Diazoxide, the only U.S. Food and Drug Administration-approved drug to treat hyperinsulinemic hypoglycemia, has been associated with several adverse events, which has raised concerns about the safety ...of this drug. Existing reports are limited to small studies and case reports.
To determine prevalence of and clinical factors associated with adverse events in infants and children treated with diazoxide.
Retrospective cohort study of children with hyperinsulinism (HI) treated with diazoxide between 2003 and 2014.
The Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia.
Children and infants with laboratory-confirmed diagnosis of HI.
Prevalence of pulmonary hypertension (PH), edema, neutropenia, thrombocytopenia, and hyperuricemia was determined. Tests of association and logistic regression were used to identify potential risk factors.
A total of 295 patients (129 female) met inclusion criteria. The median age at diazoxide initiation was 29 days (interquartile range, 10 to 142 days; n = 226 available start dates); 2.4% of patients were diagnosed with PH after diazoxide initiation. Children with PH (P = 0.003) or edema (P = 0.002) were born at earlier gestational age and more frequently had potential PH risk factors, including respiratory failure and structural heart disease (P < 0.0001 and P = 0.005). Other adverse events included neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%).
In this large cohort, PH occurred in infants with underlying risk factors, but no identifiable risk profile emerged for other adverse events. The relatively high prevalence of neutropenia, thrombocytopenia, and hyperuricemia suggests the value in proactively screening for these side effects in children treated with diazoxide.
Background: Adolescents with T2D engage in little moderate-to-vigorous PA. Although autonomous (internally driven) motivation is associated with PA engagement in healthy individuals, whether this is ...true for AYA with T2D or prediabetes is unknown.
Methods: Participants were 13-22 years old with T2D or prediabetes who were enrolled in an ongoing trial (NCT04874415) to promote PA. Prior to randomization, we assessed autonomous motivation to exercise (Relative Autonomy Index, RAI) using the Behavioral Regulation to Exercise Questionnaire-3. To assess PA, AYA completed PACE+ survey (days active <60 min in last and typical weeks) and used a wrist-worn activity tracker for 14 days. Associations between RAI and PA were assessed using Pearson correlation and linear regression.
Results: Participants (n=33; 19F; 19 T2D, 14 prediabetes) were 15.9 ± 2.0 years and racially diverse (57% non-White). Correlation between RAI and step count was strong (r=0.5, p=0.001), and the highest RAI quartiles achieved <3000 more steps/day than the lowest (p<0.05). RAI also correlated with PACE+ days active/week (r=0.4, p=0.01). Relationships persisted after adjustment for age, sex, race, and T2D.
Conclusion: Greater autonomous motivation to exercise was associated with higher objective and subjective PA. Autonomous motivation may be a target for behavioral intervention in AYA with T2D or prediabetes.
Disclosure
M.Vajravelu: None. A.Rodriguez gonzalez: None. B.Hewitt: None. A.Kriska: None. J.Mitchell: None. V.Helgeson: None. S.Amaral: Advisory Panel; Bristol-Myers Squibb Company. S.A.Arslanian: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Consultant; Société des Produits Nestlé SA,, Other Relationship; Eli Lilly and Company, AstraZeneca, Research Support; Novo Nordisk, Eli Lilly and Company.
Funding
National Institutes of Health (K23DK125719, UL1TR001857)
Objective: Youth-onset type 2 diabetes, most common among racial/ethnic minorities, threatens to widen health disparities due to severe complications in early adulthood and a 15-year reduction in ...life expectancy. Use of continuous glucose monitors (CGM) improves diabetes management in adults with type 2 diabetes, but socioeconomic and racial/ethnic disparities in diabetes technology use remain. We sought to examine factors impacting the acceptability of CGM use in adolescents and young adults (AYA) with type 2 diabetes.
Methods: In this single center study, we conducted semi-structured interviews with AYA with type 2 diabetes and their parents to determine attitudes about CGM use, including barriers and facilitators. Interviews were audio-recorded, transcribed, and evaluated using thematic analysis.
