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Gene Affects Response to Widely Used Diabetes Drugs

By Cheryl Simon Silver

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Many people with type 2 diabetes must resort to insulin injections when widely prescribed drugs known as sulfonylureas lose their effectiveness and an individual’s blood sugar levels rise. Now, a team of researchers reports that many of these individuals possess a genetic variation that may predispose them to having these drugs fail.

“Diabetics with this genetic variation are twice as likely to require insulin at any point in their life” as diabetics without the variation, says lead researcher Giorgio Sesti of University Magna Graecia of Catanzaro, Italy.

The finding, if confirmed by more studies, may one day help doctors select drugs to control blood-sugar levels in individuals who have the gene variant, possibly helping them to delay or avoid insulin injections. Insulin is seen as the last resort therapy for treating diabetes.

As many as twelve percent of people with type 2 diabetes have the gene variant.

In a large study in the United Kingdom, the U.K. Prospective Diabetes Study, 30 percent of newly diagnosed diabetic patients who were treated with sulfonylureas required insulin within the first six years of therapy.

Sulfonylureas have been used since the 1950s to stimulate beta cells to produce more insulin and have allowed many people with type 2 diabetes to avoid or postpone insulin injections.

Sesti says that individuals who have the gene variant may respond differently to one or another of the drugs in the sulfonylurea group, and that he plans to explore this in another study.

Future studies will also explore whether drugs from other drug groups might enable diabetic individuals with the gene variant, technically known as the Arg972 variant in insulin Receptor substrate-1, to delay or avoid using insulin.

The study, published in Diabetes Care, included 477 Caucasian type 2 diabetics whose illness began when they were 35 years or older. At present a DNA test for the variant is not commercially available in the United States or Italy.

Sesti, G. et al. The Arg972 Variant in Insulin Receptor Substrate-1 is Associated with an Increased Risk of Secondary Failure to Sulfonylurea in Patients with Type 2 Diabetes. Diabetes Care 27, 1394-1398 (June 6, 2004).

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