Heart Rate Variability and Cardiac Autonomic Dysfunction: Prevalence, Risk Factors, and Relationship to Arterial Stiffness in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study

Diabetes Care. 2019 Nov;42(11):2143-2150. doi: 10.2337/dc19-0993. Epub 2019 Sep 9.


Objective: To determine whether prior type 2 diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

Research design and methods: Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study.

Results: A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN 58.1 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; P < 0.0001) with parasympathetic loss (RMSSD 53.2 ± 36.7 ms vs. controls 67.9 ± 35.2 ms; P < 0.0001) with sympathetic overdrive (LF:HF ratio 1.4 ± 1.7 vs. controls 1.0 ± 1.1; P < 0.0001). Cardiac autonomic dysfunction was present in 8% of TODAY participants, and these participants had greater pulse wave velocity compared with those without dysfunction (P = 0.0001). HRV did not differ by randomized treatment, but higher hemoglobin A1c (HbA1c) over time was independently associated with lower SDNN and RMSSD and higher LF:HF ratio after adjustment for age, race-ethnicity, sex, and BMI.

Conclusions: Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.

Trial registration: ClinicalTrials.gov NCT00081328.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arrhythmias, Cardiac / epidemiology*
  • Arrhythmias, Cardiac / etiology
  • Autonomic Nervous System / physiopathology
  • Autonomic Nervous System Diseases / epidemiology*
  • Autonomic Nervous System Diseases / etiology
  • Child
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / metabolism
  • Heart / physiopathology
  • Heart Rate / physiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Prevalence
  • Pulse Wave Analysis
  • Risk Factors
  • Vascular Stiffness / physiology*
  • Young Adult


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT00081328