Defining the genetic aetiology of monogenic diabetes can improve treatment

Abstract

A molecular genetic diagnosis is now possible for > 80% of patients with monogenic diabetes. This not only provides accurate information regarding inheritance and prognosis, but can inform treatment decisions and improve clinical outcome. Mild fasting hyperglycaemia caused by heterozygous GCK mutations rarely requires pharmacological intervention, whereas patients with mutations in the genes encoding the transcription factors HNF-1α and HNF-4α respond well to low doses of sulphonylureas. The recent discovery that mutations in the KCNJ11 gene (encoding the Kir6.2 subunit of the K_ATP channel) are the most common cause of permanent neonatal diabetes, has enabled children to stop insulin injections and achieve improved glycaemic control with high doses of sulphonylurea tablets. Molecular genetic testing is an essential prerequisite for the pharmacogenetic treatment of monogenic diabetes.

Keywords::

• diabetes
• glucokinase
• insulin
• Kir6.2
• maturity-onset diabetes of the young
• monogenic
• neonatal diabetes
• sulphonylureas

Acknowledgements

AL Gloyn is a Diabetes UK RD Lawrence Research Fellow. S Ellard acknowledges the financial support provided by the Research and Development Directorate at the Royal Devon and Exeter NHS Foundation Trust. The authors would like to thank their colleagues in Exeter who have contributed significantly to this work. The authors also thank K Owen for the use of Figure 2.

Notes