Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes.
Diabetes Care
; 29(2): 283-9, 2006 Feb.
Article
en En
| MEDLINE
| ID: mdl-16443874
ABSTRACT
OBJECTIVE:
Telomeres are DNA sequences necessary for DNA replication, which shorten at cell division at a rate related to levels of oxidative stress. Once shortened to a critical length, cells are triggered into replicative senescence. Type 2 diabetes is associated with oxidative DNA damage, and we hypothesized that telomere shortening would characterize type 2 diabetes. RESEARCH DESIGN ANDMETHODS:
We studied 21 male type 2 diabetic subjects (mean age 61.2 years, mean HbA(1c) 7.9%) selected to limit confounding effects on telomere length and 29 matched control subjects. Telomere length was measured in peripheral venous monocyte and T-cells (naïve and memory) by fluorescent in situ hybridization and oxidative DNA damage by flow cytometry of oxidized DNA bases. Peripheral insulin resistance (homeostasis model assessment) and high-sensitivity C-reactive protein (hsCRP) were measured.RESULTS:
Mean monocyte telomere length in the diabetic group was highly significantly lower than in control subjects (4.0 [1.1] vs. 5.5 [1.1]; P < 0.0001), without significant differences in lymphocyte telomere length. There was a trend toward increased oxidative DNA damage in all diabetes cell types examined and a significant inverse relationship between oxidative DNA damage and telomere length (r = -0.55; P = 0.018) in the diabetic group. Telomere length was unrelated to plasma CRP concentration or insulin resistance.CONCLUSIONS:
Monocyte telomere shortening in type 2 diabetes could be due to increased oxidative DNA damage to monocyte precursors during cell division. This data suggests that monocytes adhering to vascular endothelium and entering the vessel wall in type 2 diabetes are from a population with shorter telomeres and at increased risk of replicative senescence within vascular plaque.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Monocitos
/
Telómero
/
Estrés Oxidativo
/
Diabetes Mellitus Tipo 2
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Diabetes Care
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido