Type 2 Maturity-Onset Diabetes of the Young

A hereditary autosomal dominant form of type 2 diabetes mellitus that typically occurs before 25 years of age and is caused by primary INSULIN secretion defects. MODY2 is caused by mutations in the GCK gene. OMIM: 125851

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Networked: 169 relevant articles (1 outcomes, 16 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Type 2 Diabetes Mellitus (MODY)
2.	Type 3 Maturity-Onset Diabetes of the Young
3.	Type 1 Maturity-Onset Diabetes of the Young
4.	Type 2 Maturity-Onset Diabetes of the Young
5.	Mason-Type Diabetes

Experts

1.	Hansen, Torben: 4 articles (08/2015 - 04/2002)
2.	Molnes, Janne: 3 articles (10/2021 - 10/2008)
3.	Njølstad, Pål R: 3 articles (10/2021 - 06/2006)
4.	Sagen, Jørn V: 3 articles (10/2021 - 06/2006)
5.	Bjørkhaug, Lise: 3 articles (01/2020 - 06/2006)
6.	Li, Ming: 3 articles (08/2019 - 12/2018)
7.	Navas, María-Angeles: 3 articles (07/2018 - 01/2006)
8.	Vincent, Olivier: 3 articles (07/2018 - 01/2006)
9.	Cao, Henian: 3 articles (12/2016 - 12/2002)
10.	Hegele, Robert A: 3 articles (12/2016 - 12/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Type 2 Maturity-Onset Diabetes of the Young:

