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 KATP 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.