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Longitudinal changes in vascular stiffness and heart rate variability among young adults with youth-onset type 2 diabetes: results from the follow-up observational treatment options for type 2 diabetes in adolescents and youth (TODAY) study

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Abstract

Aims

(1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race–ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV.

Methods

Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes over time.

Results

At initial vascular assessment, the 304 participants were a mean age of 21 years, 34% male, and had a mean diabetes duration of 8 years. In more than half the cohort pulse wave velocity, augmentation index and HRV increased over 5 years (p<0.01). Brachial distensibility did not change. There were no differences in the 5-year change by race/ethnicity except for a single HRV measure, where non-Hispanic Blacks had greater worsening of parasympathetic function compared to non-Hispanic Whites, p = 0.008. Blood pressure was related to greater worsening in augmentation index and pulse wave velocity. Higher hemoglobin A1c over time was related to worsening pulse wave velocity and HRV.

Conclusions

Arterial stiffness and HRV worsened over 5 years. Blood pressure and glycemic control may be potential targets to influence adverse changes in arterial stiffness and HRV in young adults with youth-onset type 2 diabetes.

Trial Registration: ClinicalTrials.gov NCT00081328

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All data and materials are available upon request.

Abbreviations

PNN50:

percent of adjacent NN intervals with a difference greater than 50msec

RMSSD:

root-mean-square differences of successive NN intervals

SDNN:

SD of the R–R interval (termed NN interval)

TODAY:

Treatment Options for type 2 Diabetes in Adolescents and Youth

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Acknowledgements

A complete list of individuals in the TODAY Study Group is presented in the Additional file: Data S3. The TODAY Study Group thanks the following companies for donations in support of the study’s efforts: Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi Aventis. We also gratefully acknowledge the participation and guidance of the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service; the opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the respective Tribes and the Indian Health Service.

Funding

This work was completed with funding from NIDDK and the NIH Office of the Director through grants U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The NIDDK project office was involved in all aspects of the study, including: design and conduct; collection, management, analysis, and interpretation of the data; review and approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center & University of Cincinnati, Cincinnati, OH, USA

    Amy S. Shah & Elaine M. Urbina

  2. George Washington University Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD, 20852, USA

    Laure El ghormli & Barbara H. Braffett

  3. Nemours Cardiac Center, Alfred I. DuPont Hospital for Children, Wilmington, DE, USA

    Samuel S. Gidding

  4. University of Pittsburgh, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Kara S. Hughan & Silva Arslanian

  5. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Lorraine E. Levitt Katz

  6. Massachusetts General Hospital, Boston, MA, USA

    Dorit Koren

  7. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Jeanie B. Tryggestad

  8. Children’s Nutrition Research Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA

    Fida Bacha

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  1. Amy S. Shah
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Consortia

The TODAY Study Group

Contributions

ASS, LE, SG, EMU designed the present research question. ASS wrote the first draft of the manuscript. LE analyzed the data. ASS, LE, SG, KSH, LELK, DK, JBT, FB, BB, SA, EMU interpreted the results, critically revised the manuscript, and all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Laure El ghormli.

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Conflict of interest

The authors declare that they have no competing interests to report.

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The authors consent to the publication of this article.

Ethical approval

The study was approved by institutional review boards at all 15 centers and all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

All participants and guardians provided written informed assent and/or consent as appropriate for age and local guidelines.

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Managed by Antonio Secchi.

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Sam Gidding is Retired.

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The TODAY Study Group., Shah, A.S., El ghormli, L. et al. Longitudinal changes in vascular stiffness and heart rate variability among young adults with youth-onset type 2 diabetes: results from the follow-up observational treatment options for type 2 diabetes in adolescents and youth (TODAY) study. Acta Diabetol 59, 197–205 (2022). https://doi.org/10.1007/s00592-021-01796-6

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