Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

2.50
Hdl Handle:
http://hdl.handle.net/11287/594015
Title:
Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation
Authors:
Chakera, Ali J.; Steele, A. M.; Gloyn, A. L.; Shepherd, Maggie ( 0000-0003-2660-0955 ) ; Shields, Beverley M; Ellard, Sian ( 0000-0002-7620-5526 ) ; Hattersley, Andrew T.
Abstract:
Glucokinase-maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in approximately 1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10-60%): persistent incidental childhood hyperglycemia (10-60%) and gestational diabetes mellitus (1-2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.
Citation:
Diabetes Care. 2015 Jul;38(7):1383-92.
Publisher:
Diabetes Care
Journal:
Diabetes care
Issue Date:
Jul-2015
URI:
http://hdl.handle.net/11287/594015
DOI:
10.2337/dc14-2769
PubMed ID:
26106223
Additional Links:
http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26106223
Type:
Journal Article; Research Support, Non-U.S. Gov't; Review
Language:
eng
ISSN:
1935-5548
Appears in Collections:
2015 RD&E publications; Diabetes/Endocrine Services; Molecular Genetics; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorChakera, Ali J.en
dc.contributor.authorSteele, A. M.en
dc.contributor.authorGloyn, A. L.en
dc.contributor.authorShepherd, Maggieen
dc.contributor.authorShields, Beverley Men
dc.contributor.authorEllard, Sianen
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2016-01-19T12:38:36Zen
dc.date.available2016-01-19T12:38:36Zen
dc.date.issued2015-07en
dc.identifier.citationDiabetes Care. 2015 Jul;38(7):1383-92.en
dc.identifier.issn1935-5548en
dc.identifier.pmid26106223en
dc.identifier.doi10.2337/dc14-2769en
dc.identifier.urihttp://hdl.handle.net/11287/594015en
dc.description.abstractGlucokinase-maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in approximately 1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10-60%): persistent incidental childhood hyperglycemia (10-60%) and gestational diabetes mellitus (1-2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.en
dc.language.isoengen
dc.publisherDiabetes Careen
dc.relation.urlhttp://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26106223en
dc.titleRecognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutationen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.typeReviewen
dc.identifier.journalDiabetes careen

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