Permanent Neonatal Diabetes Mellitus

A rare autosomal dominant genetically heterogeneous hereditary form of diabetes mellitus which is distinct from Type I diabetes mellitus and affected individuals present with insulin-requiring hyperglycemia within the first 3 months of life. About 50% of cases resolve by 3 months but may later develop type II diabetes. The cases that do not resolve develop permanent insulin-dependent diabetes and many also have neurologic and morphologic abnormalities. Mutations in the GCK, KCNJ11, ABCC8, and INS genes have been identified. OMIM: 606176

Also Known As:

Networked: 91 relevant articles (3 outcomes, 5 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Type 2 Diabetes Mellitus (MODY)
2.	Mason-Type Diabetes
3.	Hyperglycemia
4.	Diabetes Mellitus
5.	Wolcott-Rallison syndrome

Experts

1.	Hattersley, Andrew T: 9 articles (01/2019 - 12/2004)
2.	Ellard, Sian: 9 articles (03/2014 - 04/2007)
3.	Barbetti, Fabrizio: 6 articles (07/2022 - 01/2005)
4.	Ashcroft, Frances M: 5 articles (08/2013 - 12/2004)
5.	Gloyn, Anna L: 5 articles (07/2008 - 12/2004)
6.	Hussain, Khalid: 4 articles (01/2022 - 03/2010)
7.	Malecki, Maciej T: 4 articles (08/2013 - 01/2006)
8.	Iafusco, Dario: 3 articles (07/2022 - 01/2005)
9.	Renner, Simone: 3 articles (01/2021 - 05/2013)
10.	Wolf, Eckhard: 3 articles (01/2021 - 05/2013)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Permanent Neonatal Diabetes Mellitus:

