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

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• 作者：Amanda Stride (1)
  Beverley Shields (2)
  Olivia Gill-Carey (2)
  Ali J. Chakera (2)
  Kevin Colclough (3)
  Sian Ellard (2) (3)
  Andrew T. Hattersley (1) (2)
  
• 关键词：GCK mutation ; Glucokinase ; MODY ; Pharmacogenetics ; Treatment
• 刊名：Diabetologia
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：57
• 期：1
• 页码：54-56
• 全文大小：
• 作者单位：Amanda Stride (1)
  Beverley Shields (2)
  Olivia Gill-Carey (2)
  Ali J. Chakera (2)
  Kevin Colclough (3)
  Sian Ellard (2) (3)
  Andrew T. Hattersley (1) (2)
  
  1. MacLeod Diabetes and Endocrine Centre, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  2. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK
  3. Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  
• ISSN：1432-0428

文摘

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.