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Epidemiology/Health Services Research
Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study
  1. Bailey DeBarmore1,
  2. Ryan J Longchamps2,
  3. Yiyi Zhang3,
  4. Rita R Kalyani4,
  5. Eliseo Guallar3,
  6. Dan E Arking2,
  7. Elizabeth Selvin3,
  8. J Hunter Young3,4
  1. 1Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  2. 2Genetic Medicine, Johns Hopkins University McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA
  3. 3Epidemiology, JHSPH Welch Center for Prevention Epidemiology and Clinical Research, Baltimore, Maryland, USA
  4. 4Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Bailey DeBarmore; bdebarmo{at}live.unc.edu

Abstract

Introduction Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.

Research design and methods We assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.

Results Mean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.

Conclusions Lower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

  • epidemiology
  • cohort
  • adult diabetes
  • mitochondrial DNA
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2020-001204

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    Footnotes

    • Presented at Part of the work presented in this manuscript was presented by BD as a conference poster presentation in 2017 at the American Heart Association Epidemiology and Lifestyles Conference in Portland, Oregon.

    • Contributors BD, DEA, RRK, EG and JHY contributed to the concept and design of the study. YZ, and RJL were responsible for acquisition, analysis and interpretation of the mtDNA-CN data. BD conducted statistical analyses. BD and JHY wrote the manuscript. RJL, DEA, RRK, EG, YZ and ES reviewed/edited the manuscript. BD takes full responsibility for this work as a whole.

    • Funding The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I); National Human Genome Research Institute contract U01HG004402 and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research. YZ, RJL, DEA and EG were also supported by R01HL13573 from the National Institutes of Health.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The ARIC study has been approved by the institutional review boards of participating institutions and all participants provided written informed consent.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement De-identified participant data available on request from the ARIC Coordinating Center (arichelp@unc.edu). BioLINCC URL for ARIC limited dataset: https://biolincc.nhlbi.nih.gov/studies/aric/ and protocol can be found via Clinical Trials Number NCT00005131.

    • Author note At the time of study concept and statistical analyses, BD was affiliated with the Johns Hopkins University Bloomberg School of Public Health. Currently and at the time of manuscript composition, reviewing and submission, BD has been associated with the University of North Carolina at Chapel Hill.