Findings from National Institute of Diabetes and Digestive and Kidney Disease advance knowledge in type 2 diabetes

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March 16th, 2009

   2009 MAR 16 -- According to recent research from the United States, "In recent genome-wide association studies, variants in CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, CDKN2B, LOC387761, and FTO were associated with risk for type 2 diabetes in Caucasians. We investigated the association of these single nucleotide polymorphisms (SNPs) and some additional tag SNPs with type 2 diabetes and related quantitative traits in Pima Indians."

   "Forty-seven SNPs were genotyped in 3,501 Pima Indians informative for type 2 diabetes and BMI, among whom 370 had measures of quantitative traits. FTO provided the strongest evidence for replication, where SNPs were associated with type 2 diabetes (odds ratio = 1.20 per copy of the risk allele, P = 0.03) and BMI (P = 0.002). None of tire other previously reported SNPs were associated with type 2 diabetes; however, associations were found between CDKAL1 and HHEX variants and acute insulin response (AIR), where the Caucasian risk alleles for type 2 diabetes were associated with reduced insulin secretion in normoglycemic Pima, Indians. Multiallelic analyses of carrying risk alleles for multiple genes showed correlations between number of risk alleles and type 2 diabetes and impaired insulin secretion in normoglycemic subjects (P = 0.006 and 0.0001 for type 2 diabetes and AIR, respectively), supporting the hypothesis that many of these genes influence diabetes risk by affecting insulin secretion. Variation in FTO impacts BMI, but the implicated common variants in the other genes did not confer a significant risk for type 2 diabetes in Pima Indians. However, confidence intervals for their estimated effects were consistent with the small effects reported in Caucasians, and the multiallelic ''genetic risk profile'' identified in Caucasians is associated with diminished early insulin secretion in Pima Indians," wrote R. Rong and colleagues, National Institute of Diabetes and Digestive and Kidney Disease.

   The researchers concluded: "Diabetes 58: 478-488, 2009'."

   Rong and colleagues published their study in Diabetes (Association Analysis of Variation in/Near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B With Type 2 Diabetes and Related Quantitative Traits in Pima Indians. Diabetes, 2009;58(2):478-488).

   For additional information, contact L.J. Baier, National Institute of Diabetes & Digestive & Kidney Diseases, Phoenix Epidemiology & Clinic Research Branch, National Institutes of Health, Phoenix, AZ, USA.

   Publisher contact information for the journal Diabetes is: American Diabetes Association, 1701 N Beauregard St., Alexandria, VA 22311-1717, USA.

   Keywords: United States, Phoenix, Acute Insulin Response, Gastroenterology, Genotyping, Kidney Disease, Non-insulin Dependent Diabetes Mellitus, Type 2 Diabetes Mellitus, National Institute of Diabetes and Digestive and Kidney Disease.

   This article was prepared by Diabetes Week editors from staff and other reports. Copyright 2009, Diabetes Week via NewsRx.com.

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