KPD
MCID: DBT084
MIFTS: 60

Diabetes Mellitus, Ketosis-Prone (KPD)

Categories: Blood diseases, Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Diabetes Mellitus, Ketosis-Prone

MalaCards integrated aliases for Diabetes Mellitus, Ketosis-Prone:

Name: Diabetes Mellitus, Ketosis-Prone 57 12 75 29 13 40
Diabetic Ketoacidosis 12 55 44 15 73
Diabetes Mellitus, Ketosis-Prone, Susceptibility to 57 6
Ketosis-Prone Diabetes Mellitus 12 37
Kpd 57 75
Diabetes Mellitus, Insulin-Dependent 73

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant (in 1 patient)

Miscellaneous:
hla class ii alleles specify ketosis-prone diabetes (kpd) subgroup
near-normoglycemic remission for period of months to years without insulin treatment


HPO:

32

Classifications:



External Ids:

OMIM 57 612227
Disease Ontology 12 DOID:1837
ICD9CM 35 250.1
NCIt 50 C50530
SNOMED-CT 68 24927004
KEGG 37 H01224

Summaries for Diabetes Mellitus, Ketosis-Prone

OMIM : 57 In addition to classic type 1 (see 222100) and type 2 (see 125853) diabetes mellitus, atypical presentations are seen, particularly in populations of African ancestry. Ketosis-prone diabetes, the most common atypical form, is characterized by an acute initial presentation with severe hyperglycemia and ketosis, as seen in classic type 1 diabetes, but after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies show a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic beta-cell autoimmunity is a rare finding, and association with type 1 susceptibility HLA alleles is variable (Sobngwi et al., 2002). (612227)

MalaCards based summary : Diabetes Mellitus, Ketosis-Prone, also known as diabetic ketoacidosis, is related to monocarboxylate transporter 1 deficiency and diabetes mellitus, insulin-dependent, and has symptoms including polydipsia and polyuria. An important gene associated with Diabetes Mellitus, Ketosis-Prone is PAX4 (Paired Box 4), and among its related pathways/superpathways are Glucose / Energy Metabolism and Butanoate metabolism. The drugs Metformin and Insulin, Globin Zinc have been mentioned in the context of this disorder. Affiliated tissues include brain, kidney and liver, and related phenotypes are diabetes mellitus and autoimmunity

UniProtKB/Swiss-Prot : 75 Diabetes mellitus, ketosis-prone: An atypical form of diabetes mellitus characterized by an acute initial presentation with severe hyperglycemia and ketosis, as seen in classic type 1 diabetes, but after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies show a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic beta-cell autoimmunity is a rare finding.

Wikipedia : 76 Ketosis-prone diabetes or KPD is an intermediate form of diabetes that has some characteristics of type... more...

