دورية أكاديمية

Leukocyte Telomere Length, DNA Oxidation, and Risk of Lower-Extremity Amputation in Patients With Long-standing Type 1 Diabetes.

التفاصيل البيبلوغرافية
العنوان: Leukocyte Telomere Length, DNA Oxidation, and Risk of Lower-Extremity Amputation in Patients With Long-standing Type 1 Diabetes.
المؤلفون: Sanchez, Manuel1,2,3 manuel.j.sanchez@wanadoo.fr, Hoang, Sophie1, Kannengiesser, Caroline2,4, Potier, Louis1,2,5, Hadjadj, Samy6, Marre, Michel1,5, Roussel, Ronan1,2, Velho, Gilberto1, Mohammedi, Kamel1,7,8
المصدر: Diabetes Care. Apr2020, Vol. 43 Issue 4, p828-834. 7p.
مصطلحات موضوعية: *TYPE 1 diabetes, *DNA adducts, *TELOMERES, *PROPORTIONAL hazards models, *AMPUTATION, *DNA, *LEG surgery, *DNA metabolism, *REACTIVE oxygen species, *CELL division, *COMPARATIVE studies, *LEG, *LEUCOCYTES, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *OXIDATION-reduction reaction, *RESEARCH, *TIME, *EVALUATION research, *DIABETIC foot, *DISEASE incidence, *DISEASE progression, *DISEASE complications
مستخلص: Objective: Telomere shortening and DNA oxidation are associated with premature vascular aging, which may be involved in lower-extremity amputation (LEA). We sought to investigate whether leukocyte telomere length (LTL) and plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation, were associated with LEA in subjects with type 1 diabetes at high vascular risk.Research Design and Methods: LTL (quantitative PCR) and plasma 8-OHdG concentrations (immunoassay method) were assessed at baseline in the GENEDIAB (Génétique de la Néphropathie Diabétique) type 1 diabetes cohort. Logistic and Cox proportional hazards regression models were fitted to estimate odds ratio (OR) (at baseline) and hazard ratio (HR) (during follow-up), with related 95% CI, by increasing biomarker tertiles (T1, T2, T3).Results: Among 478 participants (56% male, mean ± SD age 45 ± 12 years and diabetes duration 29 ± 10 years), 84 patients had LEA at baseline. Baseline history of LEA was associated with shorter LTL (OR for T2 vs. T1 0.62 [95% CI 0.32-1.22] and for T3 vs. T1 0.41 [0.20-0.84]) but not with plasma 8-OHdG (1.16 [0.56-2.39] and 1.24 [0.61-2.55], respectively). New cases of LEA occurred in 34 (12.3%) participants during the 10-year follow-up. LTL were shorter (HR T2 vs. T1 0.25 [95% CI 0.08-0.67] and T3 vs. T1 0.29 [0.10-0.77]) and plasma 8-OHdG higher (2.20 [0.76-7.35] and 3.11 [1.07-10.32]) in participants who developed LEA during follow-up compared with others. No significant interaction was observed between biomarkers on their association with LEA.Conclusions: We report the first independent association between LTL shortening and excess risk of LEA in type 1 diabetes. High plasma 8-OHdG was also associated with incident LEA but partly dependent on cofounding variables. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index
الوصف
تدمد:01495992
DOI:10.2337/dc19-0973