Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (827 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A familial, nontransient hypoglycemia with defects in negative feedback of glucose-regulated insulin release. Clinical phenotypes include hypoglycemia; hyperinsulinemia; seizures; COMA; and often large birth weight. Several sub-types exist with the most common, type 1, associated with mutations on an atp-binding cassette transporters (subfamily C, member 8).
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Congenital Hyperinsulinisms; Hyperinsulinisms, Congenital; Familial Hyperinsulinism; Hyperinsulinemia Hypoglycemia of Infancy; Infancy Hyperinsulinemia Hypoglycemias; Hyperinsulinemic Hypoglycemia, Persistent; Hyperinsulinemic Hypoglycemias, Persistent; Hypoglycemia, Persistent Hyperinsulinemic.
Where it fits in the MeSH classification
- Broader topics
- Pancreatic Diseases; Infant, Newborn, Diseases; Hyperinsulinism; Hypoglycemia
- Narrower topics
- Nesidioblastosis
- See also
- ATP-Binding Cassette Transporters; Potassium Channels, Inwardly Rectifying
Related concepts
- Hypoglycemia
- Glucose-
- Insulin
- Hyperinsulinemia
- Seizures
- Birth Weight
- Atp-Binding Cassette Transporters
Research landscape
PubMed indexes 899 records tagged with the MeSH heading “Congenital Hyperinsulinism” (counts retrieved 2026-10-31). 311 of them (34.6%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 411 records.
Reviews account for 169 records (18.8%) and meta-analyses for 4. Randomized controlled trials number 5 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 187 |
| 2010-2019 | 411 |
| 2020 onward | 311 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 169 | 18.8% |
| Meta-analyses | 4 | 0.4% |
| Randomized controlled trials | 5 | 0.6% |
Method: PubMed query "Congenital Hyperinsulinism"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in digestive system and liver
Gut and liver research ranges from laboratory studies of the microbiome to large trials of drugs and surgery. Symptoms such as pain, reflux or bowel change are reported by patients and overlap between conditions, and diet and microbiome studies are mostly observational. Check whether the study measured symptoms, tissue findings or long-term outcomes, how the diagnosis was made and how long people were followed. Nothing here replaces advice from a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes | 2020 | Review article Design not recorded in structured metadata | 146 | cc by PMID 32027066 · DOI · PMC7187370 |
| Congenital Hyperinsulinism: Diagnosis and Treatment Update | 2017 | Review article Design not recorded in structured metadata | 127 | cc by PMID 29280746 · DOI · PMC5790328 |
| International Guidelines for the Diagnosis and Management of Hyperinsulinism | 2024 | Research article Design not recorded in structured metadata | 95 | cc by PMID 37454648 · DOI · PMC11124746 |
| Clinical and Genetic Characteristics of Congenital Hyperinsulinism in Norway: A Nationwide Cohort Study | 2025 | Research article Design not recorded in structured metadata | 14 | cc by PMID 38963811 · DOI · PMC11747666 |
Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11.
- Closing excerpt
- This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (87 words)
The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32027066 · DOI · PMC7187370
Congenital Hyperinsulinism: Diagnosis and Treatment Update [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.
- Closing excerpt
- This review article provides an overview to the background, clinical presentation, diagnosis, molecular genetics and therapy in children with different forms of HH.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (207 words)
Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate secretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH. In HH due to the inhibitory effect of insulin on lipolysis and ketogenesis there is suppressed ketone body formation in the presence of hypoglycaemia thus leading to increased risk of hypoglycaemic brain injury. Therefore, a prompt diagnosis and immediate management of HH is essential to avoid hypoglycaemic brain injury and long-term neurological complications in children. Advances in molecular genetics, imaging techniques (18F-DOPA positron emission tomography/computed tomography scanning), medical therapy and surgical advances (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This review article provides an overview to the background, clinical presentation, diagnosis, molecular genetics and therapy in children with different forms of HH.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29280746 · DOI · PMC5790328
International Guidelines for the Diagnosis and Management of Hyperinsulinism [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundHyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children.
