Hyperinsulinism

Summary

Hyperinsulinism (MONDO:0002177) is a disease caused by variants in FOXA2 and HK1, with 6 cohort genes and 36 clinical trials. Top therapeutic interventions include clomiphene, mecasermin, and diazoxide.

At a glance

• Causal genes: FOXA2 (GenCC Strong), HK1 (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 14
• Clinical trials: 36

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperinsulinism
Mondo ID	MONDO:0002177
MeSH	D006946
DOID	DOID:2018
ICD-11	224022886
SNOMED CT	83469008
UMLS	C0020459
MedGen	43779
Is cancer (heuristic)	no

Also known as: hyperinsulinism · hyperinsulinism (disease)

Data availability: 14 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › hyperinsulinism

Related subtypes (11): gastrin secretion abnormality, abnormality of glucagon secretion, post-surgical hypoinsulinemia, pancreatic cholera, diabetes mellitus, aggressive insulitis, benign insulitis, pancreatic neuroendocrine neoplasm, islet cell adenomatosis, insulin-resistance syndrome type A, insulin-resistance syndrome type B

Subtypes (1): familial hyperinsulinism

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

7 conflicting classifications of pathogenicity, 3 pathogenic, 3 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
156152	NM_175914.5(HNF4A):c.187C>T (p.Arg63Trp)	HNF4A	Pathogenic	reviewed by expert panel
36364	NM_175914.5(HNF4A):c.925C>T (p.Arg309Cys)	HNF4A	Pathogenic	reviewed by expert panel
8666	NM_000525.4(KCNJ11):c.602G>A (p.Arg201His)	KCNJ11	Pathogenic	criteria provided, multiple submitters, no conflicts
373928	NM_000525.4(KCNJ11):c.185C>G (p.Thr62Arg)	KCNJ11	Likely pathogenic	no assertion criteria provided
157687	NM_000352.6(ABCC8):c.207T>C (p.Pro69=)	ABCC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
35612	NM_000352.6(ABCC8):c.4120-19C>T	ABCC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158672	NM_000525.4(KCNJ11):c.1143G>A (p.Lys381=)	KCNJ11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211227	NM_000525.4(KCNJ11):c.843C>T (p.Leu281=)	KCNJ11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211230	NM_000525.4(KCNJ11):c.881C>T (p.Thr294Met)	KCNJ11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435556	NM_000525.4(KCNJ11):c.868G>A (p.Val290Met)	KCNJ11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8684	NM_000525.4(KCNJ11):c.466G>A (p.Gly156Arg)	KCNJ11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30135	NM_000525.4(KCNJ11):c.179T>A (p.Phe60Tyr)	KCNJ11	Uncertain significance	criteria provided, single submitter
549538	NM_000525.4(KCNJ11):c.794G>T (p.Ser265Ile)	KCNJ11	Uncertain significance	criteria provided, multiple submitters, no conflicts
556784	NM_000525.4(KCNJ11):c.662G>A (p.Arg221His)	KCNJ11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 37 · Orphanet: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FOXA2	Strong	Autosomal dominant	hyperinsulinism	2
HK1	Strong	Autosomal dominant	hyperinsulinism	16
KCNA4	Strong	Autosomal dominant	hyperinsulinism	19

