Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis
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posted on 2022-01-27, 20:36 authored by Feifei Cheng, Andrea O Luk, Mai Shi, Chuiguo Huang, Guozhi Jiang, Aimin Yang, Hongjiang Wu, Cadmon KP Lim, Claudia HT Tam, Baoqi Fan, Eric SH Lau, Alex CW Ng, Kwun Kiu Wong, Luke Carroll, Heung Man Lee, Alice P Kong, Anthony C Keech, Elaine Chow, Mugdha V Joglekar, Stephen KW Tsui, Wing Yee So, Hon Cheong So, Anandwardhan A Hardikar, Alicia J Jenkins, Juliana CN Chan, Ronald CW MaObjective
<div><p>Several studies support associations
between relative leukocyte telomere length (rLTL), a biomarker of biological
aging and type 2 diabetes. This study
investigates the relationship between rLTL and the risk of glycaemic
progression in patients with type 2 diabetes.</p>
<p>Research Design and Methods</p>
<p>In this cohort
study, consecutive Chinese patients with type
2 diabetes (N=5,506) from the Hong Kong
Diabetes Register with stored baseline DNA and available follow-up data were
studied. rLTL was measured using a quantitative
polymerase chain reaction. Glycaemic progression was defined as the new need for
exogenous insulin. </p>
<p>Results</p>
<p>The mean(SD) age of the 5,349 subjects was
57.0(13.3) years and mean(SD) follow-up was 8.8(5.4)
years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed
to insulin requirement compared to the remaining subjects (4.43±1.16 vs. 4.69±1.20).
<a></a><a>Shorter rLTL was associated with a higher risk of glycaemic
progression (HR (95%CI) for each unit decrease (</a><a>approximate to</a>
0.2 kilobases):
1.10 (1.06-1.14)), which remained significant after adjusting for confounders. Baseline
rLTL was independently associated with glycaemic exposure during follow-up (Beta=-0.05(-0.06- -0.04)). Each 1 kilobase decrease
in absolute LTL was on average associated with a 1.69-fold higher risk of
diabetes progression (95%CI: 1.35-2.11). Two-sample MR analysis showed per
1-unit genetically decreased rLTL was associated with a 1.38-fold
higher risk of diabetes progression (95%CI: 1.12-1.70).</p>
<p>Conclusions</p>
<p>Shorter rLTL was significantly associated with an
increased risk of glycaemic progression in individuals with type 2 diabetes,
independent of established risk factors. Telomere length may be a useful
biomarker for glycaemic progression in people with type 2 diabetes.</p></div>
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. R.C.M. also acknowledge support from a Croucher Foundation Senior Medical Research Fellowship. R.C.M., F.C. and A.A.H. acknowledge support from the Chinese University of Hong Kong Global Scholarship Programme for Research Excellence. R.C.M. acknowledge support from the Internationalization Faculty Mobility Schemes (Outbound Research Mobility Scheme) from the Office of Academic Links, Chinese University of Hong Kong. F.C. acknowledge support from the Dragon Culture PhD Scholarships for Medical Studies and Faculty Postdoctoral Fellowship Scheme, Chinese University of Hong Kong. M.V.J. and A.A.H. acknowledge JDRF (USA) and JDRF (Australia) CRN for their fellowships, respectively. F.C., A.A.H., and R.C.M. have received support from the Chinese University of Hong Kong Global Scholarship Programme for Research Excellence. F.C. has received support from the Dragon Culture PhD Scholarship.
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