective of this study is to understand provider perspectives regarding exercise promotion in children with type 1 diabetes. SUBJECTS AND METHODS: An online survey regarding perspectives on exercise was emailed to Pediatric Endocrine Society members. RESULTS: Of the 84 respondents, 85.5% believe counseling regarding exercise recommendations is a priority. However, 87.8% did not identify Office of Disease Prevention and Health Promotion (ODPHP) guidelines correctly and 79.3% did not identify American Diabetes Association (ADA) guidelines correctly. Providers who exercised regularly (P = .009) and providers who identified ODPHP guidelines correctly (P = .004) were more likely to identify ADA guidelines correctly. Providers who identified ADA guidelines correctly were 4.21 times (OR 4.21; 95% CI 1.30-13.7) more likely to make good recommendations and those who discussed recommendations at diagnosis were 6.10 times (OR 6.10; 95% CI 1.76-21.2) more likely to make good recommendations. CONCLUSION: To our knowledge, this study is the first to investigate provider perspectives of exercise promotion in children with type 1 diabetes. We found provider recommendations were not consistent with ADA exercise guidelines and most providers were not fully aware of the recommendations. Future research should address increasing provider education regarding exercise guidelines and developing exercise promotion tools.

Use of Sitagliptin With Closed-Loop Technology to Decrease Postprandial Blood Glucose in Type 1 Diabetes.

BACKGROUND: Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system. METHODS: This was a randomized, double-blinded, placebo controlled, crossover design trial. The participants were18-35 years old, had T1DM, and an HbA1c of ≤ 8.5%. A dose determination study included eight subjects with T1DM. There were three study visits. Four hours after receiving study drug (placebo, sitagliptin 50 mg, sitagliptin 100 mg), subjects underwent a mixed meal tolerance test with assessment of hormone concentrations. In a second study, 15 subjects underwent two visits receiving either placebo or 100 mg of sitagliptin plus an insulin only closed-loop system for 25 hours with timed meals. Blood glucose and other hormone concentrations were analyzed using repeated measures ANOVA. RESULTS: For the dose determination study, sitagliptin 100 mg resulted in reduced postprandial blood glucose ( P = .006). For the closed-loop study, glucose concentrations were lower in the treatment group, most prominently during the first two study meals ( P = .03). There was no difference in glucagon concentrations, but insulin concentrations and insulin delivery were lower in the treatment group. CONCLUSIONS: Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.

Pediatric Type 1 Diabetes: Reducing Admission Rates for Diabetes Ketoacidosis.

BACKGROUND: Diabetes ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Reducing DKA admissions in children with T1DM requires a coordinated, comprehensive management plan. We aimed to decrease DKA admissions, 30-day readmissions, and length of stay (LOS) for DKA admissions. METHODS: A multipronged intervention was designed in 2011 to reach all patients: (1) increase insulin pump use and basal-bolus regimen versus sliding scales, (2) transform educational program, (3) increased access to medical providers, and (4) support for patients and families. A before-after study was conducted comparing performance outcomes in years 2007-2010 (preintervention) to 2012-2014 (postintervention) using administrative data and Wilcoxon rank sum and Fischer exact tests. RESULTS: DKA admissions decreased by 44% postintervention (16.7 vs 9.3 per 100 followed patient-years; P = .006), unique patient 30-day readmissions decreased from 20% to 5% postintervention (P = .001), and median LOS significantly decreased postintervention (P < .0001). Although not an original goal of the study, median hemoglobin A1C of a subset of the population transitioned from sliding scale decreased, 10.3% to 8.9% (P < .02). CONCLUSIONS: When clinical and widespread program interventions were used, significant reductions in DKA hospitalizations, 30-day readmissions, and LOS occurred for pediatric T1DM. Continuous performance improvement efforts are needed for improving DKA outcomes.

Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes: A Randomized Open-Labeled Crossover Design Trial.

BACKGROUND: The closed-loop (CL) system delivers insulin in a glucose-responsive manner and optimal postprandial glycemic control is difficult to achieve with the algorithm and insulin available. We hypothesized that adjunctive therapy with liraglutide, a once-daily glucagon-like peptide-1 agonist, would be more effective in normalizing postprandial hyperglycemia versus insulin monotherapy in the CL system, in patients with type 1 diabetes. METHODS: This was a randomized, controlled, open-label, crossover design trial comparing insulin monotherapy versus adjuvant subcutaneous liraglutide 1.2 mg and insulin, using the CL system in 15 patients. Blood glucose (BG), insulin, and glucagon concentrations were analyzed. RESULTS: The liraglutide arm was associated with overall decreased mean BG levels (P = .0002). The average BG levels from 8:00 pm (day 1) to 9:00 pm (day 2) were lower in the liraglutide arm (144.6 ± 36.31 vs 159.7 ± 50.88 mg/dl respectively; P = .0002). Two-hour postbreakfast and lunch BG profiles were better in the liraglutide arm (P < .05) and the insulin and glucagon assay values were lower (P < .0001). Postprandially, the area under the curve (AUC) for 2-hour postbreakfast and lunch BG levels were significant (P = .01, P = .03) and the AUC for glucagon, postbreakfast (P < .0001) and lunch (P < .05), was also significant. The incidence of hypoglycemia did not differ between arms (P = .83, Fisher's exact test). Overall, adjunct liraglutide therapy plus CL was well tolerated even with expected side effects. CONCLUSION: This is a proof-of-concept study showing liraglutide can be a potential adjunctive therapy in addition to CL with insulin to reduce postprandial hyperglycemia in type 1 diabetes.

Evaluating emergency preparedness and impact of a hurricane sandy in pediatric patients with diabetes.

BACKGROUND: Natural disasters have always been associated with significant adverse events including medical and mental health problems. Children with chronic disease such has diabetes have also been believed to be affected to a greater extent by any natural disaster. The purpose of this study was to assess and compare emergency preparedness post-disaster and post-traumatic stress effects of Hurricane Sandy in affected and relatively unaffected populations. METHODS: The study was conducted between February and July 2013. A total of 142 families caring for children with Type 1 Diabetes Mellitus (T1DM) who attended clinics were recruited from hospitals in Bronx, NY (control) and in NJ (affected) by Hurricane Sandy. Subjects were recruited to participate in a survey 3-6 months after the hurricane. Data on demographics, glycemic control and insulin regimens were collected. Families were surveyed for socio-economic status (SES), using Hollingshead questionnaire, general and diabetes preparedness and the Hurricane Related Traumatic Experiences (HURTE) questionnaire was used to evaluate for symptoms of post-traumatic stress. RESULTS: Ninety-five percent of families reported to be generally well to moderately prepared for the hurricane and 83 % reported to be very well prepared with regards to their child's diabetes during the disaster. There was no difference between the sites for preparedness for the disaster, age or gender. There was a trend toward significance (p < 0.06) in New Jersey subjects as to a greater psychological impact from the hurricane. Poor glycemic control was significantly associated with lower SES (p < 0.008). Most importantly, SES was unrelated to preparedness for diabetes management during the hurricane. CONCLUSIONS: Despite low SES, families were generally well to moderately prepared for hurricane. In children with diabetes, interventional studies should be designed and implemented so that glycemic control remains unaffected, following any major disaster.