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Glucokinase MODY and Implications for Treatment Goals of Common Forms of Diabetes

  • Genetics (AP Morris, Section Editor)
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Abstract

Treatment goals in diabetes concentrate on reducing the risk of vascular complications, largely through setting targets for glycated haemoglobin (HbA1c). These targets are based on epidemiological studies of complication development, but so far have not adequately addressed the adverse effects associated with lowering HbA1c towards the normal range. Glucokinase (GCK) mutations cause a monogenic form of hyperglycaemia (GCK-MODY) characterised by fasting hyperglycaemia with low postprandial glucose excursions and a marginally elevated HbA1c. Minimal levels of vascular complications (comparable with nondiabetic individuals) are observed in GCK-MODY, leading to the hypothesis that GCK-MODY may represent a useful paradigm for assessing treatment goals in all forms of diabetes. In this review, we discuss the evidence behind this concept, suggest ways of translating this hypothesis into clinical practice and address some of the caveats of such an approach.

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Compliance with Ethics Guidelines

Conflict of Interest

Ramzi A. Ajjan received research support from the NIHR, BHF, Sir Jules Thorn Trust, Abbott, Bayer, Eli Lilly, LifeScan, NovoNordisk and Takeda. He also received Advisory Board and Speaker's honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Glaxo SmithKline, Merck Sharpe & Dohme, NovoNordisk, Roche and Takeda.

Katharine R. Owen has received research support through grants from the National Institute for Health Research (NIHR), the European Foundation for the Study of Diabetes (EFSD), and Diabetes UK and has received speaker’s honoraria from Diabetes UK and Sanofi.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. LIGHT Laboratories, University of Leeds, Leeds, UK

    Ramzi A. Ajjan

  2. Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK

    Ramzi A. Ajjan

  3. Oxford Centre for Diabetes Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    Katharine R. Owen

  4. Oxford NIHR Biomedical Research Centre, Oxford, UK

    Katharine R. Owen

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  1. Ramzi A. Ajjan
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  2. Katharine R. Owen
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Correspondence to Katharine R. Owen.

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This article is part of the Topical Collection on Genetics

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Ajjan, R.A., Owen, K.R. Glucokinase MODY and Implications for Treatment Goals of Common Forms of Diabetes. Curr Diab Rep 14, 559 (2014). https://doi.org/10.1007/s11892-014-0559-0

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  • DOI: https://doi.org/10.1007/s11892-014-0559-0

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