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HK1	Orphanet:90031	Non-spherocytic hemolytic anemia due to hexokinase deficiency
HK1	Orphanet:99953	Charcot-Marie-Tooth disease type 4G
FOXA2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
HNF4A	Orphanet:263455	Congenital hyperinsulinism due to HNF4A deficiency
HNF4A	Orphanet:544628	Atypical Fanconi syndrome-neonatal hyperinsulinism syndrome
HNF4A	Orphanet:552	MODY
ABCC8	Orphanet:276575	Autosomal dominant hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:276598	Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:552	MODY
ABCC8	Orphanet:79134	DEND syndrome
ABCC8	Orphanet:79643	Autosomal recessive hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
ABCC8	Orphanet:99886	Transient neonatal diabetes mellitus
KCNJ11	Orphanet:276580	Autosomal dominant hyperinsulinism due to Kir6.2 deficiency
KCNJ11	Orphanet:276603	Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency
KCNJ11	Orphanet:552	MODY
KCNJ11	Orphanet:79134	DEND syndrome
KCNJ11	Orphanet:79644	Autosomal recessive hyperinsulinism due to Kir6.2 deficiency
KCNJ11	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
KCNJ11	Orphanet:99886	Transient neonatal diabetes mellitus
KCNJ11	Orphanet:99989	Intermediate DEND syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HK1	HGNC:4922	ENSG00000156515	P19367	Hexokinase-1	gencc
FOXA2	HGNC:5022	ENSG00000125798	Q9Y261	Hepatocyte nuclear factor 3-beta	gencc
KCNA4	HGNC:6222	ENSG00000182255	P22459	Potassium voltage-gated channel subfamily A member 4	gencc
HNF4A	HGNC:5024	ENSG00000101076	P41235	Hepatocyte nuclear factor 4-alpha	clinvar
ABCC8	HGNC:59	ENSG00000006071	Q09428	ATP-binding cassette sub-family C member 8	clinvar
KCNJ11	HGNC:6257	ENSG00000187486	Q14654	ATP-sensitive inward rectifier potassium channel 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HK1	Hexokinase-1	Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-p…
FOXA2	Hepatocyte nuclear factor 3-beta	Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues.
KCNA4	Potassium voltage-gated channel subfamily A member 4	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
HNF4A	Hepatocyte nuclear factor 4-alpha	Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes.
ABCC8	ATP-binding cassette sub-family C member 8	Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release.
KCNJ11	ATP-sensitive inward rectifier potassium channel 11	Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many different cells.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.83

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	2	37.2×	0.006
Nuclear receptor	1	64.3×	0.039
Transporter	1	13.0×	0.124
Kinase	1	4.6×	0.247
Transcription factor	1	1.4×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HK1	Kinase	yes	2.7.1.1	Hexokinase, Hexokinase_BS, Hexokinase_N
FOXA2	Transcription factor	no		Fork_head_dom, Fork-head_N, TF_fork_head_CS_1
KCNA4	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
HNF4A	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
ABCC8	Transporter	yes		ABCC8/9, ABCC8, ABC_transporter-like_ATP-bd
KCNJ11	Ion channel	yes		K_chnl_inward-rec_Kir6.2, K_chnl_inward-rec_Kir_cyto, Ig_E-set

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar vermis	1
pharyngeal mucosa	1
pons	1
buccal mucosa cell	1
pancreatic ductal cell	1
pylorus	1
adrenal tissue	1
nucleus accumbens	1
secondary oocyte	1
duodenum	1
mucosa of transverse colon	1
right lobe of liver	1
cerebellar hemisphere	1
islet of Langerhans	1
right hemisphere of cerebellum	1
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HK1	291	ubiquitous	marker	cerebellar vermis, pharyngeal mucosa, pons
FOXA2	105	broad	marker	pancreatic ductal cell, pylorus, buccal mucosa cell
KCNA4	142	broad	marker	adrenal tissue, nucleus accumbens, secondary oocyte
HNF4A	110	tissue_specific	marker	right lobe of liver, mucosa of transverse colon, duodenum
ABCC8	185	broad	marker	islet of Langerhans, right hemisphere of cerebellum, cerebellar hemisphere
KCNJ11	161	broad	yes	gastrocnemius, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNF4A	4,731
ABCC8	2,826
FOXA2	2,789
KCNA4	2,311
HK1	2,298
KCNJ11	1,715

