<p><strong>BACKGROUND: </strong>Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL.</p>

<p><strong>PROCEDURE: </strong>This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose&nbsp;&lt;60&nbsp;mg/dL. Cox regression was used to evaluate the association with age and identify other potential risk factors.</p>

<p><strong>RESULTS: </strong>We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age&nbsp;=&nbsp;0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity&nbsp;=&nbsp;3.50; 95% CI, 1.47-8.36).</p>

<p><strong>CONCLUSIONS: </strong>Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children.</p>

<p><strong>OBJECTIVES: </strong>The objective of this study was to characterize gut microbiome profiles of infants with congenital hyperinsulinism (HI) who underwent near-total or partial pancreatectomy for hypoglycemia management, as compared with healthy controls.</p>

<p><strong>METHODS: </strong>A prospective observational cohort study was performed. Subjects were infants (0-6 months) with HI who underwent removal of pancreatic tissue for management of intractable hypoglycemia from February 2017 to February 2018 at the Children's Hospital of Philadelphia. Fecal samples were collected postoperatively, on full enteral nutrition. The gut microbiome of HI subjects was analyzed and compared with age-matched samples from healthy infants.</p>

<p><strong>RESULTS: </strong>Seven subjects with ≥50% pancreatectomy and 6 with &lt;50% pancreatectomy were included. α (within-sample) diversity was lowest among infants with ≥50% pancreatectomy (richness: false discovery rate, 0.003; Shannon index: false discovery rate, 0.01). β (between-sample) diversity (Bray-Curtis dissimilarity, P = 0.02; Jaccard distance, P = 0.001) differed across groups (≥ or &lt;50% pancreatectomy, controls). Bifidobacteria and Klebsiella species were least abundant among infants with ≥50% pancreatectomy but did not differ between infants with &lt;50% pancreatectomy and historical controls.</p>

<p><strong>CONCLUSIONS: </strong>Infants with HI who underwent ≥50% pancreatectomy differed from age-matched infants in gut microbiome profile, whereas those with &lt;50% pancreatectomy more closely resembled control profiles. The durability of this difference should be investigated.</p>

<p>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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 &gt; 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.</p>

<p><strong>CONCLUSIONS: </strong>Over a median follow-up of nearly 1 year, IGD was well-tolerated, with no change in WFL-Z or BMI-Z from baseline.</p>

<p><strong>PURPOSE OF REVIEW: </strong>Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children. Early and appropriate recognition and treatment of hypoglycemia is vital to minimize neurocognitive impairment.</p>

<p><strong>RECENT FINDINGS: </strong>There are at least 11 known monogenic forms of hyperinsulinism and several associated syndromes. Molecular diagnosis allows for prediction of the effectiveness of diazoxide and the likelihood of focal hyperinsulinism. Inactivating mutations in the genes encoding the ATP-sensitive potassium channel (KATP hyperinsulinism) account for 60% of all identifiable mutations, including 85% of diazoxide-unresponsive cases. Syndromes or disorders associated with hyperinsulinism include Beckwith-Wiedemann syndrome, Kabuki syndrome, Turner syndrome, and congenital disorders of glycosylation. Although focal hyperinsulinism can be cured by resection of the lesion, therapeutic options for nonfocal hyperinsulinism remain limited and include diazoxide, octreotide, long-acting somatostatin analogs, and near-total pancreatectomy. Although sirolimus has been reported to improve glycemic control in infants with diazoxide-unresponsive hyperinsulinism, the extent of improvement has been limited, and significant adverse events have been reported.</p>

<p><strong>SUMMARY: </strong>Identification of the cause of congenital hyperinsulinism helps guide management decisions. Use of therapies with limited benefit and significant potential risks should be avoided.</p>

<p><strong>Context: </strong>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.</p>

<p><strong>Objective: </strong>To determine prevalence of and clinical factors associated with adverse events in infants and children treated with diazoxide.</p>

<p><strong>Design: </strong>Retrospective cohort study of children with hyperinsulinism (HI) treated with diazoxide between 2003 and 2014.</p>

<p><strong>Setting: </strong>The Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia.</p>

<p><strong>Patients: </strong>Children and infants with laboratory-confirmed diagnosis of HI.</p>

<p><strong>Main Outcome Measures: </strong>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.</p>

<p><strong>Results: </strong>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 &lt; 0.0001 and P = 0.005). Other adverse events included neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%).</p>

<p><strong>Conclusion: </strong>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.</p>

<p><strong>OBJECTIVE: </strong>To determine the incidence of and risk factors for development of celiac disese (CD) in individuals with type 1 diabetes.</p>

<p><strong>METHODS: </strong>Cohort study using The Health Improvement Network (THIN), a United Kingdom primary care database of &gt;13 million people. Individuals with incident type 1 diabetes diagnosed at 1-35 years of age between 1995 and 2015 with no previous diagnosis of CD were included. Cox regression was used to identify risk factors for CD, including age at diabetes diagnosis and sex, while adjusting for year of diagnosis to control for potential rising incidence in CD over time.</p>

<p><strong>RESULTS: </strong>Subjects (n=9,180; 43% female) had a median observation time of 5.1 years (IQR 2.0-10.1). CD was diagnosed in 196 (2%) during follow up. Median time to diagnosis was 2.1 years, but 25% were diagnosed more than 5 years after diabetes diagnosis. Incidence (per 10,000 person-years) was greater in females (43.0 [95%CI 35.2-52.0]) vs males (26.8 [95%CI 21.5-32.9]). In multivariable Cox regression stratified by childhood- versus young adult-onset diabetes, younger age at diabetes diagnosis within childhood (HR 0.91 [95% CI 0.88-0.94]) and female sex among the adult-onset diabetes group (HR 3.19 [95% CI 1.39-7.34]) were associated with greater risk of CD.</p>

<p><strong>CONCLUSIONS: </strong>As expected, incidence of CD was higher in individuals with childhood-onset diabetes versus those with adult-onset diabetes. However, individuals with diabetes are at risk of developing CD throughout childhood and adulthood, and prolonged screening after diagnosis may be warranted. Prospective studies are needed in order to guide risk-stratified approaches to screening. This article is protected by copyright. All rights reserved.</p>