A case of congenital hyperinsulinism presenting with diabetes after long-term diazoxide therapy.

Congenital hyperinsulinism (CHI) is the most common form of persistent hypoglycemia in infants, and diazoxide is the most widely used drug for its treatment. Diazoxide suppresses insulin secretion and attenuates hypoglycemia by binding to sulfonylurea receptor 1 and activating KATP channels. While the short-term side effects of this drug, such as edema and blood cell abnormalities, are well known, the clinical course after its long-term oral administration remains unclear. Furthermore, there are currently no case reports clearly demonstrating a causal relationship between diazoxide and impaired glucose tolerance. We herein describe the case of a 9-year-old girl with CHI complicated with Kabuki syndrome who presented with impaired glucose tolerance due to decreased initial insulin secretion and insulin resistance caused by obesity resulting from diazoxide medication. This is a rare case of the insufficient effects of insulin due to the oral administration of diazoxide, and provides insights for managing the long-term administration of diazoxide to children.

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins.

We present the case of a 36-year-old female who was diagnosed at birth with CHI that caused severe hypoglycaemia unresponsive to Diazoxide. Subtotal pancreatectomy was performed at the age of three weeks. Later, histological analysis of her pancreas in a research setting revealed a focal form of CHI. Genetic testing was not available at that time. The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. In 2016, a genetic test revealed a missense heterozygous variant in the ABCC8 gene inherited from her father and classified as having a recessive inheritance. The geneticist concluded that the risk of CHI for her offspring would be low (1/600), making pregnancy favourable. As there was no consanguinity in the family, testing the future father was deemed unnecessary (carrier frequency 1/150 in the general population). The pregnancy occurred spontaneously in 2020 and at a gestational age of 28 weeks, the mother went into premature labour. An emergency C-section was performed in April 2021 resulting in the birth of bichorial bi-amniotic male twins. Following birth, both newborns experienced persistent severe hypoglycaemia which required glucagon treatment and intravenous glucose infusion initially, followed by Diazoxide from day 51 after birth, without satisfactory response. Continuous intravenous Octreotide treatment was introduced on day 72. Due to the recurrence of hypoglycaemia episodes despite reaching maximum doses of Octreotide, from day 92 the treatment was switched to Pasireotide. Genetic tests revealed the same genotypes for both infants: the exon 39 missense variant (c.4716C>A; p.Ser1572Arg) inherited from their mother and a truncating variant in exon 28 (c.3550del; p.Val1184*), inherited from their asymptomatic father. As a result of inheriting two recessive variants of the ABCC8 gene, the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. This situation is very rare outside consanguinity. This case emphasises the significance of genetic counselling for individuals with a history of rare diseases outside the context of consanguinity, as there is a potential risk of recurrence. Prenatal diagnosis can lead to better outcomes for affected neonates, as well as help families make informed decisions about future pregnancies.

Clinical management of diazoxide-unresponsive congenital hyperinsulinism: A single-center experience.

The most common cause of persistent hypoglycemia in newborns and children is congenital hyperinsulinism (CHI). Remarkable advancements in diagnostic tools and treatments, including novel imaging and genetic techniques, and continuous subcutaneous octreotide administration, have improved the prognosis of diazoxide-unresponsive CHI; however, in clinical practice, some issues remain. Here, we report a case series consisting of four adenosine triphosphate-sensitive potassium-associated CHI cases, discuss the practical use of new international guidelines published in 2023, and suggest clinical issues associated with CHI management. Based on the clinical experience of two diffuse and two focal CHI cases, we employed an updated treatment strategy, including genetic diagnosis to determine treatment plans, careful catheter management, switching from octreotide to long-acting somatostatin, effective utilization of a continuous glucose monitoring (CGM) device, measures for feeding problems, and individualized and systematic developmental follow-up. Particularly, our cases suggest a safe method of switching from octreotide to lanreotide, elucidate the efficacy of home-based CGM monitoring, and indicate need for personalized support for feeding problems. Severe CHI is a rare and challenging disorder; thus, further accumulation of experience according to new treatment strategies is essential in generating high-quality evidence for the development and approval of new treatment options.

A case of diffuse congenital hyperinsulinism in which continuous glucose monitoring contributed to the choice of a treatment strategy following a subtotal pancreatectomy.

