Applications of pharmacogenetics: importance in the treatment of diabetes

Editor – It is with interest that I read the recent article by Munir Pirmohamed (Clin Med October 2009 pp 493–5). The article explained how genotype testing might guide drug choice. I would like to highlight how detection of individual gene mutations is being used to influence drug therapy within the specialty of diabetes.

The realisation that some forms of diabetes occur as a result of monogenic mutations has allowed clinicians to optimise patient therapy by choosing drugs that are more likely to overcome the consequences of particular mutations.

Mature Onset Diabetes of the Young (MODY) is an inherited form of diabetes that often presents before the age of 25 years. Identification of genes causing MODY has allowed alternatives to insulin treatment to be offered to patients. Hepatocyte nuclear factor 1 (HNF-1) and glucokinase mutations are the most common causes of MODY.¹ HNF-1α diabetes has a marked sensitivity to sulphonylureas, to the extent that patients can have improved diabetes control with a switch from insulin treatment to sulphonylurea therapy if the mutation is identified. Patients with MODY due to heterozygous glucokinase mutations often do not require insulin treatment at all and may be able to come off treatment altogether.

Permanent neonatal diabetes is a non-autoimmune condition that usually presents before the age of 18 months. It can be caused by monogenic mutations in the KCNJ11 and ABCC8 genes that encode constituents of the -cell KATP channel. Detection of these mutations allows clinicians to offer treatment with sulphonylureas, which act directly on the KATP channel in an attempt to overcome the clinical effects of the mutation. This allows a more readily administered oral treatment with improved disease control in neonates.^2,3

The specialty of diabetes has had the good fortune to be able to provide concrete examples of how detection of genetic mutations might influence drug choice in small subgroups of patients; it must be hoped that the application of pharmacogenetics will become more widespread within all areas of medicine to allow improved patient care in the near future.

• © 2010 Royal College of Physicians