Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy

Abstract Objective Shortening of telomere length has been reported in several conditions including Type 2 diabetes and atherosclerosis. The aims of this study were (1) to assess whether telomere shortening occurs at the stage of pre-diabetes, i.e., impaired glucose tolerance (IGT) and (2) whether telomere shortening was greater in Type 2 diabetic subjects with atherosclerotic plaques. Methods Subjects with impaired glucose tolerance (IGT) ( n  = 30), non-diabetic control subjects ( n  = 30), Type 2 diabetic patients without ( n  = 30) and with atherosclerotic plaques ( n  = 30) were selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing epidemiological population-based study. Southern-blot analysis was used to determine mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leukocyte DNA. Levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and high sensitive C-reactive protein (hs-CRP) were measured by standard methodologies. Carotid intima-media thickness (IMT) was assessed by high resolution B-mode ultrasonography. Results The mean (±S.E.) TRF lengths were significantly lower in IGT subjects (6.97 ± 0.3 kb; p  = 0.002) and lower still in Type 2 diabetic subjects without plaques (6.21 ± 0.2; p  = 0.0001) and lowest in Type 2 diabetic subjects with atherosclerotic plaques (5.39 ± 0.2; p  = 0.0001) when compared to control subjects (8.7 ± 0.5). In IGT subjects, TRF length was positively correlated to HDL cholesterol and negatively correlated to glycated hemoglobin (HbA 1c ), TBARS, PCO, HOMA-IR and IMT. In multiple linear regression analysis, presence of diabetes, HDL cholesterol and increased TBARS levels appear as significant determinants of telomere shortening. Conclusion Telomere shortening is seen even at the stage of IGT. Among subjects with Type 2 diabetes, those with atherosclerotic plaques had greater shortening of telomere length compared to those without plaques.