Related Diseases for Diabetes Mellitus, Ketosis-Prone

Diseases related to Diabetes Mellitus, Ketosis-Prone via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 235)
# Related Disease Score Top Affiliating Genes
1 monocarboxylate transporter 1 deficiency 30.6 GAD1 INS
2 diabetes mellitus, insulin-dependent 29.9 GAD1 GAD2 INS PAX4 SLC30A10
3 diabetes mellitus, noninsulin-dependent 29.7 ACACA GAD2 INS PAX4 SLC30A8 SLC5A2
4 diabetes mellitus 29.6 GAD1 GAD2 INS PAX4 PIK3C2A SLC30A8
5 autoimmune disease 29.4 GAD1 GAD2 INS
6 metabolic acidosis 10.4
7 hypoglycemia 10.3
8 hyperglycemia 10.3
9 hypophosphatemia 10.3
10 acromegaly 10.3
11 acute pancreatitis 10.2
12 pancreatitis 10.2
13 hypokalemia 10.2
14 encephalopathy 10.2
15 mucormycosis 10.2
16 maturity-onset diabetes of the young, type 9 10.2 INS PAX4
17 respiratory failure 10.2
18 autoimmune polyendocrine syndrome 10.1 GAD1 GAD2
19 type 1 diabetes mellitus 13 10.1 GAD2 INS
20 maturity-onset diabetes of the young, type 13 10.1 INS PAX4
21 hypertriglyceridemia, familial 10.1
22 myocardial infarction 10.1
23 hypertriglyceridemia, transient infantile 10.1
24 brain injury 10.1
25 thrombosis 10.1
26 lactic acidosis 10.1
27 spastic cerebral palsy 10.1 GAD1 GAD2
28 methylmalonic aciduria due to methylmalonyl-coa mutase deficiency 10.1
29 pancreas adenocarcinoma 10.1
30 adenocarcinoma 10.1
31 brain edema 10.1
32 extrapontine myelinolysis 10.1
33 monogenic diabetes 10.1 INS PAX4
34 sarcocystosis 10.1 GAD1 PIK3C2A
35 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 10.1 GAD1 GAD2
36 limbic encephalitis 10.0 GAD1 GAD2
37 autoimmune polyendocrine syndrome, type ii 10.0 GAD1 GAD2 INS
38 stiff-person syndrome 10.0 GAD1 GAD2 INS
39 acquired metabolic disease 10.0 GAD2 INS SLC5A2
40 pheochromocytoma 10.0
41 thrombophilia due to thrombin defect 10.0
42 isovaleric acidemia 10.0
43 moyamoya disease 1 10.0
44 graves disease 1 10.0
45 stroke, ischemic 10.0
46 dengue hemorrhagic fever 10.0
47 hepatitis 10.0
48 renal tubular acidosis 10.0
49 somatostatinoma 10.0
50 cardiac arrest 10.0

Comorbidity relations with Diabetes Mellitus, Ketosis-Prone via Phenotypic Disease Network (PDN):


Acute Cystitis Decubitus Ulcer
Heart Disease Hypertension, Essential
Ischemic Heart Disease

Graphical network of the top 20 diseases related to Diabetes Mellitus, Ketosis-Prone:



Diseases related to Diabetes Mellitus, Ketosis-Prone

Symptoms & Phenotypes for Diabetes Mellitus, Ketosis-Prone

Symptoms via clinical synopsis from OMIM:

57
Metabolic Features:
ketoacidosis
insulin resistance, variable

Immunology:
autoimmunity to pancreatic beta cells (rare)

Abdomen Pancreas:
beta-cell dysfunction of varying degrees


Clinical features from OMIM:

612227

Human phenotypes related to Diabetes Mellitus, Ketosis-Prone:

32
# Description HPO Frequency HPO Source Accession
1 diabetes mellitus 32 HP:0000819
2 autoimmunity 32 HP:0002960
3 insulin resistance 32 HP:0000855
4 ketoacidosis 32 HP:0001993
5 beta-cell dysfunction 32 HP:0006279

UMLS symptoms related to Diabetes Mellitus, Ketosis-Prone:


polydipsia, polyuria

MGI Mouse Phenotypes related to Diabetes Mellitus, Ketosis-Prone:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.81 ACACA GAD1 GAD2 INS PAX4 PIK3C2A
2 endocrine/exocrine gland MP:0005379 9.73 GAD1 GAD2 INS PAX4 SLC30A10 SLC30A8
3 homeostasis/metabolism MP:0005376 9.61 ACACA GAD1 GAD2 INS PAX4 PIK3C2A
4 no phenotypic analysis MP:0003012 9.02 GAD1 GAD2 INS SLC30A8 SLC5A2

Drugs & Therapeutics for Diabetes Mellitus, Ketosis-Prone

Drugs for Diabetes Mellitus, Ketosis-Prone (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 32)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Metformin Approved Phase 4 657-24-9 14219 4091
2 Insulin, Globin Zinc Phase 4
3 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
4 HIV Protease Inhibitors Phase 4
5 Sitagliptin Phosphate Phase 4
6 Incretins Phase 4
7 insulin Phase 4
8 Hormone Antagonists Phase 4
9 Hormones Phase 4
10 Dipeptidyl-Peptidase IV Inhibitors Phase 4
11 Hypoglycemic Agents Phase 4
12
protease inhibitors Phase 4
13
Nitric Oxide Approved Not Applicable 10102-43-9 145068
14
Pioglitazone Approved, Investigational 111025-46-8 4829
15 Vasodilator Agents Not Applicable
16 Anti-Asthmatic Agents Not Applicable
17 alanine Not Applicable
18 Neurotransmitter Agents Not Applicable
19 Antioxidants Not Applicable
20 Bronchodilator Agents Not Applicable
21 Protective Agents Not Applicable
22 Free Radical Scavengers Not Applicable
23 arginine Not Applicable
24 Respiratory System Agents Not Applicable
25 Peripheral Nervous System Agents Not Applicable
26 Endothelium-Dependent Relaxing Factors Not Applicable
27 Autonomic Agents Not Applicable
28 Fat Emulsions, Intravenous Not Applicable
29 Soy Bean Not Applicable
30 Soybean oil, phospholipid emulsion Not Applicable
31 Pharmaceutical Solutions Not Applicable
32 Parenteral Nutrition Solutions Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment Completed NCT01099618 Phase 4 metformin;placebo;Sitagliptin
2 Study of Arginine and Nitric Oxide in Patients With Diabetes Recruiting NCT03566524 Not Applicable
3 Ketosis Prone Diabetes in African-Americans Completed NCT00426413 pioglitazone
4 Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises Completed NCT00753142 Not Applicable Intralipid 20%;Glucose infusion

Search NIH Clinical Center for Diabetes Mellitus, Ketosis-Prone

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: diabetic ketoacidosis

Genetic Tests for Diabetes Mellitus, Ketosis-Prone

Genetic tests related to Diabetes Mellitus, Ketosis-Prone:

# Genetic test Affiliating Genes
1 Diabetes Mellitus, Ketosis-Prone 29 PAX4

Anatomical Context for Diabetes Mellitus, Ketosis-Prone

MalaCards organs/tissues related to Diabetes Mellitus, Ketosis-Prone:

41
Brain, Kidney, Liver, Testes, Bone, Thyroid, Lung

Publications for Diabetes Mellitus, Ketosis-Prone

Articles related to Diabetes Mellitus, Ketosis-Prone:

