[en] BACKGROUND: Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes. METHODS: We assessed associations of LTL, measured at baseline by RT-PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes. RESULTS: In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39-7.70), p = 0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04-2.55), p = 0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline. CONCLUSIONS: Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes.
Sanchez, Manuel; INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, Université ; UFR de Médecine, Université Paris Cité, Paris, France. manuel.sanchez@aphp.fr. ; Department of Geriatrics, Assistance Publique - Hôpitaux de Paris, Bichat
Kannengiesser, Caroline; UFR de Médecine, Université Paris Cité, Paris, France. ; Department of Genetics, Assistance Publique - Hôpitaux de Paris, DHU FIRE, Bichat
Hoang, Sophie; Department of Geriatrics, Charles-Foix University Hospital, Vitry sur Seine,
Potier, Louis; INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, Université ; UFR de Médecine, Université Paris Cité, Paris, France. ; Department of Diabetology, Endocrinology and Nutrition, Assistance Publique -
Scheen, André ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques
Gautier, Jean-François; INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, Université ; UFR de Médecine, Université Paris Cité, Paris, France. ; Department of Diabetology, Endocrinology and Nutrition, Assistance Publique -
Hadjadj, Samy; Institut du Thorax, INSERM, CNRS, CHU Nantes, Université de Nantes, Nantes,
Marre, Michel; Clinique Ambroise Paré, Neuilly-sur-Seine, France.
Roussel, Ronan; INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, Université ; UFR de Médecine, Université Paris Cité, Paris, France. ; Department of Diabetology, Endocrinology and Nutrition, Assistance Publique -
Mohammedi, Kamel; INSERM U1034, Bordeaux University and Hospital, Bordeaux, France.
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