Results: Twenty AYA and 10 parents participated (n=30 total). AYA were mean age 16.5 years (SD 2.2, range 13.7-20.1) and had median diabetes duration of 1.3 years. Most were female (65%) and minority race/ethnicity (40% non-Hispanic Black; 10% Hispanic; 5% Asian). Seven (35%) used CGM. The primary benefit elicited was convenience over glucometer use. Important barriers included the impact of physically wearing the device and drawing unwanted attention, desire for AYA privacy, and adequate education about the device.
Discussion: In this diverse sample of AYA with type 2 diabetes and their parents, CGMs were generally regarded as convenient, although concerns about worsening stigma and conflict with parents were prevalent. Our findings can guide the development of patient-centered approaches to CGM use for AYA with type 2 diabetes, a critical step toward reducing inequities in diabetes technology uptake.
Disclosure
V.Peyyety: None. M.Zupa: None. B.Hewitt: None. A.Rodriguez gonzalez: None. I.Mani: None. T.Prioleau: None. J.L.Mccurley: None. Y.Lin: None. M.Vajravelu: None.
Funding
Endocrine Fellows Foundation; National Institutes of Health (K23HL157763, K23DK129724, KL2TR001856, K23DK125719, UL1-TR-001857)
Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes, dyslipidemia, hypertension, ...non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovary syndrome. Children and adolescents with obesity frequently experience weight stigma and have an impaired quality of life, which may exacerbate weight gain. Pediatric obesity is typically defined using sex-, age-, and population-specific body mass index percentiles. Once identified, pediatric obesity should always be managed with lifestyle modification. However, adolescents with obesity may also benefit from anti-obesity medications (AOM), several of which have been approved for use in adolescents by the US Food and Drug Administration, including liraglutide, phentermine/topiramate, and semaglutide. For children with specific, rare monogenic obesity disorders, setmelanotide is available and may lead to significant weight loss. Metabolic and bariatric surgery may be used for the management of severe obesity in youth; though highly effective, it is limited to specialized centers and has had relatively low pediatric uptake. In this narrative review using pediatric-focused data from original research, reviews, clinical practice guidelines, governmental agencies, and pharmaceutical companies, we review obesity-related metabolic complications in youth and management strategies, including AOM and bariatric surgery.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Feeding problems are frequent in infants with congenital hyperinsulinism (HI) and may be exacerbated by continuous enteral nutrition (EN) used to maintain euglycemia. Our center's HI team uses ...dextrose solution given continuously via gastric tube (intrasgastric dextrose, IGD) for infants not fully responsive to conventional medical therapy or pancreatectomy. Here, we describe our practice as well as growth, feeding, and adverse events in infants with HI exposed to IGD.
This was a retrospective cohort of infants with HI treated with IGD from 2009-2017. Primary outcomes were weight-for-length and body mass index Z-scores (WFL-Z and BMI-Z) in the year following IGD initiation. Secondary outcomes included EN use and adverse events. We used multivariable regression to assess covariates of interest.
We studied 32 subjects (13 female) with a median age at IGD initiation of 73 days (range 17-367); median follow-up was 11.2 months (range 5.0-14.2). WFL-Z did not change significantly over time (p > 0.05). EN use decreased significantly over time, i.e., at 0 months: 72% (95% CI 53-85) vs. at 12 months 39% (95% CI 22-59). No potential adverse events led to discontinuation of IGD.
Over a median follow-up of nearly 1 year, IGD was well-tolerated, with no change in WFL-Z or BMI-Z from baseline.
Persistent hypoglycemia in the newborn period most commonly occurs as a result of hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also result from pituitary hormone deficiencies, ...including growth hormone and adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a transcription factor shown in mouse models to influence insulin secretion by pancreatic β cells. In addition, Foxa2 is involved in regulation of pituitary development, and deletions of FOXA2 have been linked to panhypopituitarism.