(show top 50) (show all 1272)
# Title Authors Year
1
Scrub typhus initially manifested as diabetic ketoacidosis: A case report. ( 29872635 )
2018
2
Respiratory failure in a diabetic ketoacidosis patient with severe hypophosphatemia. ( 29969883 )
2018
3
Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in Type 1 diabetes mellitus: a systematic review. ( 28945942 )
2018
4
Impact of the hyperchloremic component of metabolic acidosis on the patient's hydration status and the treatment of diabetic ketoacidosis. ( 29756707 )
2018
5
Central Pontine Myelinolysis in Pediatric Diabetic Ketoacidosis. ( 29973999 )
2018
6
Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis. ( 30159178 )
2018
7
Prediabetes Directly Deteriorates into Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome Triggered by Acute Pancreatitis: A Case Report Illustrating a "Chicken and Egg" Paradigm in Ketosis-Prone Diabetes. ( 29600506 )
2018
8
Acute pancreatitis secondary to hypertriglyceridemia precipitated by diabetic ketoacidosis in a previously undiagnosed ketosis-prone patient with diabetes mellitus. ( 29706815 )
2018
9
In diabetic ketoacidosis brain injury including cerebral oedema and infarction is caused by interleukin-1. ( 30396487 )
2018
10
Management of Diabetic Ketoacidosis with Dengue Hemorrhagic Fever. ( 30473969 )
2018
11
Type I Brugada pattern associated with diabetic ketoacidosis in a patient with type II diabetes mellitus. ( 30520428 )
2018
12
Low hemoglobin A1c levels in a patient with diabetic ketoacidosis: Fulminant type 1 diabetes mellitus. ( 30325130 )
2018
13
Diabetic ketoacidosis masquerading as pre-eclampsia: a case report. ( 28760066 )
2018
14
Can diabetic ketoacidosis (DKA) precipitate posterior reversible encephalopathy syndrome (PRES)? ( 29675562 )
2018
15
Neuroinflammation-Related Encephalopathy in an Infant Born Preterm Following Exposure to Maternal Diabetic Ketoacidosis. ( 29555093 )
2018
16
Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES-SCI) as a rare complication of severe diabetic ketoacidosis: a case report and review of the literature. ( 29330587 )
2018
17
Endogenous bacterial endophthalmitis and subretinal abscess complicating diabetic ketoacidosis. ( 30232080 )
2018
18
Extrapontine Myelinolysis and Microhemorrhages: Rare Finding in Pediatric Diabetic Ketoacidosis. ( 30396831 )
2018
19
Sodium-glucose Cotransporter-2 Induced Diabetic Ketoacidosis with Minimal Hyperglycemia. ( 29849291 )
2018
20
A diabetic ketoacidosis in a context of hyperglycemia addiction. ( 29034415 )
2018
21
Severe hypoglycemia and diabetic ketoacidosis in young persons with preschool onset of type 1 diabetes mellitus: An analysis of three nationwide population-based surveys. ( 29498171 )
2018
22
Successful treatment of life-threatening severe metabolic acidosis by continuous veno-venous hemodialysis in a child with diabetic ketoacidosis. ( 30130252 )
2018
23
Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy. ( 30094785 )
2018
24
A Case of Persistent Vegetative State after Diabetic Ketoacidosis Triggered by an Overdose of Psychotropic Agents. ( 30210110 )
2018
25
Thrombotic Thrombocytopenic Purpura in a Child with Diabetic Ketoacidosis. ( 29531931 )
2018
26
Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis. ( 29576870 )
2018
27
Diabetic ketoacidosis further increases risk of Alzheimer's disease in patients with type 2 diabetes. ( 30481578 )
2018
28
A brief campaign to prevent diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: The NO-DKA Study. ( 30014558 )
2018
29
Access to a youth-specific service for young adults with type 1 diabetes mellitus is associated with decreased hospital length of stay for diabetic ketoacidosis. ( 29034986 )
2018
30
Development and Implementation of a Diabetic Ketoacidosis Protocol for Adults With Type 1 and Type 2 Diabetes at a Tertiary Care Multicampus Hospital. ( 30414784 )
2018
31
Fluid treatment for children with diabetic ketoacidosis: How do the results of the pediatric emergency care applied research network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (FLUID) Trial change our perspective? ( 30417497 )
2018
32
Diabetic ketoacidosis following PEG-asparaginase therapy ( 30427164 )
2018
33
Reversible Blindness as Presenting Manifestation of Severe Diabetic Ketoacidosis. ( 30454845 )
2018
34
Biochemical Differences Between Vitreous Humor and Cerebral Spinal Fluid in a Death From Diabetic Ketoacidosis. ( 30475235 )
2018
35
Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review. ( 30479686 )
2018
36
Diabetic Ketoacidosis Associated with Thyroxine (T₄) Toxicosis and Thyrotoxic Cardiomyopathy. ( 30486325 )
2018
37
Reversible blindness secondary to severe diabetic ketoacidosis. ( 30488886 )
2018
38
Utilizing serum bicarbonate instead of venous pH to transition from intravenous to subcutaneous insulin shortens the duration of insulin infusion in pediatric diabetic ketoacidosis. ( 30530908 )
2018
39
Brugada Pattern in Diabetic Ketoacidosis: A Case Report and Scoping Study. ( 30533520 )
2018
40
Effect of Bolus Insulin Administration Followed by a Continuous Insulin Infusion on Diabetic Ketoacidosis Management. ( 30544554 )
2018
41
Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes and Glycemic Control over Time: The SEARCH for Diabetes in Youth Study. ( 30556249 )
2018
42
Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters. ( 29316133 )
2018
43
Unusual cause of severe diabetic ketoacidosis precipitated by Streptococcus bovis/equinus (SBSEC) bacteremia: Case report and review of literature. ( 29349041 )
2018
44
RE: DIABETIC KETOACIDOSIS IN PATIENTS WITH TYPE 2 DIABETES ON SGLT-2 INHIBITORS: AN ONGOING CONCERN. ( 29368970 )
2018
45
Evaluating an Order Set for Improvement of Quality Outcomes in Diabetic Ketoacidosis. ( 29384776 )
2018
46
Trends in Hospital Admission for Diabetic Ketoacidosis in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study. ( 29386248 )
2018
47
Basal Subnuclear Vacuolization, Armanni-Ebstein Lesions, Wischnewsky Lesions, and Elevated Vitreous Glucose and β-Hydroxybuyrate: Is It Hypothermia, Diabetic Ketoacidosis, or Both? ( 29401111 )
2018
48
Quetiapine-induced Diabetic Ketoacidosis. ( 29403139 )
2018
49
Sodium-glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis; from Pathophysiology to Clinical Practice. ( 29412120 )
2018
50
Preoperative steroids triggering diabetic ketoacidosis in the neurosurgical patient. ( 29414610 )
2018

