Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy

被引:116
作者
Adaikalakoteswari, Antonysunil [1 ]
Balasubramanyam, Muthuswamy [1 ]
Ravikumar, Radhakrishnan [1 ]
Deepa, Raj [1 ]
Mohan, Viswanathan [1 ]
机构
[1] Madras Diabet Res Fdn, Dr Mohans Diabet Specialties Ctr, Dept Cell & Mol Biol, Madras 600086, Tamil Nadu, India
关键词
oxidative stress; telomere shortening; macroangiopathy; IGT;
D O I
10.1016/j.atherosclerosis.2006.12.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:83 / 89
页数:7
相关论文
共 40 条
[31]  
Nofer Jerzy-Roch, 2005, Expert Rev Cardiovasc Ther, V3, P1071, DOI 10.1586/14779072.3.6.1071
[32]   Telomere length and heredity:: Indications of paternal inheritance [J].
Nordfjäll, K ;
Larefalk, Å ;
Lindgren, P ;
Holmberg, D ;
Roos, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (45) :16374-16378
[33]   Telomere shortening of peripheral blood mononuclear cells in coronary disease patients with metabolic disorders [J].
Obana, N ;
Takagi, S ;
Kinouchi, Y ;
Tokita, Y ;
Sekikawa, A ;
Takahashi, S ;
Hiwatashi, N ;
Oikawa, S ;
Shimosegawa, T .
INTERNAL MEDICINE, 2003, 42 (02) :150-153
[34]   Telomere shortening in human coronary artery diseases [J].
Ogami, M ;
Ikura, Y ;
Ohsawa, M ;
Matsuo, T ;
Kayo, S ;
Yoshimi, N ;
Hai, E ;
Shirai, N ;
Ehara, S ;
Komatsu, R ;
Naruko, T ;
Ueda, M .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) :546-550
[35]   Telomere shortening in atherosclerosis [J].
Samani, NJ ;
Boultby, R ;
Butler, R ;
Thompson, JR ;
Goodall, AH .
LANCET, 2001, 358 (9280) :472-473
[36]   Increased glutathionylated hemoglobin (HbSSG) in type 2 diabetes subjects with microangiopathy [J].
Sampathkumar, R ;
Balasubramanyam, M ;
Sudarslal, S ;
Rema, M ;
Mohan, V ;
Balaram, P .
CLINICAL BIOCHEMISTRY, 2005, 38 (10) :892-899
[37]   Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes [J].
Sampson, MJ ;
Winterbone, MS ;
Hughes, JC ;
Dozio, N ;
Hughes, DA .
DIABETES CARE, 2006, 29 (02) :283-289
[38]   INSULIN RESISTANCE IN PATIENTS OF ASIAN INDIAN AND EUROPEAN ORIGIN WITH NON-INSULIN-DEPENDENT DIABETES [J].
SHARP, PS ;
MOHAN, V ;
LEVY, JC ;
MATHER, HM ;
KOHNER, EM .
HORMONE AND METABOLIC RESEARCH, 1987, 19 (02) :84-85
[39]  
SLAGBOOM PE, 1994, AM J HUM GENET, V55, P876
[40]   Mapping of a major locus that determines telomere length in humans [J].
Vasa-Nicotera, M ;
Brouilette, S ;
Mangino, M ;
Thompson, JR ;
Braund, P ;
Clemitson, JR ;
Mason, A ;
Bodycote, CL ;
Raleigh, SM ;
Louis, E ;
Samani, NJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (01) :147-151