Patients with diffuse congenital hyperinsulinism (CHI) refractory to drug therapy require subtotal or near-total pancreatectomy. Although almost all patients develop diabetes postoperatively, the clinical course and timing of insulin therapy remain unclear. A 7-yr-old girl presented with recurrent hypoglycemia shortly after birth and a relatively elevated insulin level, which confirmed the diagnosis of CHI. Genetic analysis revealed compound heterozygous ATP-binding cassette, Subfamily C, Member 8 pathogenic variants and diffuse CHI was suspected. Because her condition was refractory to diazoxide and octreotide, she underwent a subtotal pancreatectomy at the age of 4 mo. The drug therapy was discontinued. Although an oral glucose tolerance test at the age of 2 yr showed hyperglycemia after loading, continuous glucose monitoring (CGM) revealed that her daily glucose trends were almost within the 70-180 mg/dL range, and mild hypoglycemia appeared during the daytime. After the age of 6 yr, CGM showed an elevation in glucose trends from midnight to early morning, suggesting that insulin secretion was attenuated and hepatic glucose production was insufficiently suppressed. Insulin therapy was initiated at the age of 7 yr. These results indicate that CGM can be useful for making treatment decisions.

Congenital hyperinsulinism and novel KDM6A duplications -resolving pathogenicity with genome and epigenetic analyses.

CONTEXT: Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile -an episignature. OBJECTIVE: We evaluated the pathogenicity of three novel partial KDM6A duplications identified in three individuals presenting with neonatal-onset HI without typical features of KS at the time of genetic testing. METHODS: Three different partial KDM6A duplications were identified by routine targeted next generation sequencing for HI and initially classified as variants of uncertain significance (VUS) as their location, and hence their impact on the gene, was not known. Whole genome sequencing (WGS) was undertaken to map the breakpoints of the duplications with DNA methylation profiling performed in two individuals to investigate the presence of a KS-specific episignature. RESULTS: WGS confirmed the duplication in proband 1 as pathogenic as it caused a frameshift in the normal copy of the gene leading to a premature termination codon. The duplications identified in probands 2 and 3 did not alter the reading frame and therefore their significance remained uncertain after WGS. Subsequent DNA methylation profiling identified a KS-specific episignature in proband 2 but not in proband 3. CONCLUSIONS: Our findings confirm a role for KDM6A partial gene duplications in the etiology of KS and highlight the importance of performing in-depth molecular genetic analysis to properly assess the clinical significance of VUS's in the KDM6A gene.

The Birth Prevalence of Congenital Hyperinsulinism: A Narrative Review of the Epidemiology of a Rare Disease.

BACKGROUND: Congenital hyperinsulinism (HI) is a rare pediatric disease and the most common cause of severe, persistent hypoglycemia in childhood. It is characterized by the dysregulation of insulin secretion from the pancreas and can lead to irreversible brain damage with lifelong neurodisability. SUMMARY: The global birth prevalence of HI is currently unknown. An evidence-based estimate of HI birth prevalence is essential to improve diagnosis and patient management, to drive clinical research and the development of new treatments, and to inform public policy. In order to estimate the birth prevalence of persistent HI, a targeted literature review of studies that report HI epidemiological data was undertaken, and the strengths and limitations of each study were analyzed. Overall, eight global studies were identified that reported independently determined HI epidemiological data. KEY MESSAGES: The best estimate for the birth prevalence of persistent HI in European-ancestry populations is 3.5 per 100,000 births. Local consanguinity patterns appear to have a considerable impact on the birth prevalence of persistent HI in each country, precluding the application of this figure to all global populations. More epidemiological studies with robust methodology are needed to enable a reliable approximation of the incidence and prevalence of HI in global populations.

Non-invasive quantification of stem cell-derived islet graft size and composition.