1.	Glucagon (Glukagon)FDA Link 08/01/2015 - "All of the groups exhibited similar baseline values of glucagon (MODY2: 7 ± 1 pmol/l; MODY3: 6 ± 1 pmol/l; CTRLs: 8 ± 2 pmol/l, P=0.787), but patients with MODY3 exhibited postprandial hyperglucagonaemia (area under the curve (AUC) 838 ± 108 min × pmol/l) as compared to CTRLs (182 ± 176 min × pmol/l, P=0.005) and tended to have a greater response than did patients with MODY2 (410 ± 154 min × pmol/l, P=0.063). " 01/31/1998 - "No clinical parameter was helpful in classifying patients in one of these subclasses of diabetes; however, glucagon stimulated C-peptide was useful in discriminating between MODY2 patients and the others. " 04/01/1997 - "No clinical parameter was helpful to classify patients in one of these subclasses of diabetes; however, the glucagon-stimulated C-peptide was useful to discriminate between MODY2 patients and the others. " 08/01/2015 - "The pathophysiology of MODY3 includes exaggerated postprandial glucagon responses and increased fasting DPP4 enzymatic activity but normal postprandial incretin responses both in patients with MODY2 and in patients with MODY3." 11/01/2000 - "During progressive hypoglycemia, the glycemic thresholds of MODY2 patients for increasing glucose production (5.0 +/- 0.4 mmol.l(- 1) ) and for glucagon stimulation (4.5 +/- 0.4 mmol. "
2.	C-PeptideIBA 08/01/2019 - "The ROC-derived fasting C-peptide levels for discriminating MODY2 from T1D and MODY3 from T1D were 0.951 and 0.975, respectively. " 01/31/1998 - "No clinical parameter was helpful in classifying patients in one of these subclasses of diabetes; however, glucagon stimulated C-peptide was useful in discriminating between MODY2 patients and the others. " 03/01/2010 - "We report a case of MODY2 caused by a novel GCK mutation and demonstrate differential glycemic/C-peptide responses to treatment with insulin, no medication, and an oral sulfonylurea." 03/01/2010 - "A novel glucokinase gene mutation and its effect on glycemic/C-peptide fluctuations in a patient with maturity-onset diabetes of the young type 2." 04/01/1997 - "No clinical parameter was helpful to classify patients in one of these subclasses of diabetes; however, the glucagon-stimulated C-peptide was useful to discriminate between MODY2 patients and the others. "
3.	GlucokinaseIBA 01/01/2013 - "Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study." 08/13/2022 - "Taken together, glucokinase ubiquitination and degradation signaling might be impaired in MODY2 patients." 07/30/2021 - "MODY2 is caused by heterozygous inactivating mutations in the glucokinase (GCK) gene that result in persistent, stable and mild fasting hyperglycaemia (5.6-8.0 mmol/L, glycosylated haemoglobin range of 5.6-7.3%). " 08/01/2016 - "Analysis of mutations in the glucokinase gene in people clinically characterized as MODY2 without a family history of diabetes." 07/01/2016 - "We diagnose MODY2 diabetes due to a glucokinase gene mutation. "
4.	Hepatocyte Nuclear Factor 1-alpha (Hepatocyte Nuclear Factor 1 alpha)IBA 04/01/2000 - "Mutations in the GCK/MODY2 and HNF-1alpha/MODY3 genes account for the majority of cases in a panel of Spanish MODY families, with MODY3 being the most frequent subtype. " 09/01/1999 - "Among 115 Scandinavian families, mutations in the HNF-1alpha gene represented the most common cause of familial early-onset ( </= 40 years) diabetes: MODY3 (5.2 %) more than MODY2 (3.5 %) more than MIDD (2.6 %) more than MODY1 (1.7 %)." 02/01/2003 - "The aim of this study was to examine the prevalence and nature of mutations in HNF4alpha/MODY1, GCK/MODY2 and HNF-1alpha/MODY3 genes in Czech subjects with clinical diagnosis of MODY. " 02/01/2003 - "We identified 20 different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families (48% of all families studied), giving a relative prevalence of 5% of MODY1, 31% of MODY2 and 11.5% of MODY3 among the Czech kindred with MODY. " 12/01/2016 - "The 39 mutation-positive samples had 1 of 39 rare variants, of which the majority were in genes encoding either glucokinase (GCK, or MODY2) or hepatocyte nuclear factor 1-alpha (HNF1A, or MODY3). "
5.	Proteins (Proteins, Gene)FDA Link 08/01/1999 - "The enzymatic activity and thermal stability of wild-type (WT) GK and several mutant forms associated with maturity-onset diabetes of the young type 2 (MODY-2) were determined by a steady-state kinetic analysis of the purified expressed proteins. " 07/01/2010 - "Glucokinase gene E339K mutation promotes the development of MODY2 by affecting protein yield and protein stability as well as the enzymatic kinetics of GCK." 01/01/2006 - "MODY2 is caused by mutations in the glucokinase gene, which encodes the signal protein for insulin secretion. " 06/01/2006 - "Our study provides further evidence that protein instability in combination with loss of control by a putative endogenous activator and GKRP could be involved in the development of hyperglycemia in maturity-onset diabetes of the young, type 2. Furthermore, based on data obtained on G264S, we propose that other and still unknown mechanisms participate in the regulation of glucokinase." 10/31/2023 - "Next, we analyzed glucokinase variant proteins from MODY2 or persistent hyperinsulinemic hypoglycemia in infancy (PHHI). "
6.	Transcription Factors (Transcription Factor)IBA 12/01/2002 - "Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. " 12/05/1996 - "Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. " 08/01/2006 - "These include the enzyme glucokinase, which causes MODY2, and the transcription factors HNF- 4 alpha, TCF1, I PF-1, TCF2, and NeuroD1, which cause MODY1, 3, 4, 5, and 6, respectively. " 04/01/1997 - "Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form. " 05/01/1999 - "To date, five proteins have been identified whose genetic absence or impairment causes MODY, the enzyme glucokinase (GCK/MODY2) and four transcription factors: hepatocyte nuclear factor 4alpha (HNF-4alpha/MODY1), HNF-1alpha/MODY3, insulin promoter factor 1 (IPF-1/MODY4) and HNF-1beta/MODY5. "
7.	Nonsense Codon (Nonsense Mutation)IBA 01/10/2013 - "In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). " 09/01/2009 - "In this study 100 diabetic Jordanian patients with MODY2 phenotype and 150 Normal control subjects were screened for the presence of GCK gene mutations including the missense mutations at position Thr228Ala in exon 7, Gly299Arg in exon 8 and nonsense mutation Ser383Ter in exon 9, utilizing polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis. "
8.	Glucose (Dextrose)FDA LinkGeneric 01/01/2013 - "Molecular docking study revealed variation in docking scores (intact = -12.199 and mutated = -8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition." 07/01/2008 - "Glucose tolerance can remain stable over many years in subjects with MODY2 due to the relative stability of the GCK-related beta-cell defect. " 07/01/2005 - "MODY2 is characterized by glucose sensing defects, leading to an increase in insulin secretion threshold. " 01/01/2021 - "In addition, aTL showed a negative correlation with duration of the disease and fasting plasma glucose (FPG) levels in MODY patients in general and also with HbA1c in MODY2 patients in particular. " 07/01/2008 - "We report an 11-year follow-up of glucose tolerance and indexes of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects. "
9.	EnzymesIBA 01/01/2012 - "All mutations except p.Glu70Asp displayed thermal-instability, indeed >50% of enzyme activity was lost at 50°C/30 min. Thus, these seven mutations play a pathogenic role in MODY2 insurgence. " 09/01/2009 - "The mutation in the gene encoding GCK results in enzyme inactivation cause MODY2. " 02/01/2007 - "In the gene encoding GCK the heterozygous mutations that result in enzyme inactivation cause MODY2. " 06/01/2004 - "This collection of Gk mutants will be valuable for understanding GK gene function, for dissecting the function of the enzyme and as models of human MODY2 and PNDM." 10/01/2011 - "MODY2 is caused by heterozygous mutations in the GCK gene that encodes the glucokinase enzyme. "
10.	Hepatocyte Nuclear FactorsIBA 06/01/2004 - "MODY2 and MODY3, the glucokinase (GCK) and the hepatocyte nuclear factor (HNF)-1alpha gene is affected, respectively. " 10/01/2006 - "Maturity-onset diabetes of the young (MODY) is mostly caused by mutations of the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in Caucasians. " 04/01/2005 - "In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. " 03/01/1997 - "To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). " 08/01/2005 - "Direct sequencing of NEUROD1 was performed in (i) 73 probands with clinical MODY without mutations in hepatocyte nuclear factor (HNF)-4alpha (MODY1), glucokinase (MODY2) and hepatocyte nuclear factor (HNF)-1alpha (MODY3), and (ii) 51 subjects diagnosed with gestational diabetes. "

Therapies and Procedures

1.	Therapeutics 07/01/2006 - "The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations."
2.	Ligation 01/01/2021 - "Genetic screening for MODY1 (HNF4α), MODY2 (GCK), MODY3 (HNF1α), and MODY5 (HNF1β) was performed by direct sequencing followed by multiplex ligation amplification assays. "
3.	Drug Therapy (Chemotherapy) 09/04/2015 - "Thus, a glucokinase activator drug therapy may help MODY2 patients not in general, but seems to be a useful strategy for carriers of the L315H glucokinase mutation. "