Abstract
Aims
Individuals with type 2 diabetes show shorter leukocyte telomere length (LTL) compared to people without diabetes. Reduced LTL is associated with increased carotid intima-media thickness (IMT) in healthy subjects. The aim of the study is to assess whether LTL also correlates with IMT in patients with diabetes.
Methods
In a cohort of 104 subjects with type 2 diabetes and atherogenic dyslipidemia, we assessed anthropometric, hemodynamic and metabolic parameters. Common carotid IMT was expressed as the maximum IMT. LTL was assessed by a specific real-time PCR reaction.
Results
At univariate analysis, IMT values were positively correlated with age (p < 0.001), previous history of cardiovascular events (p < 0.005), fasting plasma glucose (p < 0.01), HbA1c (p < 0.05) and negatively correlated with LTL (p < 0.05). In a multivariate model, age (p < 0.001) and LTL (p < 0.05) were the only independent predictors of maximum IMT, with an adjusted R 2 of 0.22.
Conclusions
LTL is an independent predictor of subclinical atherosclerosis pointing to a role of LTL as an early marker of vascular burden and cardiovascular disease also in type 2 diabetes.
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References
Allsopp RC, Chang E, Kashefi-Aazam M et al (1995) Telomere shortening is associated with cell division in vitro and in vivo. Exp Cell Res 220:94–200
Fyhrquist F, Saijonmaa O, Strandberg T (2013) The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol 10:274–283
Sidorov I, Kimura M, Yashin A, Aviv A (2009) Leukocyte telomere dynamics and human hematopoietic stem cell kinetics during somatic growth. Exp Hematol 37:514–524
Neuner B, Lenfers A, Kelsch R et al (2015) Telomere length is not related to established cardiovascular risk factors but does correlate with red and white blood cell counts in a German blood donor population. PLoS ONE 10:e0139308
D’Mello MJ, Ross SA, Briel M, Anand SS, Gerstein H, Paré G (2015) Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ Cardiovasc Genet 8:82–90
Sampson MJ, Winterbone MS, Hughes JC, Dozio N, Hughes DA (2006) Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care 29:283–289
Menke A, Casagrande S, Cowie CC (2015) Leukocyte telomere length and diabetes status, duration, and control: the 1999–2002 National Health and Nutrition Examination Survey. BMC Endocr Disord 15:52
Verzola D, Gandolfo MT, Gaetani G et al (2008) Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am J Physiol Renal Physiol 295:F1563–F1573
Tentolouris N, Nzietchueng R, Cattan V et al (2007) White blood cells telomere length is shorter in males with type 2 diabetes and microalbuminuria. Diabetes Care 30:2909–2915
Olivieri F, Lorenzi M, Antonicelli R et al (2009) Leukocyte telomere shortening in elderly Type 2 DM patients with previous myocardial infarction. Atherosclerosis 206:588–593
Willeit P, Raschenberger J, Heydon EE (2014) Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis. PLoS ONE 9:e112483
Tamura Y, Izumiyama-Shimomura N, Kimbara Y et al (2014) β-cell telomere attrition in diabetes: inverse correlation between HbA1c and telomere length. J Clin Endocrinol Metab 99:2771–2777
Shore AC, Colhoun HM, Natali A et al (2015) SUMMIT consortium. Measures of atherosclerotic burden are associated with clinically manifest cardiovascular disease in type 2 diabetes: a European cross-sectional study. J Intern Med 278:291–302
O’Donnell CJ, Demissie S, Kimura M et al (2008) Leukocyte telomere length and carotid artery intimal medial thickness: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 28:1165–1171
Ardigò D, Bernini F, Borghi C et al (2010) Advanced diagnostic support in lipidology project: role for phenotypic and functional evaluation of lipoproteins in dyslipidemias. Clin Lipidol 5:329–337
Akhter J (1997) The American diabetes Association’s clinical practice recommendations and the developing world. Diabetes Care 20:1044e5
Pugliese G, Solini A, Bonora E et al (2011) The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provides a better definition of cardiovascular burden associated with CKD than the Modification of Diet in Renal Disease (MDRD) Study formula in subjects with type 2 diabetes. Atherosclerosis 218:194–199
Dei Cas A, Spigoni V, Franzini L et al (2013) Lower endothelial progenitor cell number, family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults. Nutr Metab Cardiovasc Dis 23:272–278
Carulli L, Dei Cas A, Nascimbeni F (2012) Synchronous cryptogenic liver cirrhosis and idiopathic pulmonary fibrosis: a clue to telomere involvement. Hepatology 56:2001–2003
Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21
Adaikalakoteswari A, Balasubramanyam M, Mohan V (2005) Telomere shortening occurs in Asian Indian Type 2 diabetic patients. Diabet Med 22:1151–1156
Adaikalakoteswari A, Balasubramanyam M, Ravikumar R, Deepa R, Mohan V (2007) Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy. Atherosclerosis 195:83–89
Salpea KD, Talmud PJ, Cooper JA et al (2010) Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis 209:42–50
Dudinskaya EN, Tkacheva ON, Shestakova MV et al (2015) Short telomere length is associated with arterial aging in patients with type 2 diabetes mellitus. Endocr Connect 4:136–143
Sanders JL, Fitzpatrick AL, Boudreau RM et al (2012) Leukocyte telomere length is associated with noninvasively measured age-related disease: the Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci 67(4):409–416
Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness—a systematic review and meta-analysis. Circulation 115:459–467
Mundstock E, Sarria EE, Zatti H et al (2015) Effect of obesity on telomere length: systematic review and meta-analysis. Obesity (Silver Spring) 23:2165–2174
Vasan RS, Demissie S, Kimura M et al (2008) Association of leukocyte telomere length with circulating biomarkers of the renin-angiotensin-aldosterone system: the Framingham Heart Study. Circulation 117:1138–1144
Révész D, Milaneschi Y, Verhoeven JE, Lin J, Penninx BW (2015) Longitudinal Associations Between Metabolic Syndrome Components and Telomere Shortening. J Clin Endocrinol Metab 100:3050–3059
Raschenberger J, Kollerits B, Ritchie J et al (2015) Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes. Sci Rep 5:11887
Gardner M, Bann D, Wiley L et al (2014) Gender and telomere length: systematic review and meta-analysis. Exp Gerontol 51:15–27
Acknowledgments
This paper has been supported by the DiAL-ER/ADSL research grant from the Regional Health trust-University Program, Emilia-Romagna, Italy and by Local Funds for research “FIL” from the University of Parma of ADC.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Spigoni, V., Aldigeri, R., Picconi, A. et al. Telomere length is independently associated with subclinical atherosclerosis in subjects with type 2 diabetes: a cross-sectional study. Acta Diabetol 53, 661–667 (2016). https://doi.org/10.1007/s00592-016-0857-x
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DOI: https://doi.org/10.1007/s00592-016-0857-x