Type 2 diabetes is an increasing health burden with over 150,000,000 people affected worldwide. Control of blood glucose is the main therapeutic goal for people with type 2 (non-insulin dependent) diabetes. Most patients on drug treatment receive sulphonylurea drugs, or metformin, or both. Guidelines for treatment assume that all patients with diabetes respond similarly to treatment. No previous studies have assessed whether different causes of diabetes change the response to oral hypoglycaemic therapy.

A genetic sub-type of diabetes is caused by mutations in the hepatocyte nuclear factor-1alpha (HNF-1 a) gene. Ewan Pearson and Andrew Hattersley from the Peninsular Medical School, Exeter, UK, and colleagues assessed whether the glycaemic response to the sulphonylurea gliclazide and the biguanide metformin differed among patients with HNF-1a type 2 diabetes and patients with type 2 diabetes where there was not a defined cause.

Patients from both groups had a similar degree of obesity and similar blood glucose concentrations. Those patients with HNF-1a type 2 diabetes had around a fivefold greater response to gliclazide than to metformin while patients without a defined cause for their type 2 diabetes responded similarly to the two treatments. The sulphonylurea response in HNF-1a patients was fourfold greater than the response in type 2 diabetes.

Andrew Hattersley comments: "We have shown that the cause of diabetes determines the response to hypoglycaemic drugs; with a genetic subtype of diabetes being very sensitive to the effects of sulphonylureas. This knowledge is crucial in deciding the best treatment for individual patients. The individualisation of patients treatment is an important goal of the major work to define the genetic and environmental causes of
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Contact: Joe Santangelo
j.santangelo@elsevier.com
212-633-3810
Lancet
16-Oct-2003