Decreased heart rate variability, decreased vagal tone and changes in sympathetic activity may precede the development of cardiometabolic disease or diabetes.
The cardiac autonomic function is maintained by a dynamic equilibrium between the sympathetic and parasympathetic nervous systems. Cardiac neuropathy can arise from autonomic imbalances, eventually leading to disorders such as myocardial infarction, hypertension, or heart failure. These imbalances are thought to be caused by a hyperactive sympathetic branch and a hypoactive parasympathetic branch, or vice versa. Such dysregulation has been implicated in several disease states, including diabetes. One simple and non-invasive method of measuring autonomic imbalance and vagal activity is using heart rate variability (HRV) as a biomarker. HRV is simply the variation between two consecutive heartbeats. Higher variation is associated with increased parasympathetic activity and decreased sympathetic tone. Previous studies suggest HRV abnormalities, such as a significant reduction in HRV, may precede cardiovascular disease development or diabetes. In Brazil, investigators performed a longitudinal study measuring HRV in adults. The study showed that patients with low HRV had a higher relative risk of developing diabetes, concluding HRV may serve as an independent predictor of diabetes risk.
The Kangbuk Samsung Health Study (KSHS) was a similar study performed in Korea, investigating the predictive power of HRV and the risks of developing diabetes within an Asian population. The cohort study included participants aged eighteen or older who received a comprehensive health-screening yearly, including HRV measurements, between April 2011 and June 2014. In efforts to minimize influence, participants with chronic diseases such as abnormal thyroid function, anemia, COPD, and heart disease were excluded. A total of 54,075 participants were included in the analysis. The primary endpoint was the first diagnosis of diabetes, defined as a fasting plasma glucose level of greater than 125 mg/dl, HbA1c greater than 6.4%, or current use of antihyperglycemic medication. While the gold-standard protocol for estimating HRV is twenty-four-hour measuring, the study employed the more practical and widely used method of short-term HRV recordings. Participants were connected to a medical device, asked to remain calm, and breathe normally, while HRV measurements were recorded for three minutes. HRV was measured as a composite of two variables, time and frequency. Statistical analysis was reported as estimated hazard ratios (HRs) at 95% CI for the development of diabetes using Cox proportional hazard models.
By the end of the study, a total of 1,369 subjects were diagnosed with diabetes. The study revealed increased heart rate, changes in sympathetic regulation, and sympathovagal imbalances all had positive relationships with the incidence of diabetes, with hazard ratios calculated to be 1.41, 1.32, and 1.31, respectively. Specifically, the study showed that patients exhibiting hyperactive sympathetic function were at a 40% increased risk of diabetes. On average, time and frequency HRV variables were lower within patients diagnosed with diabetes. Consistent with previous HRV research including white or black populations, the results from this study suggest that Asian participants with decreased HRV measurements were at increased risk of developing diabetes. Finally, the study grouped data according to sex and found that males had a stronger relationship between abnormal HRV and developing diabetes.
The significant findings of the study suggest that decreased vagal activity caused by overactivation of the sympathetic nervous system may precede diabetes incidence in many Korean adults. The imbalance between the two autonomic branches and diminished heart rate variations were associated with an increased risk of diabetes. Because parasympathetic activation stimulates the secretion of insulin while sympathetic activations inhibit, it makes sense that autonomic imbalances tilting activation towards the sympathetic branch can put patients at risk of diabetes. Patients with increased sympathetic activation will have less insulin secretion and higher glucose levels. The study had several limitations; most notably, no participants over the age of 65 were included, making generalizability difficult. Even still, results from the study add to a growing body of evidence suggesting abnormal HRV may be a predictive factor in patients at risk of developing diabetes. As primary prevention is often the best option for treating diabetes, future HRV monitoring could be used to access patient risk and alert providers of the need for early intervention.
- Decreased heart rate variability is associated with a significant risk of developing diabetes.
- The imbalance between autonomic nervous system branches can lead to increased sympathetic activity reducing insulin secretion.
- Heart rate variability may act as an independent predictor of diabetes.
- Lee, Da Young, et al. “Decreased Vagal Activity and Deviation in Sympathetic Activity Precedes Development of Diabetes.“ Diabetes Care, vol. 43, no. 6, 2020, pp. 1336–43. doi:10.2337/dc19-1384.
- Hoshi, Rosangela., et al. “Decreased Heart Rate Variability as a Predictor for Diabetes—A Prospective Study of the Brazilian Longitudinal Study of Adult Health.“ Diabetes/Metabolism Research and Reviews, vol. 35, no. 7, 2019. doi:10.1002/dmrr.3175.
Stephen Rubano, PharmD. Candidate, USF Taneja College of Pharmacy