1.	Insulin (Novolin)FDA Link 12/01/2017 - "She showed no remission of diabetes and has hitherto been reliant on insulin (now aged of 5.5 years), which supports a diagnosis of permanent neonatal diabetes mellitus. " 05/01/2020 - "The present study aimed to evaluate the genetic variants in the insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations. " 01/01/1975 - "Permanent neonatal diabetes mellitus: a case report with plasma insulin studies." 01/10/2023 - "[Clinical and genetic analysis of an infant with permanent neonatal diabetes mellitus due to novel variant of insulin gene]." 07/01/2022 - "Though limited to a single patient with pancreas agenesis we believe that the use of pump should be warranted in patients with permanent neonatal diabetes mellitus and intestinal malabsorption, even with undiluted insulin."
2.	Glyburide (Glibenclamide)FDA LinkGeneric 07/01/2016 - "Development and stability study of glibenclamide oral liquid paediatric formulations for the treatment of permanent neonatal diabetes mellitus." 11/01/2008 - "Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene." 11/01/2004 - "Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2." 09/01/2013 - "Changing the Treatment of Permanent Neonatal Diabetes Mellitus from Insulin to Glibenclamide in a 4-Month-Old Infant with KCNJ11 Activating Mutation." 03/01/2010 - "We describe a 3-year-old girl with permanent neonatal diabetes mellitus with a mutation in the KCNJ11 gene (R201H), who was successfully transferred from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control. "
3.	GlucokinaseIBA 12/09/2021 - "Author Correction: Generation of permanent neonatal diabetes mellitus dogs with glucokinase point mutations through base editing." 10/12/2021 - "Generation of permanent neonatal diabetes mellitus dogs with glucokinase point mutations through base editing." 01/01/2020 - "Herein, we present the case of a male child with permanent neonatal diabetes mellitus whose mutational analysis revealed a novel homozygous deletion mutation in the glucokinase gene. " 01/01/2020 - "However, homozygous or compound heterozygous mutations in the glucokinase gene are a rare cause of permanent neonatal diabetes mellitus. " 01/01/2020 - "A family with novel homozygous deletion mutation (c.1255delT; p.Phe419Serfs*12) in the glucokinase gene, which is a rare cause of permanent neonatal diabetes mellitus."
4.	Urea (Carbamide)FDA LinkGeneric 10/01/2012 - "To contribute to the understanding of experimental pharmacology and therapeutics of GKAs, we have tested the efficacy of one of these agents (Piragliatin) in isolated islets from humans with type 2 diabetes mellitus (T2DM), from mice with glucokinase (GK) mutations induced by ethyl-nitroso-urea (ENU) as models of Maturity Onset Diabetes of the Young linked to GK and Permanent Neonatal Diabetes Mellitus linked to GK (PNDM-GK) and finally of islets rendered glucose insensitive by treatment with the sulphonyl urea compound glyburide in organ culture. "
5.	Glucose (Dextrose)FDA LinkGeneric 10/01/2012 - "To contribute to the understanding of experimental pharmacology and therapeutics of GKAs, we have tested the efficacy of one of these agents (Piragliatin) in isolated islets from humans with type 2 diabetes mellitus (T2DM), from mice with glucokinase (GK) mutations induced by ethyl-nitroso-urea (ENU) as models of Maturity Onset Diabetes of the Young linked to GK and Permanent Neonatal Diabetes Mellitus linked to GK (PNDM-GK) and finally of islets rendered glucose insensitive by treatment with the sulphonyl urea compound glyburide in organ culture. "
6.	piragliatinIBA 10/01/2012 - "To contribute to the understanding of experimental pharmacology and therapeutics of GKAs, we have tested the efficacy of one of these agents (Piragliatin) in isolated islets from humans with type 2 diabetes mellitus (T2DM), from mice with glucokinase (GK) mutations induced by ethyl-nitroso-urea (ENU) as models of Maturity Onset Diabetes of the Young linked to GK and Permanent Neonatal Diabetes Mellitus linked to GK (PNDM-GK) and finally of islets rendered glucose insensitive by treatment with the sulphonyl urea compound glyburide in organ culture. "
7.	KATP ChannelsIBA 01/01/2007 - "Several studies have reported activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic KATP channel, in patients with permanent neonatal diabetes mellitus for 30-50% of the cases. " 01/01/2021 - "Activating or gain of function mutations of KATP channel genes namely KCNJ11 and ABCC8 are most predominant cause of permanent neonatal diabetes mellitus (PNDM). " 09/01/2018 - "Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel (KATP) subunits. " 06/01/2017 - "Permanent neonatal diabetes mellitus (PNDM) is caused by mutations in the ATP-sensitive potassium channel (KATP channel) subunits. " 12/01/2014 - "Permanent Neonatal Diabetes Mellitus (PNDM), is a rare monogenic disorder, caused by activating mutations of the KATP channel. "
8.	ProteomeIBA 01/01/2020 - "Our study provides novel insights into proteome changes in neutrophils from a large animal model for permanent neonatal diabetes mellitus and points to dysregulation of neutrophil function even in an early stage of this disease. "
9.	TabletsIBA 07/01/2016 - "To develop and study the physicochemical and microbiological stability of two liquid glibenclamide formulations for the treatment of permanent neonatal diabetes mellitus: two suspensions (2.5 mg/mL)-one using glibenclamide raw material and the other, glibenclamide tablets. "
10.	SuspensionsIBA 07/01/2016 - "To develop and study the physicochemical and microbiological stability of two liquid glibenclamide formulations for the treatment of permanent neonatal diabetes mellitus: two suspensions (2.5 mg/mL)-one using glibenclamide raw material and the other, glibenclamide tablets. "

Therapies and Procedures

1.	Therapeutics 01/01/2014 - "Permanent neonatal diabetes mellitus in monozygotic twins achieving low-dose sulfonylurea therapy." 12/01/2013 - "Permanent neonatal diabetes mellitus requires lifelong therapy, whereas transient form resolves early in life but may relapse later on. " 06/01/2012 - "Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up." 01/01/2018 - "We aimed to compare sulfonylurea therapy with insulin treatment in two sulfonylurea-sensitive individuals with a KCNJ11 mutation who had poorly controlled permanent neonatal diabetes mellitus. " 01/01/2018 - "Sulfonylurea vs insulin therapy in individuals with sulfonylurea-sensitive permanent neonatal diabetes mellitus, attributable to a KCNJ11 mutation, and poor glycaemic control."
2.	Glycemic Control 01/01/2013 - "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene. " 01/01/2013 - "Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (NDM), and successful glycemic control has been obtained in several cases with oral sulfonylureas (SU). " 06/01/2012 - "Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up." 03/01/2010 - "We describe a 3-year-old girl with permanent neonatal diabetes mellitus with a mutation in the KCNJ11 gene (R201H), who was successfully transferred from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control. "
3.	Precision Medicine 03/01/2012 - "Personalized medicine switching from insulin to sulfonylurea in permanent neonatal diabetes mellitus dictated by a novel activating ABCC8 mutation."
4.	Injections 01/01/2017 - "The most common genetic cause of permanent neonatal diabetes mellitus is activating mutations in KCNJ11, which can usually be treated using oral sulfonylureas (SUs) instead of insulin injections, although some mutations are SU unresponsive. "