Hyperglycemia

Summary

Hyperglycemia (MONDO:0002909) is a disease with 2 cohort genes and 362 clinical trials. Top therapeutic interventions include insulin human, sitagliptin, and ziprasidone.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 362

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperglycemia
Mondo ID	MONDO:0002909
MeSH	D006943
DOID	DOID:4195
SNOMED CT	80394007
UMLS	C0020456
MedGen	5689
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › glucose metabolism disease › hyperglycemia

Related subtypes (8): glucose intolerance, hyperinsulinism, hypoglycemia, diabetes mellitus, prediabetes syndrome, triosephosphate isomerase deficiency, disorder of gluconeogenesis, glyceraldehyde-3-phosphate dehydrogenase deficiency

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
13792	NM_001366110.1(PAX4):c.133C>T (p.Arg45Trp)	PAX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523462	NM_003597.5(KLF11):c.23G>A (p.Gly8Asp)	KLF11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KLF11	Orphanet:552	MODY
PAX4	Orphanet:552	MODY

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KLF11	HGNC:11811	ENSG00000172059	O14901	Krueppel-like factor 11	clinvar
PAX4	HGNC:8618	ENSG00000106331	O43316	Paired box protein Pax-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLF11	Krueppel-like factor 11	Transcription factor.
PAX4	Paired box protein Pax-4	Plays an important role in the differentiation and development of pancreatic islet beta cells.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	2	8.3×	0.015

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLF11	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
PAX4	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1
Brodmann (1909) area 10	1
cerebellar vermis	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLF11	260	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
PAX4	32	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, cerebellar vermis, Brodmann (1909) area 10

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLF11	1,802
PAX4	1,760

Intra-cohort edges

A	B	Sources
KLF11	PAX4	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX4	O43316	70.35
KLF11	O14901	49.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells	1	2284.0×	4e-04	PAX4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
type B pancreatic cell differentiation	1	1053.2×	0.009	PAX4
cellular response to endothelin	1	702.2×	0.009	KLF11
sensory organ development	1	337.0×	0.013	PAX4
forebrain development	1	175.5×	0.015	PAX4
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.015	KLF11
retina development in camera-type eye	1	127.7×	0.015	PAX4
regulation of transcription by RNA polymerase II	2	11.7×	0.015	KLF11, PAX4
animal organ morphogenesis	1	95.8×	0.017	PAX4
brain development	1	39.8×	0.036	PAX4
positive regulation of apoptotic process	1	28.4×	0.045	KLF11
negative regulation of cell population proliferation	1	21.1×	0.055	KLF11
apoptotic process	1	14.3×	0.074	KLF11
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	KLF11

