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Shortened Relative Leukocyte Telomere Length is Associated with Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes- Analysis from the Hong Kong Diabetes Register

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posted on 10.07.2020 by Feifei Cheng, Andrea O Luk, Claudia HT Tam, Baoqi Fan, Hongjiang Wu, Aimin Yang, Eric SH Lau, Alex CW Ng, Cadmon KP Lim, Heung Man Lee, Elaine Chow, Alice P Kong, Anthony C Keech, Mugdha V. Joglekar, Wing Yee So, Alicia Jenkins, Juliana CN Chan, Anandwardhan A. Hardikar, Ronald CW Ma
Objective: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes.

Research design and methods: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code.

Results: Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA1c, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA1c, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001).

Conclusions: rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.


Funding

This study was supported by the Research Grants Council Theme-based Research Scheme (T12-402/13N) and Research Impact Fund (R4012-18), the Chinese University of Hong Kong Vice-Chancellor One-off Discretionary Fund, and the Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Fund. RCM, FC and AAH acknowledge support from the Chinese University of Hong Kong Global Scholarship Programme for Research Excellence. RCM acknowledge support from the Internationalization Faculty Mobility Schemes (Outbound Research Mobility Scheme) from the Office of Academic Links, Chinese University of Hong Kong. MVJ and AAH acknowledge JDRF (USA) and JDRF (Australia) CRN for their fellowships.

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