AIMS/HYPOTHESIS: Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets. We therefore aimed to apply PET as a non-invasive monitoring method for SC-islet grafts. METHODS: We implanted different doses of human SC-islets, SC-islets derived using an older protocol or a state-of-the-art protocol and SC-islets genetically rendered hyper- or hypoactive into mouse calf muscle to yield different kinds of grafts. We followed the grafts with PET using two tracers, glucagon-like peptide 1 receptor-binding [18F]F-dibenzocyclooctyne-exendin-4 ([18F]exendin) and the dopamine precursor 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA), for 5 months, followed by histological assessment of graft size and composition. Additionally, we implanted a kidney subcapsular cohort with different SC-islet doses to assess the connection between C-peptide and stem cell-derived beta cell (SC-beta cell) mass. RESULTS: Small but pure and large but impure grafts were derived from SC-islets. PET imaging allowed detection of SC-islet grafts even <1 mm3 in size, [18F]exendin having a better detection rate than [18F]FDOPA (69% vs 44%, <1 mm3; 96% vs 85%, >1 mm3). Graft volume quantified with [18F]exendin (r2=0.91) and [18F]FDOPA (r2=0.86) strongly correlated with actual graft volume. [18F]exendin PET delineated large cystic structures and its uptake correlated with graft SC-beta cell proportion (r2=0.68). The performance of neither tracer was affected by SC-islet graft hyper- or hypoactivity. C-peptide measurements under fasted or glucose-stimulated conditions did not correlate with SC-islet graft volume or SC-beta cell mass, with C-peptide under hypoglycaemia having a weak correlation with SC-beta cell mass (r2=0.52). CONCLUSIONS/INTERPRETATION: [18F]exendin and [18F]FDOPA PET enable non-invasive assessment of SC-islet graft size and aspects of graft composition. These methods could be leveraged for optimising SC-islet cell replacement therapy in diabetes.

Proposed Screening for Congenital Hyperinsulinism in Newborns: Perspective from a Neonatal-Perinatal Medicine Group.

This perspective work by academic neonatal providers is written specifically for the audience of newborn care providers and neonatologists involved in neonatal hypoglycemia screening. Herein, we propose adding a screen for congenital hyperinsulinism (CHI) by measuring glucose and ketone (i.e., ß-hydroxybutyrate (BOHB)) concentrations just prior to newborn hospital discharge and as close to 48 h after birth as possible, at the same time that the mandated state Newborn Dried Blood Spot Screen is obtained. In the proposed protocol, we do not recommend specific metabolite cutoffs, as our primary objective is to simply highlight the concept of screening for CHI in newborns to newborn caregivers. The premise for our proposed screen is based on the known effect of hyperinsulinism in suppressing ketogenesis, thereby limiting ketone production. We will briefly discuss genetic CHI, other forms of neonatal hypoglycemia, and their shared mechanisms; the mechanism of insulin regulation by functional pancreatic islet cell membrane KATP channels; adverse neurodevelopmental sequelae and brain injury due to missing or delaying the CHI diagnosis; the principles of a good screening test; how current neonatal hypoglycemia screening programs do not fulfill the criteria for being effective screening tests; and our proposed algorithm for screening for CHI in newborns.

Congenital Hyperinsulinism of a Large Italian Cohort: A Retrospective Study.

INTRODUCTION: To evaluate and describe the diagnostic process, medical, nutritional, and surgical approach, and neurological outcome, we report data from a large Italian cohort of patients with congenital hyperinsulinism (CHI). METHODS: We retrospectively analyzed 154 CHI patients admitted to Ospedale Pediatrico Bambino Gesù from 1985 to 2022. RESULTS: Hypoglycemia occurred within the first year of life in 85.5% of patients, median time to diagnosis was 1 day (IQR 14 days). Ninety-two percent of patients were treated with diazoxide: 66.9% were responsive. Octreotide was administered to 28.6% of patients: 61.4% were responsive. Forty percent of patients were off-therapy, mostly from diazoxide. Thirty-four percent of patients carried mutations in ABCC8, 12.6% were syndromic, and 9.2% were transient CHI. Surgery was performed in 23/47 diazoxide-unresponsive and 2/95 diazoxide-responsive patients: 64.0% were focal at histology. Combining data from genetics, pancreatic venous sampling, 18F-DOPA PET/CT, and histology, 80.6% resulted diffuse, 16.7% focal, and 2.8% atypical CHI. Post-surgical diabetes developed in 6 patients. Neurocognitive evaluation revealed developmental delay or intellectual disability in 15.7% of 70 patients, mostly of a mild degree. Epilepsy was documented in 13.7% of 139 patients. CONCLUSION: Our diagnostic and therapeutic results are mainly consistent with the international indications and the CHI Global Registry data, with relatively low rates of neurological outcomes. Good outcomes were likely associated with early diagnosis and prompt management of patients because the majority of patients were diagnosed within 2 weeks. Remarkably, it is of utmost importance to spread the knowledge and refer CHI patients to multidisciplinary expert centers.