Variations for Diabetes Mellitus, Ketosis-Prone

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Ketosis-Prone:

75
# Symbol AA change Variation ID SNP ID
1 PAX4 p.Arg45Trp VAR_054880
2 PAX4 p.Arg141Trp VAR_054882 rs2233578

ClinVar genetic disease variations for Diabetes Mellitus, Ketosis-Prone:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PAX4 NM_006193.2(PAX4): c.397C> T (p.Arg133Trp) single nucleotide variant risk factor rs2233578 GRCh37 Chromosome 7, 127254551: 127254551
2 PAX4 NM_006193.2(PAX4): c.397C> T (p.Arg133Trp) single nucleotide variant risk factor rs2233578 GRCh38 Chromosome 7, 127614497: 127614497
3 PAX4 NM_006193.2(PAX4): c.109C> T (p.Arg37Trp) single nucleotide variant Uncertain significance rs35155575 GRCh37 Chromosome 7, 127255466: 127255466
4 PAX4 NM_006193.2(PAX4): c.109C> T (p.Arg37Trp) single nucleotide variant Uncertain significance rs35155575 GRCh38 Chromosome 7, 127615412: 127615412

Expression for Diabetes Mellitus, Ketosis-Prone

Search GEO for disease gene expression data for Diabetes Mellitus, Ketosis-Prone.

Pathways for Diabetes Mellitus, Ketosis-Prone

GO Terms for Diabetes Mellitus, Ketosis-Prone

Cellular components related to Diabetes Mellitus, Ketosis-Prone according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 inhibitory synapse GO:0060077 8.96 GAD1 GAD2
2 clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane GO:0061202 8.62 GAD1 GAD2

Biological processes related to Diabetes Mellitus, Ketosis-Prone according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.61 GAD1 GAD2 PAX4
2 epidermal growth factor receptor signaling pathway GO:0007173 9.4 PIK3C2A SLC30A10
3 positive regulation of cell differentiation GO:0045597 9.37 INS PAX4
4 zinc ion transport GO:0006829 9.32 SLC30A10 SLC30A8
5 carboxylic acid metabolic process GO:0019752 9.26 GAD1 GAD2
6 neurotransmitter biosynthetic process GO:0042136 9.16 GAD1 GAD2
7 negative regulation of reactive oxygen species biosynthetic process GO:1903427 8.96 INS SLC30A10
8 glutamate decarboxylation to succinate GO:0006540 8.62 GAD1 GAD2

Molecular functions related to Diabetes Mellitus, Ketosis-Prone according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pyridoxal phosphate binding GO:0030170 9.32 GAD1 GAD2
2 carboxy-lyase activity GO:0016831 9.26 GAD1 GAD2
3 cation transmembrane transporter activity GO:0008324 9.16 SLC30A10 SLC30A8
4 glutamate binding GO:0016595 8.96 GAD1 GAD2
5 glutamate decarboxylase activity GO:0004351 8.62 GAD1 GAD2

Sources for Diabetes Mellitus, Ketosis-Prone

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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