Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes.
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.


METHODS
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.
Sampson
Mike J
MJ
Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospital National Health Service Trust, Norwich NR4 7UA, UK. mike.sampson@nnuh.nhs.uk
Winterbone
Mark S
MS
Hughes
Jackie C
JC
Dozio
Nicoletta
N
Hughes
David A
DA
D016022:Case-Control Studies; D002455:Cell Division; D004249:DNA Damage / Q000502:physiology*; D004261:DNA Replication; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000628:therapy; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D018384:Oxidative Stress / Q000235:genetics*; D016615:Telomere
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents