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. 2022 Mar 1;45(3):701-709.
doi: 10.2337/dc21-1609.

Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis

Feifei Cheng  1 , Andrea O Luk  1   2   3 , Mai Shi  1 , Chuiguo Huang  1 , Guozhi Jiang  1   2   4 , Aimin Yang  1   2 , Hongjiang Wu  1 , Cadmon K P Lim  1   3 , Claudia H T Tam  1   2   3 , Baoqi Fan  1   2 , Eric S H Lau  1 , Alex C W Ng  1 , Kwun Kiu Wong  1 , Luke Carroll  5 , Heung Man Lee  1   3 , Alice P Kong  1   2   3 , Anthony C Keech  5 , Elaine Chow  1   2 , Mugdha V Joglekar  5   6 , Stephen K W Tsui  7 , Wing Yee So  1   2 , Hon Cheong So  7 , Anandwardhan A Hardikar  5   6 , Alicia J Jenkins  5 , Juliana C N Chan  1   2   3   8 , Ronald C W Ma  1   2   3   8
Affiliations

Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis

Feifei Cheng et al. Diabetes Care. .

Abstract

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 glycemic 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 quantitative PCR. Glycemic 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 with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = -0.05 [-0.06 to -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 Mendelian randomization 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 glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.

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Figures

Figure 1
Figure 1
Cumulative probability of patients with progression to insulin requirement according to tertiles of telomere length. Patients were divided by LTL < 4.153, 4.153 ≤ LTL < 5.092, and LTL ≥ 5.092. rLTL was calculated by negative control (water).
Figure 2
Figure 2
OR for glycemic progression per 1-unit decreased in genetically determined rLTL. Glycemic progression was defined as need for insulin treatment. DM, diabetes mellitus.
See this image and copyright information in PMC

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