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ginseng, American	Phase 3 (in late-stage trials)
Insulin Glargine	Phase 3 (in late-stage trials)
Insulin Human	Phase 3 (in late-stage trials)
Insulin Lispro	Phase 3 (in late-stage trials)
Insulin Pork	Phase 3 (in late-stage trials)
Insulin Susp Isophane Recombinant Human	Phase 3 (in late-stage trials)
Liraglutide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Exenatide, Insulin Susp Isophane Semisynthetic Purified Human, Lanreotide, Pasireotide.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KLF11	0	0
PAX4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	KLF11, PAX4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KLF11	0	—
PAX4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 362.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	264
PHASE4	41
PHASE3	19
PHASE2	16
PHASE1	10
PHASE1/PHASE2	6
EARLY_PHASE1	4
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05702931	PHASE4	RECRUITING	Semaglutide Treatment for Hyperglycaemia After Renal Transplantation
NCT05835037	PHASE4	RECRUITING	Effect of Zinc on Glucose Homeostasis
NCT07108985	PHASE4	NOT_YET_RECRUITING	Effect of Add-on SGLT2i, TZD, or Combination Therapy in Type 2 Diabetes Patients on DPP4 Inhibitors
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00220987	PHASE4	COMPLETED	Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE - SUGAR STUDY)
NCT00237471	PHASE4	TERMINATED	Impact of Tight Glycaemic Control in Acute Myocardial Infarction
NCT00287820	PHASE4	COMPLETED	Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
NCT00338104	PHASE4	COMPLETED	Conversion of Hyperglycemic Patients Being Treated With Intravenous Insulin Infusions to Lantus Insulin
NCT00362778	PHASE4	COMPLETED	Intensive Insulin Therapy in Non-diabetic Patients With Acute Myocardial Infarction and Hyperglycaemia
NCT00394407	PHASE4	COMPLETED	Basal/Bolus Versus Sliding Scale Insulin In Hospitalized Patients With Type 2 Diabetes
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00736229	PHASE4	COMPLETED	Intravenous Exenatide in Coronary Intensive Care Unit (ICU) Patients
NCT00779701	PHASE4	COMPLETED	Strict Glycemic Control by Insulin Infusion:Observations on Emergency Department Initiation
NCT00859079	PHASE4	COMPLETED	Efficacy of GLP-1 Infusion in Comparison to an Insulin Infusion Protocol to Reach Normoglycemia Type 2 Diabetic Patients
NCT00979628	PHASE4	COMPLETED	Basal Bolus Versus Basal Insulin in Type 2 Diabetes Mellitus (T2DM)
NCT01099618	PHASE4	COMPLETED	Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment
NCT01131052	PHASE4	COMPLETED	Diabetes in the Elderly: Prospective Study
NCT01176279	PHASE4	UNKNOWN	Arterial Catheter to Monitor Glycemia
NCT01184014	PHASE4	COMPLETED	Hospital Insulin Protocol Aims for Glucose Control in Corticosteroid-induced Hyperglycemia
NCT01211730	PHASE4	COMPLETED	Study of Glycemic Control on Liver Transplantation Outcomes
NCT01239004	PHASE4	COMPLETED	Colesevelam Treatment for Impaired Fasting Glucose During Niacin Therapy
NCT01267448	PHASE4	COMPLETED	Outpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia
NCT01378117	PHASE4	COMPLETED	Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes
NCT01625442	PHASE4	COMPLETED	Crocus Sativus (Saffron) and Berberis Vulgaris (Barberry Fruit) in Metabolic Syndrome
NCT01810952	PHASE4	COMPLETED	The Management of Glucocorticoid-Induced Hyperglycemia in Hospitalized Patients
NCT01970462	PHASE4	TERMINATED	Use of Sitagliptin for Stress Hyperglycemia or Mild Diabetes Following Cardiac Surgery
NCT02161055	PHASE4	UNKNOWN	Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury
NCT02165566	PHASE4	COMPLETED	Humalog or Humulin for Intensive Insulin Therapy in Intensive Care Unit
NCT02266264	PHASE4	COMPLETED	Hyperglycemia and Effects of Daily 100 mg Versus 200 mg of Hydrocortisone Therapy in Patients With Septic Shock
NCT02278913	PHASE4	COMPLETED	Basal Bolus Versus Human Insulin in Hospitalized Patients With Diabetes in Paraguay
NCT02349152	PHASE4	COMPLETED	Remifentanil and Glycemic Response in Cardiac Surgery
NCT02491346	PHASE4	UNKNOWN	A Trial Comparing SGC and Conventional Empiric Treatment for Glucose Control in Critically Ill Patients With Mechanical Ventilation in ICU
NCT02556918	PHASE4	COMPLETED	Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery
NCT02741687	PHASE4	COMPLETED	Sitagliptin in Non-Diabetic Patients Undergoing General Surgery
NCT02758522	PHASE4	COMPLETED	NPH and Regular Insulin in the Treatment of Inpatient Hyperglycemia: Comparison of 3 Basal-bolus Regimens
NCT02806999	PHASE4	UNKNOWN	The Therapeutic Effects of Insulin and Berberine on Stress Hyperglycemia
NCT02885909	PHASE4	UNKNOWN	Inpatient Blood Glucose Control in Taichung Veterans General Hospital
NCT04284722	PHASE4	UNKNOWN	Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery
NCT04834362	PHASE4	COMPLETED	Insulin for Hyperglycemia in Stroke Trial
NCT05752929	PHASE4	COMPLETED	Comparison of 2 Hyperglycemia-correction Scales in Hospitalized Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INSULIN HUMAN	4	10
SITAGLIPTIN	4	5
ZIPRASIDONE	4	5
DOPAMINE	4	3
INSULIN LISPRO	4	3
OLANZAPINE	4	3
SAXAGLIPTIN ANHYDROUS	4	3
INSULIN GLARGINE	4	2
INSULIN GLULISINE	4	2
LOSARTAN	4	2
METFORMIN	4	2
AMINO ACIDS	4	1
COLESEVELAM	4	1
CUPRIC SULFATE	4	1
DEXTROSE	4	1
EXENATIDE	4	1
FENTANYL	4	1
GLIPIZIDE	4	1
GLUCAGON	4	1
GLUTAMINE	4	1
GLYCERIN	4	1
HYDROCORTISONE	4	1
LINAGLIPTIN	4	1
MECASERMIN	4	1
PASIREOTIDE	4	1
REMIFENTANIL	4	1
RISPERIDONE	4	1
TENOFOVIR ALAFENAMIDE	4	1
UREA	4	1
LEUCINE	3	2