Comparison of heart rate variability and classical autonomic function tests between type 2 diabetes mellitus and healthy volunteers

Introduction

Type 2 DM is a metabolic disorder with high blood glucose either due to Insulin deficiency or Insulin resistance. Its incidence would be doubled by 2030.^[1] Autonomic nervous system (ANS) innervates almost all organs of the body. ANS maintains homeostatic mechanism of various systems of the body. Autonomic dysfunction in diabetes is called diabetic autonomic neuropathy (DAN). DAN involves gastrointestinal, cardiovascular, genitourinary, sudomotor and metabolic systems.^[2] Cardiac autonomic neuropathy (CAN) results in abnormal heart rate, orthostatic hypotension and silent MI. Decreased HRV is the initial indicator of CAN.^[3] Sympathetic over activity increases heart rate and reduces cyclical beat to beat variation, whereas parasympathetic over activity decreases heart rate and increases beat to beat variation.^[4]

Classical autonomic function tests and HRV are among the accepted methods for diagnosis of cardiovascular autonomic neuropathy in DM. assessment of HRV, hand grip dynamometer, valsalva technique; heart rate change to deep breath provides adequate details of sympathetic and parasympathetic function.

These clinical methods are used in diagnostic approach. The rhythm of the heart is controlled by ANS and it can be evaluated by beat to beat variation of R-R interval. Both HRV and classical autonomic function tests are non-invasive methods for assessing cardio-vagal function. HRV is the most sensitive indicator for assessing sympathovagal imbalance of an individual at any given time.

Materials and Methods

This study was conducted in department of Physiology, PSG IMS&R. This was an observational type of study. 30 cases and 30 controls were included.

The cases were patients diagnosed with type 2 diabetes mellitus for 5 years duration in the age group between 41 to 60 years. The controls were normal healthy volunteers in the same age group. The cases were selected from diabetology OPD and endocrinology OPD according to the inclusion criteria. The controls were selected from medical OPD who were non diabetic healthy volunteers. Details of present history, treatment history were obtained.

The DATA collection tool is a protocol that has patient data, history, physical examination findings and investigation details. The subjects who fulfilled the inclusion criteria were taken for ECG recording for HRV analysis and autonomic function tests in the Physiology research laboratory, PSG IMS&R.

Heart rate variability analysis was done by recording electrocardiogram. It is a non-invasive procedure. Electrocardiograph was done for 5 minutes in a computerized physiography (NEVIQURE- Digital ECG recorder) in Lead 2. HRV analysis was done using Finland software. The resting autonomic activity was assessed by HRV. Two types of parameters are determined by HRV analysis which includes,

Time Domain parameters

Frequency Domain parameters.

Results

Discussion

Various epidemiological and pathological studies states diabetes is an independent risk factor for cardiac disorders both in men and women^{[5] .} In diabetes 65% of death is due to cardio vascular disorders. Myocardial infarction occurs without any preceding symptoms in diabetes^{[6] .}

Autonomic innervation is a primary control mechanism regulating HRV and cardiac performance. Chronic elevated blood glucose promotes progressive autonomic neural dysfunction which parallels the development of peripheral neuropathy. Neuropathy is first seen in the long fibers, hence in diabetes the early feature of autonomic dysfunction is parasympathetic denervation because vagus is the longest nerve.

In normal persons the heart rate has a high degree of beat to beat variability and HRV changes with respiration, increases during inspiration and decreases during expiration^{[7] .} HRV denotes the individual’s autonomic tone and frequency domain measures are considered as best quantitative method for sympathetic and parasympathetic activity.

A predominance of parasympathetic activity causes bradycardia and increase beat-to-beat variation, whereas increased sympathetic tone induces tachycardia and reduce beat-to-beat variations in HRV. High beat-to-beat variation is desirable and lower beat-to-beat variation is an established predictor of cardiac mortality and morbidity. Abnormal HRV predicts the cardiovascular etiology for mortality, coronary atherosclerotic development and cardiac arrhythmias.

Mean RR interval was less and mean HR was more in cases than controls which shows significant decreased parasympathetic activity in cases. SDNN and RMSSD were significantly lower in cases than controls. These findings show that high frequency variations in heart rate are less and vagal modulation of the autonomic nervous system is decreased.

In this study diabetic subjects were having both autonomic nervous system dysfunctions. It was found out that sympathetic as well as parasympathetic systems were altered in diabetes mellitus. Both autonomic function tests and heart rate variability showed significant changes compared to normal subjects.

The frequency domain measures like VLF power, LF power and LF/HF ratio were high in cases than controls. This shows that sympathetic activity is more in cases. The mean heart rate of the cases (81.16 ± 10.9) is higher than the controls (75.56 ± 8.9) which are due to increase in sympathetic tone associated with decrease in parasympathetic tone. This finding is well correlated with previous studies.^{[9], [8]}

Deep breathing test which is specific for parasympathetic activity was also done in this study. This study found that E/I ratio is less in cases than controls. Hence in diabetics the parasympathetic impairment is significant. This finding is similar t o study done by Sundkvist et al.^[10]

Valsalva ratio test in this study showed decrease in cases than controls. Valsalva ratio is more sensitive test for both sympathetic and parasympathetic activity. This study showed impairment of autonomic system in which parasympathetic impairment was more than sympathetic impairment. Our finding correlated with other studies.^{[11] .}

This study gives a solid evidence of impairment of cardiac autonomic activity with dysfunction of both sympathetic and parasympathetic systems with slightly more impairment of parasympathetic system.

Conclusion

Time domain measures of HRV showed significant parasympathetic impairment in cases compared to controls. The frequency domain measures showed increased sympathetic activity and decreased parasympathetic activity. The diastolic blood pressure rise and heart rate rise after hand grip was very less in cases than controls. This finding showed the decreased sympathetic vasomotor efferent tone.

In deep breathing test E/I ratio and Valsalva ratio were less in cases compared to controls. These finding showed impairment of both sympathetic and parasympathetic systems in cases.

Compared with HRV, Classical Autonomic function tests showed very significant impairment (P < 0.0001) of autonomic functions in diabetics than impairment shown by HRV (P < 0.05). This study concludes classical autonomic function tests are superior in assessing autonomic functions than Heart rate variability (HRV).

Source of Funding

None.

Conflict of Interest

None.