Type 3 Maturity-Onset Diabetes of the Young

A form of familial noninsulin-dependent diabetes mellitus (diabetes mellitus, type 2) that is characterized by an early age of onset (childhood, adolescence, or young adulthood under 25 years) and autosomal dominant inheritance. Mutations in the HNF1A gene have been identified. OMIM: 600496

Also Known As:

Networked: 219 relevant articles (3 outcomes, 26 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

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

Experts

1.	Groop, L: 7 articles (09/2013 - 12/2000)
2.	Hansen, Torben: 6 articles (01/2018 - 04/2002)
3.	Bjørkhaug, Lise: 5 articles (01/2022 - 02/2003)
4.	Njølstad, P R: 5 articles (12/2016 - 12/2000)
5.	Njølstad, Pål R: 4 articles (10/2021 - 02/2003)
6.	Vilsbøll, Tina: 4 articles (01/2018 - 07/2014)
7.	Pedersen, Oluf: 4 articles (08/2015 - 04/2004)
8.	Gragnoli, Claudia: 4 articles (07/2015 - 11/2007)
9.	Wollheim, Claes B: 4 articles (11/2010 - 06/2002)
10.	Søvik, O: 4 articles (07/2008 - 12/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Type 3 Maturity-Onset Diabetes of the Young:

1.	Glucose (Dextrose)FDA LinkGeneric 11/01/1996 - "The present study was undertaken to define the interactions between glucose and insulin secretion rate (ISR) in subjects with mutations in MODY3. " 02/26/2022 - "The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control. " 01/01/2021 - "Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells." 01/01/2020 - "Response to multiple glucose-lowering agents in a sib-pair with a novel HNF1α (MODY3) variant." 08/01/2015 - "43 ± 5 years; BMI 24 ± 2 kg/m(2); fasting plasma glucose (FPG) 7.1 ± 0.3 mmol/l: HbA1c 6.6 ± 0.2%), ten patients with MODY3 (age 31 ± 3 years; BMI 24 ± 1 kg/m(2); FPG 8.9 ± 0.8 mmol/l; HbA1c 7.0 ± 0.3%) and ten CTRLs (age 40 ± 5 years; BMI 24 ± 1 kg/m(2); FPG 5.1 ± 0.1 mmol/l; HbA1c 5.3 ± 0.1%) were examined with a liquid test meal. "
2.	Nateglinide (Starlix)FDA LinkGeneric 02/01/2006 - "Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3." 02/01/2006 - "To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas. " 02/01/2006 - "We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. "
3.	Glyburide (Glibenclamide)FDA LinkGeneric 12/01/2002 - "Decreased glibenclamide uptake in hepatocytes of hepatocyte nuclear factor-1alpha-deficient mice: a mechanism for hypersensitivity to sulfonylurea therapy in patients with maturity-onset diabetes of the young, type 3 (MODY3)." 04/01/2005 - "Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity. " 02/01/2006 - "Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3." 02/01/2006 - "We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. "
4.	Sodium-Glucose Transporter 2 InhibitorsIBA 12/01/2021 - "SGLT2 inhibitors may be an effective treatment for achieving glycaemic control in individuals with MODY3." 12/01/2021 - "This case suggests that SGLT2 inhibitors may be an effective and potent treatment option in addition to sulfonylureas for individuals with MODY3. " 12/01/2021 - "The use of SGLT2 inhibitors in achieving glycaemic control in maturity-onset diabetes of the young type 3." 12/01/2021 - "Paradoxically, despite individuals with MODY3 having reduced expression of SGLT2, SGLT2 inhibitors induce higher glycosuria in individuals with MODY3 compared to individuals with type 2 diabetes mellitus. " 12/01/2021 - "This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin. "
5.	Hepatocyte Nuclear Factor 1-alpha (Hepatocyte Nuclear Factor 1 alpha)IBA 01/01/2017 - "Over the past years, several studies have reported the association of missense mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A) with MODY3. " 12/01/2006 - "This study provides in vitro and in vivo evidence that common variants in the MODY3 gene, HNF-1alpha, influence transcriptional activity and insulin secretion in vivo. " 01/01/2017 - "Hepatocyte nuclear factor 1 alpha (HNF1α) defects cause Mature Onset Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell insulin secretion. " 05/01/2014 - "Gene defects in the Hepatocyte Nuclear Factor -1 alpha (HNF1a) causes MODY3. " 12/01/2008 - "Although its etiology and natural history have not been fully elucidated, germline mutation of hepatocyte nuclear factor 1alpha, which is associated with maturity-onset diabetes of the young type 3, has recently been implicated in a subset of cases. "
6.	Hepatocyte Nuclear FactorsIBA 06/30/2022 - "In this study, we reported a case of MODY3, which was verified to be caused by a mutation in hepatocyte nuclear factor 1α gene (c.598C>T, p.Arg200Trp). " 01/01/2023 - "Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation." 11/01/2015 - "However, different polymorphisms were identified, with I27L (42.9%; 12/28) and S487N (46.4%; 13/28) of hepatocyte nuclear factor 4α (HNF1α/MODY3) being two most frequent polymorphisms. " 01/01/2015 - "[Hepatocyte nuclear factor 1α-inactivated hepatocellular adenomatosis in a patient with maturity-onset diabetes of the young type 3: case report and literature review]." 11/12/2010 - "Heterozygous loss-of-function mutations in the hepatocyte nuclear factor 1A (HNF1A) gene result in the pathogenesis of maturity-onset diabetes-of-the-young type 3, (HNF1A-MODY). "
7.	Transcription Factors (Transcription Factor)IBA 01/01/2022 - "Structural and biophysical characterization of transcription factor HNF-1A as a tool to study MODY3 diabetes variants." 01/01/2023 - "MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. " 01/01/2019 - "Here, we use genome edited human embryonic stem cells to understand the most common form of monogenic diabetes, MODY3, caused by mutations in the transcription factor HNF1A. " 02/01/2011 - "Hnf1α (MODY3) regulates β-cell-enriched MafA transcription factor expression." 12/21/2020 - "Molecular Dynamics Simulations Predict That rSNP Located in the HNF‑1α Gene Promotor Region Linked with MODY3 and Hepatocellular Carcinoma Promotes Stronger Binding of the HNF‑4α Transcription Factor."
8.	GlucokinaseIBA 06/01/2023 - "There is an increasing body of literature regarding monogenic diabetes, particularly the more common forms of glucokinase and HNF1-alpha mutations (MODY2 and MODY3). " 06/01/2004 - "Most affected patients harbour mutations in either GCK (encoding glucokinase, also called MODY2) and HNF1A (encoding hepatic nuclear factor-1alpha, also called MODY3). " 05/01/2005 - "Forty families with a clinical presentation suggestive of MODY were screened for the most common MODY subtypes caused by mutations in the genes encoding glucokinase (GCK, MODY2) and hepatocyte nuclear 1-alpha (HNF1A/TCF1, MODY3). " 01/15/2005 - "A total of 45 patients had a mutation in the HNF-1alpha-gene (which is linked to MODY3), 11 in the glucokinase gene (MODY2) and 9 in the HNF-4alpha-gene (MODY1). " 06/01/2001 - "Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1alpha (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. "
9.	Insulin (Novolin)FDA Link 10/01/2023 - "The relative deficiency of serum insulin levels and the normal response to insulin treatment in homozygous mice were markedly similar to those in the MODY3 disorder in humans. " 01/01/2023 - "An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells." 01/01/2021 - "Overall, our findings reveal the importance of HNF1A in regulating GLUT2 and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients." 01/01/2018 - "Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3." 03/01/2015 - "A 12-year-old Japanese girl with MODY3 had been treated with insulin for 6 months since the time of diagnosis. "
10.	Mitochondrial DNA (mtDNA)IBA 07/01/2004 - "The aim of this study was characterization of a family carrying two mutations known to cause monogenic forms of diabetes, the M626K mutation in the HNF1alpha gene (MODY3) and the A3243G in mtDNA. " 03/01/1997 - "Rigorous family studies have identified monogenic subtypes representing 10-15% of all NIDDM: MODY2 related to glucokinase gene mutations, MODY1 and MODY3 secondary to mutation of hepatic nuclear factors, and diabetes resulting from deletion or mutation of mitochondrial DNA. " 09/01/1999 - "Screening for sequence variants in the hepatocyte nuclear factor (HNF)-4alpha (MODY1), glucokinase (MODY2), HNF-1alpha (MODY3) genes and mitochondrial DNA was carried out in 115 Finnish and Swedish patients with early-onset ( </= 40 years) diabetes using the single strand conformation polymorphism (SSCP) technique and direct sequencing. "

