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

Authors: SHAH, AMY - Cincinnati Children'S Research Hospital; EL GHOMLI, LAURE - George Washington University; VAJRAVELU, MARY ELLEN - Children'S Hospital - Philadelphia, Pennsylvania; BACHA, FIDA - Children'S Nutrition Research Center (CNRC); FARRELL, RYAN - Case Western Reserve University (CWRU); GIDDING, SAMUEL - Familial Hypercholesterolemia Foundation; LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania; TRYGGESTAD, JEANIE - University Of Oklahoma Health Sciences Center; WHITE, NEIL - Washington University; URBINA, ELAINE - Cincinnati Children'S Research Hospital

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/2019
Publication Date: 11/1/2019
Citation: Shah, A.S., El Ghomli, L., Vajravelu, M., Bacha, F., Farrell, R.M., Gidding, S.S., Levitt Katz, L.E., Tryggestad, J.B., White, N.H., Urbina, E.M. 2019. 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. 42(11):2143-2150. https://doi.org/10.2337/dc19-0993.
DOI: https://doi.org/10.2337/dc19-0993

Interpretive Summary: The changes in heart beat from minute to minute (called heart rate variability) is an early sign of abnormalities in the heart function related to stress hormones. We investigated whether there is evidence of this early dysfunction in heart rate in youth with type 2 diabetes. We studied adolescents and young adults from a multicenter US study: the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. They had heart rate determination over 10 minutes with several measures of beat to beat changes calculated. We found that compared to a group of youth who do not have diabetes, those with type 2 diabetes have less variability in their heart rate, and show evidence of increased activity in their stress hormone system. Dysfunction in this heart rate response was present in 8% of the youth with type 2 diabetes. These youth also had stiffer vessels, which is an early sign of atherosclerosis or hardened arteries. We also noted that the abnormality in the heart function is related to diabetes control and the degree of elevation of blood sugars. Overall these findings show that youth with type 2 diabetes have evidence of early dysfunction in the stress hormone system that affects the heart and vessels function. This is related to diabetes control. This reinforces the importance of better treatments for diabetes to prevent heart disease in these youth.

Technical Abstract: 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-onsetT2D 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. A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN 58.1 6 29.6 ms vs. controls 67.1 6 25.4 ms; P < 0.0001) with parasympathetic loss (RMSSD 53.2 6 36.7 ms vs. controls 67.9 6 35.2 ms; P < 0.0001) with sympathetic overdrive (LF:HF ratio 1.4 6 1.7 vs. controls 1.061.1; 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. Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.