Intra-cohort edges

A	B	Sources
ABCC8	FOXA2	string_interaction
ABCC8	KCNJ11	biogrid_interaction, intact, string_interaction
FOXA2	HNF4A	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HK1	P19367	10
KCNJ11	Q14654	9
HNF4A	P41235	8
ABCC8	Q09428	8
FOXA2	Q9Y261	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNA4	P22459	70.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 6 evidence-associated genes (6 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCC8 can cause hypo- and hyper-glycemias	2	1903.3×	7e-06	ABCC8, KCNJ11
ATP sensitive Potassium channels	2	951.7×	2e-05	ABCC8, KCNJ11
Potassium Channels	3	67.2×	8e-05	ABCC8, KCNA4, KCNJ11
Inwardly rectifying K+ channels	2	237.9×	2e-04	ABCC8, KCNJ11
Regulation of gene expression in beta cells	2	173.0×	3e-04	FOXA2, HNF4A
ABC transporter disorders	2	146.4×	4e-04	ABCC8, KCNJ11
Neuronal System	3	22.1×	9e-04	ABCC8, KCNA4, KCNJ11
Regulation of insulin secretion	2	73.2×	0.001	ABCC8, KCNJ11
Integration of energy metabolism	2	58.6×	0.002	ABCC8, KCNJ11
Defective HK1 causes hexokinase deficiency (HK deficiency)	1	1903.3×	0.002	HK1
Disorders of transmembrane transporters	2	46.4×	0.002	ABCC8, KCNJ11
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	951.7×	0.003	KCNJ11
Synthesis of GDP-mannose	1	317.2×	0.007	HK1
Positive Regulation of CDH1 Gene Transcription	1	158.6×	0.013	FOXA2
Nephron development	1	146.4×	0.014	HNF4A
Formation of axial mesoderm	1	135.9×	0.014	FOXA2
Formation of definitive endoderm	1	119.0×	0.015	FOXA2
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	100.2×	0.017	FOXA2
Developmental Lineage of Pancreatic Acinar Cells	1	50.1×	0.031	FOXA2
Glycolysis	1	47.6×	0.031	HK1
Voltage gated Potassium channels	1	40.5×	0.035	KCNA4
Developmental Lineage of Pancreatic Ductal Cells	1	38.1×	0.035	FOXA2
Ion homeostasis	1	34.0×	0.037	KCNJ11
Nuclear Receptor transcription pathway	1	33.4×	0.037	HNF4A
ABC-family protein mediated transport	1	20.2×	0.058	KCNJ11
Cardiac conduction	1	18.1×	0.062	KCNJ11
Disease	2	4.4×	0.079	ABCC8, KCNJ11
Muscle contraction	1	12.9×	0.081	KCNJ11
Metabolism	2	3.9×	0.091	ABCC8, KCNJ11
Transport of small molecules	1	4.2×	0.216	KCNJ11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of insulin secretion	3	195.9×	2e-05	HNF4A, ABCC8, KCNJ11
action potential	3	179.3×	2e-05	ABCC8, KCNA4, KCNJ11
potassium ion transmembrane transport	3	68.0×	2e-04	ABCC8, KCNA4, KCNJ11
obsolete inorganic cation transmembrane transport	2	312.1×	4e-04	ABCC8, KCNJ11
intracellular glucose homeostasis	2	193.7×	8e-04	HK1, ABCC8
negative regulation of insulin secretion	2	165.2×	9e-04	ABCC8, KCNJ11
cellular response to nutrient levels	2	156.0×	9e-04	ABCC8, KCNJ11
potassium ion import across plasma membrane	2	122.1×	0.001	ABCC8, KCNJ11
glucose metabolic process	2	85.1×	0.002	HK1, KCNJ11
regulation of growth hormone receptor signaling pathway	1	2808.7×	0.003	HNF4A
negative regulation of neuroblast migration	1	2808.7×	0.003	ABCC8
obsolete regulation of ornithine metabolic process	1	2808.7×	0.003	HNF4A
positive regulation of uterine smooth muscle relaxation	1	2808.7×	0.003	ABCC8
potassium ion transport	2	63.8×	0.003	ABCC8, KCNA4
glutamate secretion, neurotransmission	1	936.2×	0.006	ABCC8
obsolete GDP-mannose biosynthetic process from mannose	1	936.2×	0.006	HK1
negative regulation of blood-brain barrier permeability	1	936.2×	0.006	ABCC8
response to interleukin-6	1	702.2×	0.008	FOXA2
response to resveratrol	1	561.7×	0.008	KCNJ11
positive regulation of tight junction disassembly	1	561.7×	0.008	ABCC8
response to pH	1	468.1×	0.008	ABCC8
GDP-mannose biosynthetic process	1	468.1×	0.008	HK1
regulation of gastrulation	1	468.1×	0.008	HNF4A
CAMKK-AMPK signaling cascade	1	468.1×	0.008	KCNJ11
obsolete establishment of protein localization to mitochondrion	1	468.1×	0.008	HK1
maintenance of protein location in mitochondrion	1	468.1×	0.008	HK1
positive regulation of gastrulation	1	401.2×	0.009	FOXA2
ventricular cardiac muscle tissue development	1	351.1×	0.009	KCNJ11
mannose metabolic process	1	351.1×	0.009	HK1
positive regulation of potassium ion transport	1	351.1×	0.009	ABCC8