Congenital hyperinsulinism and surgical outcome in a single tertiary center in Brazil

Abstract Objective: Congenital hyperinsulinism (CHI) is a heterogeneous genetic disease characterized by increased insulin secretion and causes persistent hypoglycemia in neonates and infants due to dysregulation of insulin secretion by pancreatic β cells. Babies with severe hypoglycemia and for whom medical treatment has been ineffective usually require surgical treatment with near-total pancreatectomy. To evaluate the clinical and surgical aspects affecting survival outcomes in babies diagnosed with CHI in a single tertiary care center. Methods: Retrospective Cohort study involving a single university tertiary center for the treatment of CHI. The authors study the demographics, clinical, laboratory, and surgical outcomes of this casuistic. Results: 61 % were female, 39 % male, Birth weight: 3576 g (±313); Age of onset of symptoms: from the 2nd hour of life to 28 days; Time between diagnosis and surgery ranged between 10 and 60 days; Medical clinical treatment, all patients received glucose solution with a continuous glucose infusion and diazoxide. 81 % of the patients used corticosteroids, 77 %. thiazide, 72 % octreotide, 27 % nifedipine; Neurological sequelae during development and growth: 54 % had some degree of delay in neuropsychomotor development, 27 % obesity. Surgery was performed open in 6 and 12 minimally invasive surgery (MIS). Histopathology: 2 focal and 16 diffuse, Length of stay (days) was lower in MIS (p < 0.05). Survival was 100 %. Conclusions: CHI is a rare and difficult-to-manage tumor that must be performed in a multidisciplinary and tertiary center. Most surgical results are good and the laparoscopic approach to disease has been the best choice for patients.

[Congenital hyperinsulinism : contributions of chemistry, therapeutic response, genetics and imaging]. / Hyperinsulinisme congénital : apports de la biologie, de la réponse thérapeutique, de la génétique et de l'imagerie.

Congenital hyperinsulinism is the most common cause of recurrent hypoglycemia in newborns and children. Early diagnosis and rapid management are essential to avoid hypoglycaemic brain injury and later neurological complications. Management of those patients involves biological evaluation, molecular genetics, imaging techniques and surgical advances. We report the case of a newborn with recurrent hypoglycemia due to congenital hyperinsulinism (CHI) caused by a new variant in the ABCC8 gene. Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography (18F-DOPA PET/CT scan) reported a focal lesion at the isthmus of the pancreas which has been removed by laparoscopic surgery with a complete recovery for the patient.

L'hyperinsulinisme congénital est la cause la plus fréquente d'hypoglycémies récidivantes chez le nouveau-né et l'enfant. Un diagnostic et une prise en charge précoces sont primordiaux pour éviter les conséquences potentielles sur le développement neurologique. Ces derniers reposent sur la conjonction d'éléments biologiques, génétiques et d'imagerie. Nous rapportons le cas d'un nouveau-né présentant des hypoglycémies récidivantes. La mise au point mettra en évidence un hyperinsulinisme congénital (CHI) lié à un variant non encore décrit au sein du gène ABCC8. L'imagerie par Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography/Computed Tomography-scanner (18F-DOPA PET/CT scan) a mis en évidence une forme focale de l'hyperinsulinisme justifiant une prise en charge chirurgicale amenant à une guérison complète et à l'arrêt de tout traitement médicamenteux.

A loss-of-function mutation in KCNJ11 causing sulfonylurea-sensitive diabetes in early adult life.