To describe an infant with congenital hyperinsulinism and hypopituitarism as a result of a mutation in FOXA2 and to determine the functional impact of the identified mutation.
Difference in wild-type (WT) vs mutant Foxa2 transactivation of target genes that are critical for β cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2, NKX2-2, SHH).
Transactivation by mutant Foxa2 of all genes studied was substantially decreased compared with WT.
We report a mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism responsible for this phenotype.
IntroductionAmong youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), ...which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D.Research design and methodsRetrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex.ResultsThe cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D.ConclusionsCOI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth.
Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. ...Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications-biphasic, monophasic, or monotonically increasing-and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8-18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases.
Physical activity is a major component of treatment for adolescents with obesity and prediabetes or type 2 diabetes; however, sedentary behavior remains pervasive. An SMS text message-based ...intervention paired with financial incentives may be an effective way to promote physical activity in this population.
This study aims to obtain end-user feedback on SMS text message content and assess the acceptability of a planned SMS text messaging intervention with financial incentives to motivate youth with prediabetes or type 2 diabetes to increase physical activity.
Adolescents with overweight or obesity and prediabetes or type 2 diabetes who attended a large academic pediatric endocrinology clinic were recruited to participate in group interviews (2-4/group) via videoconferencing. Participants were asked to share their thoughts on the use of SMS text messages and financial incentives to remind and motivate them to be more physically active. They rated and provided feedback on specific messages to be used in clinical trials. Participants were also asked about their personal experience with rewards to motivate behavior change and their anticipated reactions to rewards provided for goal attainment (gain-framing) versus those provided and then taken away if a goal was not met (loss-framing). The interviews were conducted by 2 trained interviewers and a note-taker. Content analysis was used to explore themes.
Group interviews were completed with 20 participants (11/20, 55% women; 15/20, 75% with type 2 diabetes; 5/20, 25% with prediabetes) with a mean age of 15 (SD 1; range 12-18) years and a mean BMI of 41 (SD 5) kg/m
(all >95th percentile for age and sex). Most participants were non-Hispanic Black (14/20, 70%) and 10% (2/20) were Hispanics. Participants frequently cited near-continuous smartphone use and agreed that SMS text messages would serve as good reminders to be physically active, but the consensus about the need for short messages was strong. Favorable content included references to what they were likely to be doing when messages were sent (eg, homework or watching television) and messages that were upbeat or informative. Specific physical activity suggestions were rated favorably. Attitudes toward financial incentives varied, with differing opinions about whether loss-framed incentives would be motivating or discouraging. Many participants highlighted the role of intrinsic, rather than extrinsic, motivation in achieving and sustaining behavior change.
The engagement of adolescents with obesity and diabetes or prediabetes allowed for the refinement of SMS text messages for our planned intervention, with an emphasis on short, upbeat, relatable, and informative messages. Although an SMS text messaging intervention using financial incentives to motivate youth with prediabetes or type 2 diabetes to be more physically active is theoretically acceptable, the impact on actual activity levels in this population requires prospective evaluation in a clinical trial.
Purpose of Review
Adolescence represents a critical time to set habits for long-term health, yet adequate rates of physical activity are uncommon in this age group. Mobile technology use, however, is ...ubiquitous. We review advantages and challenges posed by mobile health (mHealth) and telehealth-based physical activity interventions aimed at adolescents.
Recent Findings
Mobile Health (mHealth) and telehealth interventions to increase physical activity in adolescents include use of wearable activity trackers, text messages or apps, and video visits with exercise specialists. Definitions and goals for physical activity differ across interventions, and methods of activity measurement also vary. User engagement is often poor, if tracked at all. No identified studies included use of behavioral economics-informed engagement strategies.
Summary
Intervention designers must plan for ways to maximize engagement and to reliably measure the intended outcome. Although mHealth and telehealth interventions have advantages such as scalability and acceptability, potential pitfalls must be addressed before widespread implementation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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