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.
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
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)
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.
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)
Background: The Health Belief Model (HBM) posits that perception of threat, cues to act, and benefits/barriers drive health behaviors. We evaluated whether this association exists in adolescents at ...risk for type 2 diabetes. Methods: Cross-sectional analysis of youth 12-17 years old with overweight/obesity (BMI>85th percentile) without known diabetes in the US National Health and Nutrition Examination Survey 2011-2018. We used linear and logistic regression to evaluate potential predictors of diabetes risk-reducing health behaviors, adjusting for age, sex, race/ethnicity, and BMI Z-score. Predictors included: 1) perceived threat ("feel at risk for diabetes"), 2) cues to act (told of diabetes risk or prediabetes by health care provider), and 3) barriers (household size, food security). Results: The sample included 1,497 individuals representing 9,613,219 US youth. Overall, 16% (95% CI 14,19%) felt at risk for diabetes, and 20% (95% CI 18,24%) reported being told they were at risk for diabetes or had prediabetes. Older age (OR 1.2; 95% CI 1.0,1.3, per year) and higher BMI Z-score (OR 5; 95% CI 3,7) were associated with feeling at greater risk. Self-perceived risk was associated with 1 less day per week of >60 minutes of physical activity (beta=-1.0; 95% CI -1.7,-0.3). Being cued to diabetes risk was not associated with differences in physical activity or nutrition. Non-full food security was associated with nearly 1 less day per week with >60 minutes of physical activity (beta=-0.8; 95% CI -1.4,-0.3), while higher income to poverty ratio was associated with more days per week with >60 minutes of physical activity (beta=0.2; 95% CI 0.02,0.4). Conclusions: In a US-representative sample of adolescents with overweight/obesity, perceived risk of diabetes did not drive behavior. Instead, age, BMI, and self-reported physical activity influenced risk perception. Being informed of diabetes risk, alone, was not associated with diabetes risk-reducing behaviors.
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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.
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.
Summary
Background
Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti‐obesity pharmacotherapy for ...adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated.
Objectives
To model changes in obesity prevalence with increasing utilization of anti‐obesity pharmacotherapy among adolescents.
Methods
Data representative of American adolescents ages 12–17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre‐pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%–100%, stratified by race and ethnicity.
Results
Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non‐Hispanic White youth, with prevalence among Non‐Hispanic Black and Mexican American youth ranging from 40%–60% higher to 90%–120% higher, respectively.
Conclusions
Increasing utilization of anti‐obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity‐related disparities.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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