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Diazoxide	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Mecasermin.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 5 of 6 evidence-associated genes (83%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC8	REPAGLINIDE
KCNJ11	PINACIDIL ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNJ11	7	4
ABCC8	6	4
HK1	1	3
FOXA2	0	0
KCNA4	0	0
HNF4A	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
REPAGLINIDE	4	ABCC8
DIAZOXIDE	4	ABCC8, KCNJ11
GLYBURIDE	4	ABCC8, KCNJ11
PINACIDIL ANHYDROUS	4	KCNJ11
PROPAFENONE	4	KCNJ11
EBSELEN	3	HK1
CROMAKALIM	2	ABCC8, KCNJ11
CLAMIKALANT	2	ABCC8, KCNJ11
TIFENAZOXIDE	2	ABCC8, KCNJ11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HNF4A	106	Binding:97, Functional:9
KCNJ11	102	Functional:59, Binding:43
ABCC8	84	Functional:52, Binding:32
KCNA4	30	Binding:26, ADMET:2, Toxicity:1, Functional:1
HK1	12	Binding:9, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HK1	2.7.1.1	hexokinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HNF4A	106
KCNJ11	102

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

8 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
REPAGLINIDE	4	ABCC8
GLYBURIDE	4	ABCC8, KCNJ11
PINACIDIL ANHYDROUS	4	KCNJ11
PROPAFENONE	4	KCNJ11
EBSELEN	3	HK1
CROMAKALIM	2	ABCC8, KCNJ11
CLAMIKALANT	2	ABCC8, KCNJ11
TIFENAZOXIDE	2	ABCC8, KCNJ11

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ABCC8, KCNJ11
B	Phased (≥1) drug, not yet approved	1	HK1
C	Druggable family + PDB, no drug	1	HNF4A
D	Druggable family + AlphaFold only, no drug	1	KCNA4
E	Difficult family or no structure, no drug	1	FOXA2

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HNF4A	106	—
FOXA2	0	—
KCNA4	30	—

