ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

Ovsyannikova, Alla; Rymar, O. D.; Shakhtshneider, E.; Климонтов, Вадим Валерьевич; Koroleva, Elena A.; Myakina, Natalya Evgenyevna; Воевода, М. И.

doi:10.1007/s13300-016-0192-9

Cited by 48 publications

(50 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is also interesting that two offspring developed GAD antibody‐positive insulin‐dependent diabetes at age 2 years of age and 9 months, respectively, and both tested negative for the ABCC8 mutation. Several factors may explain the variability in phenotype seen within families, such as the type and location of the mutation itself or other genetic modifiers and superimposed environmental factors .…”

Section: Discussionmentioning

confidence: 99%

“…A similar case was reported by Ovsyannikova et al . , where the person was diagnosed with type 1 diabetes at age 27 years (p.Ala1457Thr mutations in ABCC8 ) and at initial investigation he had non‐proliferative retinopathy and a raised microalbumin‐creatinine ratio. Four months later he developed pre‐proliferative retinopathy and macular oedema of both eyes, requiring pan retinal laser photocoagulation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

et al. 2019

View full text Add to dashboard Cite

Aims To examine the phenotypic features of people identified with ABCC8-maturity-onset diabetes of the young (MODY) who were included in the adult 'Mater MODY' cohort and to establish their response to sulfonylurea therapy. Methods Ten participants with activating ABCC8 mutations were phenotyped in detail. A 2-hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C-peptide measurements taken at baseline and 30-min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8-MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea. ResultsThe mean age at diagnosis of diabetes was 33.8 AE 11.1 years, with fasting glucose of 18.9 AE 11.5 mmol/l and a mean (range) HbA 1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8-MODY three out of four participants discontinued insulin (mean duration 10.6 AE 1.69 years) and started sulfonylurea treatment. The mean (range) HbA 1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post-treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants.Conclusions Low-dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…We analyzed six novel K ATP channel variants as possible pathogenic dominant HI mutations by clinical phenotyping of carrier parents and by in vitro expression studies. Five of these mutations were novel and one had previously been reported both as a dominant and a recessive defect ( ABCC8 : p.Ala1458Thr; Huopio et al, ; Macmullen et al, ; Ovsyannikova et al, ; Reimann et al, ). As shown in Table , three of the novel mutations were in ABCC8 and three in KCNJ11 .…”

Section: Resultsmentioning

confidence: 98%

Novel dominant K_ATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping

Boodhansingh

Balamurugan

Mitteer

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Inactivating mutations in the genes encoding the two subunits of the pancreatic beta‐cell KATP channel, ABCC8 and KCNJ11, are the most common finding in children with congenital hyperinsulinism (HI). Interpreting novel missense variants in these genes is problematic, because they can be either dominant or recessive mutations, benign polymorphisms, or diabetes mutations. This report describes six novel missense variants in ABCC8 and KCNJ11 that were identified in 11 probands with congenital HI. One of the three ABCC8 mutations (p.Ala1458Thr) and all three KCNJ11 mutations were associated with responsiveness to diazoxide. Sixteen family members carried the ABCC8 or KCNJ11 mutations; only two had hypoglycemia detected at birth and four others reported symptoms of hypoglycemia. Phenotype testing of seven adult mutation carriers revealed abnormal protein‐induced hypoglycemia in all; fasting hypoketotic hypoglycemia was demonstrated in four of the seven. All of six mutations were confirmed to cause dominant pathogenic defects based on in vitro expression studies in COSm6 cells demonstrating normal trafficking, but reduced responses to MgADP and diazoxide. These results indicate a combination of in vitro and in vivo phenotype tests can be used to differentiate dominant from recessive KATP channel HI mutations and personalize management of children with congenital HI.

show abstract

“…Because gliflozins (sodium glucose cotransporter‐2 inhibitors) have a mechanism of action that is independent on insulin, they could be used (preferably in combination therapy) in transcription factor‐linked MODY patients. In the case of a young patient with ATP‐binding cassette transporters, subfamily C, member 8‐related MODY (MODY 12), with advanced microvascular complications (retinopathy) and poor glycaemic control during gliclazide therapy, improved glycaemic control without hypoglycaemia was described after dapagliflozin had been added …”

Section: Treatment Of Different Types Of Modymentioning

confidence: 99%

“…In the case of a young patient with ATP-binding cassette transporters, subfamily C, member 8-related MODY (MODY 12), with advanced microvascular complications (retinopathy) and poor glycaemic control during gliclazide therapy, improved glycaemic control without hypoglycaemia was described after dapagliflozin had been added. 50 2.2.6 | Therapy of the most common transcription factorlinked maturity-onset diabetes of the young patients during pregnancy…”

Section: Gliflozinsmentioning

confidence: 99%

Use of oral antidiabetic drugs in the treatment of maturity‐onset diabetes of the young: A mini review

Brunerová

Rahelić

Ceriello

et al. 2017

Diabetes Metabolism Res

View full text Add to dashboard Cite

SummaryMODY (maturity-onset diabetes of the young) is a genetically linked group of clinically heterogeneous subtypes of diabetes. Roughly 5% of people with diabetes mellitus diagnosed prior to age 45 have MODY diabetes. Most of them have been erroneously diagnosed as patients with either type 1 or type 2 diabetes and, as a result, have been improperly treated. Genetic identification of MODY diabetes and its subtypes allows proper treatment and enables clinicians to switch many patients to oral antidiabetic agents, mainly sulphonylureas. However, some new classes of oral antidiabetic drugs have also been tested and found to be effective in MODY patients. We have searched for research articles and case reports written in full-text English or with an English abstract, using the following keywords: MODY and oral antidiabetic* in the databases Cochrane Library, PubMed, and Science Direct. Therapeutic options using currently standardized oral anti-

show abstract

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

Cited by 48 publications

References 25 publications

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

Novel dominant K_ATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping

Use of oral antidiabetic drugs in the treatment of maturity‐onset diabetes of the young: A mini review

Contact Info

Product

Resources

About

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

Cited by 48 publications

References 25 publications

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy

Novel dominant KATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping

Use of oral antidiabetic drugs in the treatment of maturity‐onset diabetes of the young: A mini review

Contact Info

Product

Resources

About

Novel dominant K_ATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping