PMID- 25390655
OWN - NLM
STAT- MEDLINE
DCOM- 20150706
LR  - 20220318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 11
DP  - 2014
TI  - Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective 
      cohort study and literature-based meta-analysis.
PG  - e112483
LID - 10.1371/journal.pone.0112483 [doi]
LID - e112483
AB  - 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.
FAU - Willeit, Peter
AU  - Willeit P
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria; 
      Department of Public Health and Primary Care, University of Cambridge, Cambridge, 
      United Kingdom.
FAU - Raschenberger, Julia
AU  - Raschenberger J
AD  - Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, 
      Austria.
FAU - Heydon, Emma E
AU  - Heydon EE
AD  - Department of Public Health and Primary Care, University of Cambridge, Cambridge, 
      United Kingdom.
FAU - Tsimikas, Sotirios
AU  - Tsimikas S
AD  - Department of Medicine, University of California San Diego, La Jolla, United 
      States of America.
FAU - Haun, Margot
AU  - Haun M
AD  - Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, 
      Austria.
FAU - Mayr, Agnes
AU  - Mayr A
AD  - Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
FAU - Weger, Siegfried
AU  - Weger S
AD  - Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
FAU - Witztum, Joseph L
AU  - Witztum JL
AD  - Department of Medicine, University of California San Diego, La Jolla, United 
      States of America.
FAU - Butterworth, Adam S
AU  - Butterworth AS
AD  - Department of Public Health and Primary Care, University of Cambridge, Cambridge, 
      United Kingdom.
FAU - Willeit, Johann
AU  - Willeit J
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Kronenberg, Florian
AU  - Kronenberg F
AD  - Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, 
      Austria.
FAU - Kiechl, Stefan
AU  - Kiechl S
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
LA  - eng
GR  - MR/L003120/1/MRC_/Medical Research Council/United Kingdom
GR  - RG/08/014/24067/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20141112
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cholesterol, HDL)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Alcohol Drinking/physiopathology
MH  - Body Mass Index
MH  - C-Reactive Protein/metabolism
MH  - Cholesterol, HDL/blood
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism/pathology
MH  - Female
MH  - Humans
MH  - Leukocytes/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Motor Activity
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Risk Factors
MH  - Sex Factors
MH  - Social Class
MH  - Telomere/*chemistry/metabolism
MH  - *Telomere Shortening
MH  - Waist-Hip Ratio
PMC - PMC4229188
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/11/13 06:00
MHDA- 2015/07/07 06:00
PMCR- 2014/11/12
CRDT- 2014/11/13 06:00
PHST- 2014/06/30 00:00 [received]
PHST- 2014/10/06 00:00 [accepted]
PHST- 2014/11/13 06:00 [entrez]
PHST- 2014/11/13 06:00 [pubmed]
PHST- 2015/07/07 06:00 [medline]
PHST- 2014/11/12 00:00 [pmc-release]
AID - PONE-D-14-28810 [pii]
AID - 10.1371/journal.pone.0112483 [doi]
PST - epublish
SO  - PLoS One. 2014 Nov 12;9(11):e112483. doi: 10.1371/journal.pone.0112483. 
      eCollection 2014.