Endocrine Abstracts

Type 2 diabetes (T2DM) patients are at high risk for vascular complications. Some of them have even a higher risk during metformin therapy, as we have recently shown by associations of polymorphisms in the Oct1 gene with a therapy-dependent increased risk of cardiovascular death. In this study, we investigated whether Oct1 gene variants were associated with cardiovascular characteristics such as pulse wave velocity (PWV), echocardiographic parameters and intima/media thickness (IMT) in non-diabetic, prediabetic and T2DM patients at cardiovascular risk. Data from the BioPersMed cohort (n=1025), a prospective cohort study of asymptomatic patients at cardiovascular risk, were analysed. T2DM, prediabetes and absence of diabetes (non-diabetics) were defined according to ADA criteria. Determination of Oct1 genotypes was done by GSA array (Illumina Inc., USA), pulse wave analysis by a SphygmoCor device (Atcor Medical, Australia), and carotid intima/media thickness as well as echocardiographic measurements were performed using the Vivid 9 device (GE Healthcare Austria GmbH & Co OG, Austria). In a preliminary analysis, we focused on associations with score systems for cardiovascular risk (PROCAM and Framingham), as well as PWV and IMT. An association with the Framingham score was found for SNPs rs35888596 (P=0.012) and for rs112476023 (P=0.015) in nondiabetics and for rs461473 (P=0.018) and rs806383 (P=0.03) in prediabetics. PROCAM score was associated in non-diabetics with rs112476023 (P=0.023) and in T2DM with rs662138 (P=0.045). A significant association with PWV was seen for rs12208357 (P=0.02) in non-diabetics, for rs12208357 (P=0.009) in prediabetics and for rs662138 (P=0.034) in T2DM. Associations with IMT were documented in T2DM for rs806383 (P=0.034), rs2197296 (P=0.027), rs622342 (P=0.008), as well as for rs662138 (P=0.030), in prediabetics for rs34130495 (P=0.048) and rs622342 (P=0.049) and in T2DM for rs2282142 (P=0.008), rs2282143 (P=0.009) and rs112476023 (P=0.019). According to these associations, several variants in the OCT1 gene might play a consistent role in the modulation of vascular properties and concomitant cardiovascular characteristics and thus contribute to an increased cardiovascular risk even beyond the occurrence of diabetes or therapy options.