- Closing excerpt
- The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (285 words)
BackgroundHyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide.SummaryRecent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in "developed" countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use.Key messagesThis international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37454648 · DOI · PMC11124746
Clinical and Genetic Characteristics of Congenital Hyperinsulinism in Norway: A Nationwide Cohort Study [4]
Abstract reading summary — source excerpts
- Opening excerpt
- PurposeCongenital hyperinsulinism (CHI) is a rare, monogenic disease characterized by excessive insulin secretion.
- Closing excerpt
- Patients with known genetic etiology had earlier and more severe disease onset than genetically unsolved patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (248 words)
PurposeCongenital hyperinsulinism (CHI) is a rare, monogenic disease characterized by excessive insulin secretion. We aimed to evaluate all probands with suspected CHI in Norway registered over the past 2 decades.MethodsThe study included 98 probands. Clinical data were cumulated from medical records. All probands were screened for variants in the genes ABCC8 and KCNJ11. Other CHI-related genes were Sanger-sequenced as indicated by the patients' phenotype (n = 75) or analyzed by next-generation sequencing employing a panel of 30 CHI-related genes (n = 23).ResultsTwenty-one probands (21%) received a diagnosis other than CHI, the most common being idiopathic ketotic hypoglycemia (9%) or syndromic hyperinsulinism (4%). In the final cohort of 77 CHI probands, genetic findings were revealed in 46 (60%). ABCC8 variants were most common (n= 40), and 5 novel variants were identified. One proband harbored both the pathogenic GCK variant p.(Ala456Val) and the ABCC8 variant p.(Gly505Cys). Although most ABCC8 variants caused immediate disease onset with severe hypoglycemia and were diazoxide-unresponsive, 8 probands had a heterozygous, apparently dominant variant with milder phenotype. Two probands had pathogenic variants in GLUD1, whereas variants in HADH, HNF4A, KCNJ11, and HK1 were identified in 1 proband each, the latter being noncoding. Neurologic sequelae were reported in 53% of the CHI probands. Of nonsurgically treated probands, 43% had spontaneous resolution. The minimum birth prevalence of CHI in Norway is 1:19,400 live births.Main conclusionIndividuals with disease-causing ABCC8 variants dominated our cohort. Patients with known genetic etiology had earlier and more severe disease onset than genetically unsolved patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38963811 · DOI · PMC11747666
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia [5]
- Research article Congenital hyperinsulinism: current trends in diagnosis and therapy [6]
- Research article Hyperinsulinism in infancy: from basic science to clinical disease [7]
- Research article Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders [8]
- Research article Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia [9]
- Research article Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates [10]
References
- De Franco E, Saint-Martin C, Brusgaard K, Knight Johnson AE, Aguilar-Bryan L, Bowman P, et al.. Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. . 2020. PMID 32027066 · DOI · PMC7187370
- Demirbilek H, Hussain K. Congenital Hyperinsulinism: Diagnosis and Treatment Update. . 2017. PMID 29280746 · DOI · PMC5790328
- De Leon DD, Arnoux JB, Banerjee I, Bergada I, Bhatti T, Conwell LS, et al.. International Guidelines for the Diagnosis and Management of Hyperinsulinism. . 2024. PMID 37454648 · DOI · PMC11124746
- Velde CD, Molnes J, Berland S, Njølstad PR, Molven A. Clinical and Genetic Characteristics of Congenital Hyperinsulinism in Norway: A Nationwide Cohort Study. . 2025. PMID 38963811 · DOI · PMC11747666
- Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, et al.. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat. 2009. PMID 19790256 · DOI
- Arnoux JB, Verkarre V, Saint-Martin C, Montravers F, Brassier A, Valayannopoulos V, et al.. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis. 2011. PMID 21967988 · DOI · PMC3199232
- Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ. Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev. 2004. PMID 14715916 · DOI
- Stanley CA. Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders. J Clin Endocrinol Metab. 2016. PMID 26908106 · DOI · PMC4803157
- Banerjee I, Salomon-Estebanez M, Shah P, Nicholson J, Cosgrove KE, Dunne MJ. Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia. Diabet Med. 2019. PMID 30246418 · DOI · PMC6585719
- De León DD, Stanley CA. Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007. PMID 17179930 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
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