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, 57 (1), 54-6

Cross-sectional and Longitudinal Studies Suggest Pharmacological Treatment Used in Patients With Glucokinase Mutations Does Not Alter Glycaemia

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Cross-sectional and Longitudinal Studies Suggest Pharmacological Treatment Used in Patients With Glucokinase Mutations Does Not Alter Glycaemia

Amanda Stride et al. Diabetologia.

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.

Figures

Fig. 1
Fig. 1
Bar chart of mean HbA1c for patients with GCK-MODY treated with either OHAs (n = 6) or insulin (n = 10). Black columns represent HbA1c during treatment and white columns represent HbA1c once treatment had stopped. Error bars represent 95% CIs. To convert values for HbA1c in mmol/mol into %, add 2.15 and divide by 10.929 or use the conversion calculator at www.hba1c.nu/eng/

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References

    1. Hattersley AT, Turner RC, Permutt MA, et al. Linkage of type 2 diabetes to the glucokinase gene. Lancet. 1992;339:1307–1310. doi: 10.1016/0140-6736(92)91958-B. - DOI - PubMed
    1. Stride A, Vaxillaire M, Tuomi T, et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia. 2002;45:427–435. doi: 10.1007/s00125-001-0770-9. - DOI - PubMed
    1. Byrne MM, Sturis J, Clement K, et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest. 1994;93:1120–1130. doi: 10.1172/JCI117064. - DOI - PMC - PubMed
    1. Feigerlova E, Pruhova S, Dittertova L, et al. Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents. Eur J Pediatr. 2006;165:446–452. doi: 10.1007/s00431-006-0106-3. - DOI - PubMed
    1. Steele AM, Wensley KJ, Ellard S, et al. Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies. PLoS One. 2013;8:e65326. doi: 10.1371/journal.pone.0065326. - DOI - PMC - PubMed

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