AIMS/HYPOTHESIS: The ATP-sensitive potassium (KATP) channel couples beta cell electrical activity to glucose-stimulated insulin secretion. Loss-of-function mutations in either the pore-forming (inwardly rectifying potassium channel 6.2 [Kir6.2], encoded by KCNJ11) or regulatory (sulfonylurea receptor 1, encoded by ABCC8) subunits result in congenital hyperinsulinism, whereas gain-of-function mutations cause neonatal diabetes. Here, we report a novel loss-of-function mutation (Ser118Leu) in the pore helix of Kir6.2 paradoxically associated with sulfonylurea-sensitive diabetes that presents in early adult life. METHODS: A 31-year-old woman was diagnosed with mild hyperglycaemia during an employee screen. After three pregnancies, during which she was diagnosed with gestational diabetes, the patient continued to show elevated blood glucose and was treated with glibenclamide (known as glyburide in the USA and Canada) and metformin. Genetic testing identified a heterozygous mutation (S118L) in the KCNJ11 gene. Neither parent was known to have diabetes. We investigated the functional properties and membrane trafficking of mutant and wild-type KATP channels in Xenopus oocytes and in HEK-293T cells, using patch-clamp, two-electrode voltage-clamp and surface expression assays. RESULTS: Functional analysis showed no changes in the ATP sensitivity or metabolic regulation of the mutant channel. However, the Kir6.2-S118L mutation impaired surface expression of the KATP channel by 40%, categorising this as a loss-of-function mutation. CONCLUSIONS/INTERPRETATION: Our data support the increasing evidence that individuals with mild loss-of-function KATP channel mutations may develop insulin deficiency in early adulthood and even frank diabetes in middle age. In this case, the patient may have had hyperinsulinism that escaped detection in early life. Our results support the importance of functional analysis of KATP channel mutations in cases of atypical diabetes.

A synonymous KCNJ11 variant leading to MODY13: A case report and literature review.

Background: Maturity-onset diabetes of the young, type 13 (MODY13) is a specific subclass of monogenic diabetes mellitus that does not exhibit the typical clinical manifestations of diabetes, necessitating the use of genetic testing for accurate diagnosis. With the progression of monogenic diabetes and MODY, the number of reported MODY13 cases has reached a minimum of 22. Nevertheless, there remains a dearth of information regarding patients diagnosed with MODY13 presenting synonymous variants. Case presentation: This study presents a description of the clinical and genetic features of a 9-year-old male patient diagnosed with MODY13. A noteworthy finding in this case was the occurrence of a "separation phenomenon" between C-peptide and insulin during the standard meal test. Whole exome sequencing (WES) identified a KCNJ11 c.843C > T (p.L281=) mutation in exon 1, which contradicted the previously reported phenotype. Following the onset of ketosis, the patient underwent insulin therapy for a duration of one month, during which the insulin dosage was gradually modified based on blood glucose levels. In order to maintain normoglycemia, he adhered to a diabetic dietary regimen and participated in 1-2 h of moderate exercise daily. Conclusion: The study implies that patient with KCNJ11 variant shows a "separation phenomenon" between C-peptide and insulin in standard meal test. Our report also enriched the genotype and phenotype spectrums of MODY13 and highlighted the importance of genetic testing in patients without characteristic clinical symptoms of diabetes.

Functional characterization of inactivating ABCC8 variants causing congenital hyperinsulinism.

Congenital hyperinsulinism (CHI; OMIM: 256450) is characterized by persistent insulin secretion despite severe hypoglycemia. The most common causes are variants in the ATP-binding cassette subfamily C member 8(ABCC8) and potassium inwardly-rectifying channel subfamily J member 11(KCNJ11) genes. These encode ATP-sensitive potassium (KATP) channel subunit sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) proteins. A 7-day-old male infant presented with frequent hypoglycemic episodes and was clinically diagnosed with CHI, underwent trio-whole-exome sequencing, revealing compound heterozygous ABCC8 variants (c.307C>T, p.His103Tyr; and c.3313_3315del, p.Ile1105del) were identified. In human embryonic kidney 293 (HEK293) and rat insulinoma cells (INS-1) transfected with wild-type and variant plasmids, KATP channels formed by p.His103Tyr were delivered to the plasma membrane, whereas p.Ile1105del or double variants (p.His103Tyr coupled with p.Ile1105del) failed to be transported to the plasma membrane. Compared to wild-type channels, the channels formed by the variants (p.His103Tyr; p.Ile1105del) had elevated basal [Ca2+]i, but did not respond to stimulation by glucose. Our results provide evidence that the two ABCC8 variants may be related to CHI owing to defective trafficking and dysfunction of KATP channels.

Congenital hyperinsulinism and surgical outcome in a single tertiary center in Brazil.

