323-OR: Associations of Leukocyte Telomere Length and Related Allelic Variations with the Risk of Coronary Events in People with Long-Standing Type 1 Diabetes

Abstract

Backgrounds and Aims: Leukocyte telomere length (LTL) is associated with cardiovascular risk. We evaluated associations between LTL, allelic variations (SNPs) in LTL-related genes (associated with LTL in the literature) and the incidence of coronary artery disease (CAD) in adults with long-standing type 1 diabetes. Participants and Methods: LTL was measured by real-time PCR in 260 participants of the GENEDIAB cohort (males 60%, age 45±12 years, duration of diabetes 29±years at baseline, mean±SD) . Thirty-three SNPs in LTL-associated genes were genotyped in 826 participants from GENEDIAB and GENESIS cohorts (males 55%, age 43±12 years, duration of diabetes 27±9 years at baseline) . The risk for CAD (myocardial infarction or coronary artery revascularization) during follow-up was analyzed using Cox models according to LTL (expressed in tertiles of distribution) and SNPs. Results: The cumulative incidence of CAD in GENEDIAB (11±7-year follow-up) was 21.2%. The incidence of CAD by LTL tertiles was 27.6% (shorter LTL) , 23.3% (intermediate LTL) and 12.6% (longer LTL) . Hazard ratio (HR) for shorter vs. longer LTL was 1.63 (95%CI 1.15-2.37) , p=0.005, unadjusted model, and 1.58 (95%CI 1.08-2.39) , p=0.02, after adjustment on sex, age, duration of diabetes, blood pressure, kidney function and history of CAD at baseline. The cumulative incidence of CAD in GENEDIAB and GENESIS pooled data (followed by 11±6 years) was 15.1%. Six SNPs located in three genes (TERC, NAF1 and TNKS) were significantly associated with the incidence of CAD. Discussion: Shorter LTL at baseline was associated with an increased risk of CAD during the follow-up in adults with long-standing type 1 diabetes. Allelic variations in LTL-related genes were also associated with coronary risk in these subjects. Disclosure M.Sanchez: None. G.Velho: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi. N.Venteclef: None. F.Fumeron: None. A.Scheen: Advisory Panel; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. J.Gautier: Other Relationship; Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company. M.Marre: Board Member; AstraZeneca, Consultant; Novo Nordisk. R.Roussel: None. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca.