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Leucocyte Telomere Length and Risk of Type 2 Diabetes Mellitus: New Prospective Cohort Study and Literature-Based Meta-Analysis

Author

Listed:
  • Peter Willeit
  • Julia Raschenberger
  • Emma E Heydon
  • Sotirios Tsimikas
  • Margot Haun
  • Agnes Mayr
  • Siegfried Weger
  • Joseph L Witztum
  • Adam S Butterworth
  • Johann Willeit
  • Florian Kronenberg
  • Stefan Kiechl

Abstract

Background: Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies. Methods: Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis. Results: Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I2 = 69%). Conclusions/Interpretation: Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.

Suggested Citation

  • Peter Willeit & Julia Raschenberger & Emma E Heydon & Sotirios Tsimikas & Margot Haun & Agnes Mayr & Siegfried Weger & Joseph L Witztum & Adam S Butterworth & Johann Willeit & Florian Kronenberg & Ste, 2014. "Leucocyte Telomere Length and Risk of Type 2 Diabetes Mellitus: New Prospective Cohort Study and Literature-Based Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-9, November.
  • Handle: RePEc:plo:pone00:0112483
    DOI: 10.1371/journal.pone.0112483
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    References listed on IDEAS

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    1. Jinzhao Zhao & Kun Miao & Haoran Wang & Hu Ding & Dao Wen Wang, 2013. "Association between Telomere Length and Type 2 Diabetes Mellitus: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-7, November.
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    1. Murillo Ortiz Blanca & Martínez Garza Sandra, 2017. "Telomeres are structures at the ends of eukaryotic chromosomes and consist of tandemly repeated DNA sequences. Telomeres shorten with each cell division, and it is well known that telomere length in p," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 2(1), pages 15-17, April.
    2. Ewa Boniewska-Bernacka & Anna Pańczyszyn & Natalia Cybulska, 2019. "Sperm Telomere Length in Men with Normal and Abnormal semen Parameters. A Pilot Study," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 21(1), pages 15639-15645, September.
    3. Francisco Alejandro Montiel Ishino & Claire E. Rowan & Kevin Villalobos & Janani Rajbhandari-Thapa & Faustine Williams, 2022. "A Time-Varying Effect Model (TVEM) of the Complex Association of Tobacco Use and Smoke Exposure on Mean Telomere Length: Differences between Racial and Ethnic Groups Assessed in the National Health an," IJERPH, MDPI, vol. 19(17), pages 1-11, September.
    4. Murillo Ortiz Blanca & Martínez Garza Sandra, 2017. "Telomeres are structures at the ends of eukaryotic chromosomes and consist of tandemly repeated DNA sequences. Telomeres shorten with each cell division, and it is well known that telomere length in p," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 2(1), pages 1-3, April.

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