OBJECTIVE: Congenital hyperinsulinism (CHI) is a heterogeneous genetic disease characterized by increased insulin secretion and causes persistent hypoglycemia in neonates and infants due to dysregulation of insulin secretion by pancreatic ß cells. Babies with severe hypoglycemia and for whom medical treatment has been ineffective usually require surgical treatment with near-total pancreatectomy. To evaluate the clinical and surgical aspects affecting survival outcomes in babies diagnosed with CHI in a single tertiary care center. METHODS: Retrospective Cohort study involving a single university tertiary center for the treatment of CHI. The authors study the demographics, clinical, laboratory, and surgical outcomes of this casuistic. RESULTS: 61 % were female, 39 % male, Birth weight: 3576 g (±313); Age of onset of symptoms: from the 2nd hour of life to 28 days; Time between diagnosis and surgery ranged between 10 and 60 days; Medical clinical treatment, all patients received glucose solution with a continuous glucose infusion and diazoxide. 81 % of the patients used corticosteroids, 77 %. thiazide, 72 % octreotide, 27 % nifedipine; Neurological sequelae during development and growth: 54 % had some degree of delay in neuropsychomotor development, 27 % obesity. Surgery was performed open in 6 and 12 minimally invasive surgery (MIS). HISTOPATHOLOGY: 2 focal and 16 diffuse, Length of stay (days) was lower in MIS (p < 0.05). Survival was 100 %. CONCLUSIONS: CHI is a rare and difficult-to-manage tumor that must be performed in a multidisciplinary and tertiary center. Most surgical results are good and the laparoscopic approach to disease has been the best choice for patients.

Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children.

CONTEXT: Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI. OBJECTIVE: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC). METHODS: In this open-label trial, patients were randomized 1:1 to SoC or SoC + dasiglucagon (10-70 µg/h) for 4 weeks. In the following 4 weeks, all patients received dasiglucagon + SoC. Hypoglycemia was assessed by self-monitored plasma glucose (SMPG) and blinded continuous glucose monitoring (CGM). Primary endpoint was average number of SMPG-detected hypoglycemia episodes/week (SMPG <3.9 mmol/L) during Weeks 2 to 4. RESULTS: Thirty-two patients (0.6-10.9 years) were randomly assigned to dasiglucagon + SoC (n = 16) or SoC (n = 16). The rate of SMPG-detected hypoglycemia decreased from baseline in both groups, but with no statistically significant difference during Weeks 2 to 4 (event rate ratio: 0.85 [0.54; 1.36], P = .5028). However, dasiglucagon administration resulted in a 43% reduction in CGM-detected hypoglycemia (<3.9 mmol/L) vs SoC alone during Weeks 2 to 4 (post hoc analysis; event rate ratio: 0.57 [0.39; 0.83], P = .0029). Dasiglucagon enabled reductions (of 37% to 61%) in all other measures of hypoglycemia assessed by CGM vs SoC alone including extent and percent time in hypoglycemia (post hoc analyses). Dasiglucagon appeared safe and well tolerated. Skin and gastrointestinal events were more frequent with dasiglucagon + SoC than SoC only. CONCLUSION: Clinically meaningful reductions in all CGM-recorded measures of hypoglycemia support using dasiglucagon as a potential treatment for CHI.

The use of CGM to identify hypoglycemia and glycemic patterns in congenital hyperinsulinism.

OBJECTIVES: Unrecognized hypoglycemia, especially in the neonatal population, is a significant cause of morbidity and poor neurologic outcomes. Children with congenital hyperinsulinism (HI) are at risk of hypoglycemia and point of care testing (POCT) is the standard of care. Studies have shown that continuous glucose monitoring (CGM) improves glycemic control and reduces the frequency of hypoglycemia among children with type 1 diabetes. There is limited experience with the use of CGM in children with HI. To assess the glycemic pattern of children with HI on stable therapy and evaluate the frequency of undetected hypoglycemia using Dexcom G6® CGM. METHODS: A cross-sectional, observational pilot study was done in 10 children, ages 3 months to 17 years. Each child had a clinical or genetic diagnosis of HI on stable medical therapy. Participants were asked to continue their usual POCT blood glucose monitoring, as well as wear a blinded Dexcom G6® CGM during a 20-day study period with the potential of unblinding if there was severe hypoglycemia detected during the study trial. RESULTS: During the study period, 26 hypoglycemic events were noted by CGM in 60 % of the participants with 45 % occurring between 0600 and 0800. CONCLUSIONS: CGM can help detect hypoglycemia and blood glucose trends during a time when there is usually no POCT, which can guide medical management. 30 % of our population had a dose adjustment in their medications. This study was limited by population size.

[Focal congenital hyperinsulinism]. / Focalis congenitalis hyperinsulinismus.

In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.