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
[1]   Differential gene expression of NADPH oxidase (p22phox) and hemoxygenase-1 in patients with Type 2 diabetes and microangiopathy [J].
Adaikalakoteswari, A. ;
Balasubramanyam, M. ;
Rema, M. ;
Mohan, V. .
DIABETIC MEDICINE, 2006, 23 (06) :666-674
[2]   Telomere shortening occurs in Asian Indian Type 2 diabetic patients [J].
Adaikalakoteswari, A ;
Balasubramanyam, M ;
Mohan, V .
DIABETIC MEDICINE, 2005, 22 (09) :1151-1156
[3]   Menopause modifies the association of leukocyte telomere length with insulin resistance and inflammation [J].
Aviv, A ;
Valdes, A ;
Gardner, JP ;
Swaminathan, R ;
Kimura, M ;
Spector, TD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (02) :635-640
[4]  
Balasubramanyam M., 2003, Diabetes & Metabolism, V29, p4S167
[5]  
Balasubramanyam M, 2004, CURR SCI INDIA, V87, P422
[6]   Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects [J].
Benetos, A ;
Gardner, JP ;
Zureik, M ;
Labat, C ;
Lu, XB ;
Adamopoulos, C ;
Temmar, M ;
Bean, KE ;
Thomas, F ;
Aviv, A .
HYPERTENSION, 2004, 43 (02) :182-185
[7]   Telomere length as an indicator of biological aging - The gender effect and relation with pulse pressure and pulse wave velocity [J].
Benetos, A ;
Okuda, K ;
Lajemi, M ;
Kimura, M ;
Thomas, F ;
Skurnick, J ;
Labat, C ;
Bean, K ;
Aviv, A .
HYPERTENSION, 2001, 37 (02) :381-385
[8]   White cell telomere length and risk of premature myocardial infarction [J].
Brouilette, S ;
Singh, RK ;
Thompson, JR ;
Goodall, AH ;
Samani, NJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (05) :842-846
[9]   Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited [J].
Ceriello, A ;
Motz, E .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (05) :816-823
[10]  
Deepa M, 2003, J Assoc Physicians India, V51, P863