Therapies and Procedures

1.	Carbohydrate-Restricted Diet (Low Carbohydrate Diet) 01/01/2022 - "Lifestyle modification including a low-carbohydrate diet should be the first-line treatment for MODY1 and MODY3. "
2.	Therapeutics 02/26/2022 - "This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy." 01/01/2014 - "A family with a novel termination mutation in hepatic nuclear factor 1α in maturity-onset diabetes of the young type 3 which is unresponsive to sulphonylurea therapy." 11/01/2013 - "Potential therapeutics aimed at counteracting functional HNF1α depletion in diabetes and MODY3 will thus have ACE2 induction in pancreatic islets as a likely beneficial effect. " 01/01/2023 - "Although MODY3 is known to respond markedly to sulfonylureas (SU), many cases require insulin therapy. " 12/01/2002 - "Surprisingly, MODY3 patients exhibit hypersensitivity to the hypoglycemic actions of sulfonylurea therapy. "
3.	Glycemic Control 01/01/2023 - "The management of MODY3, even though they have the same single-gene mutation and similar residual insulin secretion at diagnosis, should be flexibly individualized for each family member to ensure long-term adherence and appropriate glycemic control." 03/01/2019 - "Molecular diagnosis of MODY3/1 did transform management in clinical practice and facilitated the glycemic control." 08/01/2011 - "All patients with MODY3 had been diagnosed before age 25 years and required drug therapy for blood glucose control. " 03/01/2015 - "Three years of liraglutide treatment offers continuously optimal glycemic control in a pediatric patient with maturity-onset diabetes of the young type 3."
4.	Fontan Procedure (Fontan Operation) 01/01/2023 - "HCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. "
5.	Pancreas Transplantation 05/01/2012 - "Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience."