Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia

2.50
Hdl Handle:
http://hdl.handle.net/11287/593787
Title:
Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia
Authors:
Stride, A.; Shields, Beverley M; Gill-Carey, O.; Chakera, Ali J.; Colclough, Kevin; Ellard, Sian ( 0000-0002-7620-5526 ) ; Hattersley, Andrew T.
Abstract:
AIMS/HYPOTHESIS: Heterozygous glucokinase (GCK) mutations cause mild, fasting hyperglycaemia from birth. Although patients are usually asymptomatic and have glycaemia within target ranges, some are put on pharmacological treatment. We aimed to investigate how many patients are on pharmacological treatment and the impact of treatment on glycaemic control. METHODS: Treatment details were ascertained for 799 patients with heterozygous GCK mutations. In a separate, longitudinal study, HbA1c was obtained for 16 consecutive patients receiving insulin (n = 10) or oral hypoglycaemic agents (OHAs) (n = 6) whilst on treatment, and again having discontinued treatment following a genetic diagnosis of GCK-MODY. For comparison, HbA1c before and after genetic testing was studied in a control group (n = 18) not receiving pharmacological therapy. RESULTS: At referral for genetic testing, 168/799 (21%) of patients were on pharmacological treatment (13.5% OHAs, 7.5% insulin). There was no difference in the HbA1c of these patients compared with those receiving no treatment(median [IQR]: 48 [43, 51] vs 46 [43, 50] mmol/mol, respectively; 6.5% [6.1%, 6.8%] vs 6.4% [6.1%, 6.7%]; p = 0.11). Following discontinuation of pharmacological treatment in 16 patients, HbA1c did not change. The mean change in HbA1c was -0.68 mmol/mol (95% CI: -2.97, 1.61) (-0.06% [95% CI: -0.27, 0.15]). CONCLUSIONS/INTERPRETATION: Prior to a genetic diagnosis, 21% of patients were on pharmacological treatment. HbA1c was no higher than in untreated patients and did not change when therapy was discontinued, suggesting no impact on glycaemia. The lack of response to pharmacological therapy is likely to reflect the regulated hyperglycaemia seen in these patients owing to their glucose sensing defect and is an example of pharmacogenetics.
Citation:
Diabetologia. 2014 Jan;57(1):54-6.
Publisher:
Springer
Journal:
Diabetologia
Issue Date:
1-Jan-2014
URI:
http://hdl.handle.net/11287/593787
DOI:
10.1007/s00125-013-3075-x
PubMed ID:
24092492
Additional Links:
http://dx.doi.org/10.1007/s00125-013-3075-x
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1432-0428
Appears in Collections:
2014 RD&E publications; Molecular Genetics; Molecular Genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorStride, A.en
dc.contributor.authorShields, Beverley Men
dc.contributor.authorGill-Carey, O.en
dc.contributor.authorChakera, Ali J.en
dc.contributor.authorColclough, Kevinen
dc.contributor.authorEllard, Sianen
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2016-01-19T12:34:55Zen
dc.date.available2016-01-19T12:34:55Zen
dc.date.issued2014-01-01en
dc.identifier.citationDiabetologia. 2014 Jan;57(1):54-6.en
dc.identifier.issn1432-0428en
dc.identifier.pmid24092492en
dc.identifier.doi10.1007/s00125-013-3075-xen
dc.identifier.urihttp://hdl.handle.net/11287/593787en
dc.description.abstractAIMS/HYPOTHESIS: Heterozygous glucokinase (GCK) mutations cause mild, fasting hyperglycaemia from birth. Although patients are usually asymptomatic and have glycaemia within target ranges, some are put on pharmacological treatment. We aimed to investigate how many patients are on pharmacological treatment and the impact of treatment on glycaemic control. METHODS: Treatment details were ascertained for 799 patients with heterozygous GCK mutations. In a separate, longitudinal study, HbA1c was obtained for 16 consecutive patients receiving insulin (n = 10) or oral hypoglycaemic agents (OHAs) (n = 6) whilst on treatment, and again having discontinued treatment following a genetic diagnosis of GCK-MODY. For comparison, HbA1c before and after genetic testing was studied in a control group (n = 18) not receiving pharmacological therapy. RESULTS: At referral for genetic testing, 168/799 (21%) of patients were on pharmacological treatment (13.5% OHAs, 7.5% insulin). There was no difference in the HbA1c of these patients compared with those receiving no treatment(median [IQR]: 48 [43, 51] vs 46 [43, 50] mmol/mol, respectively; 6.5% [6.1%, 6.8%] vs 6.4% [6.1%, 6.7%]; p = 0.11). Following discontinuation of pharmacological treatment in 16 patients, HbA1c did not change. The mean change in HbA1c was -0.68 mmol/mol (95% CI: -2.97, 1.61) (-0.06% [95% CI: -0.27, 0.15]). CONCLUSIONS/INTERPRETATION: Prior to a genetic diagnosis, 21% of patients were on pharmacological treatment. HbA1c was no higher than in untreated patients and did not change when therapy was discontinued, suggesting no impact on glycaemia. The lack of response to pharmacological therapy is likely to reflect the regulated hyperglycaemia seen in these patients owing to their glucose sensing defect and is an example of pharmacogenetics.en
dc.language.isoengen
dc.publisherSpringeren
dc.relation.urlhttp://dx.doi.org/10.1007/s00125-013-3075-xen
dc.titleCross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemiaen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalDiabetologiaen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.