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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 27.01.2022, 20:36 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 Ma
Objective

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.

Research Design and Methods

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.

Results

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). Shorter rLTL was associated with a higher risk of glycaemic progression (HR (95%CI) for each unit decrease (approximate to 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).

Conclusions

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.

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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