Clinical trials & evidence

Clinical trials

Clinical trials: 36.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	27
PHASE2	6
PHASE1/PHASE2	1
EARLY_PHASE1	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05088798	PHASE2	RECRUITING	Utility of 18FDOPA PET/MRI for Focal Hyperinsulinism
NCT00004700	PHASE2	COMPLETED	Phase II Long Term, Randomized Study of Recombinant Human Insulin-like Growth Factor I in Children With Hyperinsulinism
NCT00151684	PHASE2	COMPLETED	Diazoxide-Mediated Insulin Suppression in Hyperinsulinemic Obese Men
NCT00674440	PHASE2	COMPLETED	Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism
NCT02524639	PHASE1/PHASE2	WITHDRAWN	Sirolimus for the Treatment of Hyperinsulinism
NCT03053284	PHASE2	WITHDRAWN	Pasireotide in Hyperinsulinemic Hypoglycemia
NCT04062890	PHASE2	WITHDRAWN	Inhibiting GABA Transaminase to Relieve Obesity Induced Hyperinsulinemia and Insulin Resistance
NCT05989347	PHASE1	RECRUITING	Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy
NCT05753657	EARLY_PHASE1	RECRUITING	A Pilot Study of Monitoring Insulin Levels and Treating Hyperinsulinemia and Hyperglycemia With Pioglitazone in Patients Treated With Alpelisib for Metastatic Breast Cancer.
NCT05543083	Not specified	RECRUITING	Cognitive-Behavioral Therapy and Exercise Training in Adolescents At-Risk for Type 2 Diabetes
NCT05662189	Not specified	RECRUITING	Assessment of Pancreatic Beta Cell Mass and Function by Positron Emission Tomography Imaging in Human Diabetes Mellitus
NCT05764200	Not specified	RECRUITING	Acute Microbial Switch
NCT05950282	Not specified	RECRUITING	Determinants of Insulin Sensitivity by Age, Sex, Race/Ethnicity, BMI, and PCOS Diagnosis
NCT06478121	Not specified	RECRUITING	Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
NCT06889454	Not specified	RECRUITING	Cardiovascular and Endothelial Markers During OGTT Before and at Six and Twelve Months Post-treatment in Women With PCOS
NCT00004699	Not specified	COMPLETED	Dose Ranging Study of Recombinant Human Insulin-like Growth Factor I in Children With Hyperinsulinism
NCT00004825	Not specified	COMPLETED	Short Term Study of Recombinant Human Insulin-like Growth Factor I in Children With Hyperinsulinism
NCT00005104	Not specified	COMPLETED	Randomized Study of Decreased Hyperinsulinemia on the Ovulatory Response to Clomiphene Citrate in Women With Polycystic Ovary Syndrome
NCT00005365	Not specified	COMPLETED	Central Obesity and Disease Risk in Japanese Americans
NCT00005380	Not specified	COMPLETED	Insulin, Androgen, and Risk in African-American Women
NCT00005530	Not specified	COMPLETED	Diet, Insulin Resistance, and Cardiovascular Risk
NCT00005654	Not specified	COMPLETED	Randomized Study of the Effect of Decreased Hyperinsulinemia on the Ovulatory Response to Clomiphene Citrate in Obese Women With Polycystic Ovary Syndrome
NCT00005709	Not specified	COMPLETED	Lipoprotein Metabolism in Hypertensive African-Americans
NCT00073775	Not specified	COMPLETED	Epidemiology of Stress and the Metabolic Syndrome
NCT00074451	Not specified	COMPLETED	Genomewide Search for Loci Underlying Metabolic Syndrome
NCT00937079	Not specified	COMPLETED	Whole Body 111In-exendin-4 Imaging Study in Insulinoma Patients
NCT02248272	Not specified	COMPLETED	Effect of Meal Frequency on Glycemic Control of People at High Risk or Diagnosed With Diabetes
NCT03303196	Not specified	COMPLETED	Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes
NCT03358745	Not specified	COMPLETED	Impact of Meal Order on Postprandial Cardiometabolic Risk Markers
NCT03856606	Not specified	COMPLETED	The Effects of Interrupting Prolonged Sitting With Intermittent Exercise on Postprandial Lipemia
NCT04327245	Not specified	COMPLETED	To Compare the Effects of Non-nutritive Sweeteners Intake in Woman With Insulin Resistance
NCT04744896	Not specified	UNKNOWN	Effects Of Combined Cryolipolysis And High Intensity Interval Training On Insulin Resistance And Body Composition In Polycystic Ovarian Patients
NCT05329337	Not specified	COMPLETED	Link Between the Peripheral Mononuclear Cells’ Capacity to Induce Insulin Resistance and Hyperinsulinemia
NCT05528874	Not specified	COMPLETED	NUTRACORE, Glycaemic Index and Appetite
NCT05774613	Not specified	UNKNOWN	Effect of Hibiscus Sabdariffa Beverage
NCT06363929	Not specified	TERMINATED	Continuous Glucose Monitoring in Neonatal Hyperinsulinism

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CLOMIPHENE	4	4
MECASERMIN	4	2
DIAZOXIDE	4	1
SIROLIMUS	4	1
VIGABATRIN	4	1
ENCLOMIPHENE CITRATE	3	2
TAGATOSE	3	1