Defining the genetic aetiology of monogenic diabetes can improve treatment.
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-1alpha and HNF-4alpha 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.
Gloyn
Anna L
AL
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK. anna.gloyn@drl.ox.ac.uk
Ellard
Sian
S
D017668:Age of Onset; D000818:Animals; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism
D007328:Insulin