1720-P: The rs10423928 GIP Receptor “A” Allele Contributes to an Improved ß-Cell Response in Prediabetes Patients

Abstract

The gut hormone GIP has become a novel target for T2DM and obesity research due to its glucose-dependent insulinotropic effect. GIP-receptor is therefore a biologically plausible candidate for T2DM treatment. A meta-analysis of genome-wide association studies identified a genetic variant in intron 12 of GIPR (rs10423928, A-allele) that is linked to impaired glucose metabolism. The aim of this study was to investigate the relationship between “A” allele carriers and T2DM susceptibility. Glucose challenge data of 424 prediabetes subjects was analyzed. Genotyping was performed using TaqMan™ SNP Genotyping Assay rs10423928. We extended previous data by showing that carriers of the A allele displayed increased fasting glucose. Unexpectedly, A carriers showed lower glucose levels 2 h after an oral glucose challenge and higher insulin sensitivity (assessed by Cederholm Index) compared to homozygous subjects for the T allele, indicating an enhanced ß-cell response. Furthermore, we found no link between rs10423928 variant and liver fat, total adipose tissue and visceral adipose tissue determined by MRI. Longitudinally, the SNP did not determine responses to dietary supplementation of oat fibers or low-fat vs. low-carb diets. The results suggest a partially advantageous effect of the minor allele A. Further investigation of the role of this gene, along with other SNPs in linkage with rs10423928 is required in larger study groups. Disclosure R. Barbosa-Yañez: None. U. Dambeck: None. C. Honsek: None. S. Kabisch: Research Support; Self; California Walnut Commission, Institute for Grain Processing, Nuthetal, J. Rettenmaier Söhne, Südzucker / Beneo. Other Relationship; Self; Berlin-Chemie AG, Sanofi. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. Funding German Center for Diabetes Research