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Gene Variant Linked to Insulin Resistance in Diabetes

Most of the other 18 linked loci are associated with impaired beta cell function

THURSDAY, Sept. 10 (HealthDay News) -- A gene variant associated with type 2 diabetes is unusual among previously linked loci in being associated with insulin resistance and hyperinsulinemia, rather than impaired pancreatic beta cell function, according to a study published online Sept. 6 in Nature Genetics.

Johan Rung, from McGill University in Montreal, and colleagues performed a genome-wide association study of 392,365 single nucleotide polymorphisms (SNPs) in 1,376 French individuals (679 type 2 diabetics and 697 controls). The 16,360 SNPs associated with the disease were tested in an independent group of 4,977 French individuals, and the top 28 SNPs were tested in 7,698 Danish subjects.

The researchers identified four SNPs strongly associated with type 2 diabetes. One of the SNPs (rs2943641, odds ratio 1.19) was located next to the insulin receptor substrate 1 gene (IRS1). The C allele of this SNP was not associated with beta cell dysfunction, which is mostly the case for the 18 type 2 diabetes loci identified so far, and instead was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish, and Finnish subjects.

"Taken together, these results show that the C allele of rs2943641 near IRS1 is associated with increased type 2 diabetes risk, fasting- and glucose-stimulated hyperinsulinemia and impaired insulin sensitivity," Rung and colleagues conclude.

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