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ORIGINAL ARTICLE
Year : 2019  |  Volume : 12  |  Issue : 1  |  Page : 11-15  

Assessment of vascular reactivity in young diabetics by cold pressor test and heart rate variability


1 Department of Physiology, Government Medical College and SMHS Hospital, Jammu and Kashmir, India
2 Department of Radio-Diagnosis, SKIMS Bemina, Jammu and Kashmir, India

Date of Submission15-Apr-2018
Date of Acceptance03-Aug-2018
Date of Web Publication18-Jan-2019

Correspondence Address:
Musharaf Bashir
Department of Physiology, Government Medical College and SMHS Hospital, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_60_18

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  Abstract 


Background: Diabetes mellitus (DM) is one of the common causes for autonomic dysfunction. Increased duration of the disease further increases the risk of neuropathy. The cold pressor test (CPT) and heart rate variability (HRV) are two noninvasive tests which are used to study the vascular reactivity. Aim: This study aimed to assess the vascular reactivity in young diabetics with the help of CPT and HRV. Materials and Methods: This study included sixty young adolescents aged 16.71 ± 2.85 years. Thirty adolescents who were diagnosed with type 1 DM (T1DM) were recruited from the outpatient department of endocrinology, and their results were compared with age- and sex-matched thirty controls. Vascular reactivity was assessed with the help of CPT and HRV. Results: The change in systolic (23 ± 10.77 mmHg; P < 0.0001) and diastolic blood pressure (24.87 ± 8.63 mmHg; P < 0.0001) at the end of 1 min of CPT was significantly higher in the diabetic group than controls. Fasting blood glucose was significantly higher in the diabetic group (P < 0.0001) as compared to controls. It was also observed that sympathetic activity was significantly higher in the diabetic group (P = 0.003) whereas parasympathetic activity was significantly reduced in the diabetic group (P = 0.03). Conclusion: Adolescents with T1DM have increased vascular reactivity characterized by increased sympathetic and decreased parasympathetic activity. Thus, it may be concluded that young people with T1DM should be screened for increased vascular reactivity which may serve as a predictor of future hypertension in them.

Keywords: Adolescents, cold pressor test, heart rate variability, hyperreactors, type 1 diabetes mellitus


How to cite this article:
Bashir M, Lone RA, Salroo IN, Sayeed SI. Assessment of vascular reactivity in young diabetics by cold pressor test and heart rate variability. Med J DY Patil Vidyapeeth 2019;12:11-5

How to cite this URL:
Bashir M, Lone RA, Salroo IN, Sayeed SI. Assessment of vascular reactivity in young diabetics by cold pressor test and heart rate variability. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 Feb 16];12:11-5. Available from: http://www.mjdrdypv.org/text.asp?2019/12/1/11/250444




  Introduction Top


The cold pressor test (CPT) is a provocative test which causes generalized sympathetic activation that leads to exaggerated arteriolar constriction and subsequently increased blood pressure.[1] Therefore, CPT is used to assess the neural control of the cardiovascular system by immersing one hand in ice-cold water and observing the increased vascular reactivity which is caused due to stimulation of sensory pain and temperature fibers as well as emotional stimulation leading to an increase in blood pressure and heart rate.[2],[3] CPT has been widely used to assess cardiac autonomic neuropathy in diabetes mellitus (DM), especially sympathetic dysfunction.[4] Hines and Brown were the first to study the vascular reactivity with the help of CPT that leads to an enhanced vascular reactivity/pressor response.[4],[5],[6] Nowadays, heart rate variability (HRV) analysis is used to determine the autonomic imbalance which may help stratify people with sympathetic overactivity/increased vascular reactivity at an earlier stage.[7] HRV serves as an efficient tool to determine the sympathetic predominance, especially in diabetics who are asymptomatic.[8] Thus, CPT along with HRV may be used to study the sympathetic overactivity which serves as a marker for increased vascular reactivity in these young diabetics.[9],[10]

In this study, our main objective was to compare vascular reactivity by CPT and HRV in adolescent diabetics and age- and sex-matched controls.


  Materials and Methods Top


Study design and population

This comparative observational study was carried out after obtaining clearance from the Institutional Ethics Committee of Government Medical College and SMHS Hospital, Srinagar, Jammu and Kashmir, India. All the adolescents diagnosed with type 1 DM (T1DM) were recruited from the endocrinology outpatient department. Adolescents who volunteered to be controls were selected from a higher secondary school. For the study, fifty adolescents with diagnosed T1DM were chosen. Participants who failed to perform CPT were excluded from the study. Finally, thirty adolescents with T1DM were recruited from the age range of 16 to 19 years and thirty healthy controls aged 16–19 years. The mean duration of diabetes in patients was 54.83 ± 33.56 months. All the participants were clearly explained the prerequisites of CPT and HRV and were advised to take a light breakfast on the day of examination at least 3 h before the commencement of the examination. They were also advised not to smoke and take tea/coffee till the examinations were done.

Inclusion criteria

  1. Participants aged between 12 and 19 years
  2. Participants diagnosed with T1DM
  3. Duration of diabetes ≥2 years.


Exclusion criteria

  1. Surgical or medical conditions such as thyroid disorders and chronic kidney failure
  2. Consumption of tea/coffee and drugs that have a direct effect on heart rate such as β-agonists on the day of examination
  3. Participants with diagnosed neuropsychiatric disorders.


All the participants were invited to the autonomic function testing laboratory in the Department of Physiology, Government Medical College and SMHS Hospital, Srinagar, Jammu and Kashmir, India. A sound proof environment, temperature of about 24°C was maintained in the laboratory throughout the procedure.

Procedure of cold pressor test and heart rate variability

Anthropometric and biochemical measurements such as height, weight, body mass index (BMI), and fasting blood glucose were obtained from all the participants. Recent HbA1c values of adolescent diabetics were also recorded. We obtained informed written consent from all the participants or their caretakers. The principles of the Declaration of Helsinki were followed throughout the study. Before the commencement of the tests, all the participants were given an adequate rest of 10 min in a recumbent position. Basal blood pressure was recorded in all the participants.

Cold pressor test

Participants were made to immerse one of their hands in cold water which was maintained at around 4°C throughout the procedure for about 1 min.[11] Temperature of water was constantly measured with the help of a thermometer throughout the procedure. Systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) changes were recorded at the end of 1 min in the contralateral arm with the help of a digital sphygmomanometer (OMRON HEM-8712, Taiwan).

Heart rate variability

Participants were connected to the data acquisition unit PowerLab 26T (ADInstruments, Sydney, Australia). Channel settings were applied. Main and low-pass filter of 50 Hz was applied, and limb lead-II electrocardiogram for 5 min was acquired. Artifacts and ectopic beats were removed manually. Time domain of HRV which included mean heart rate, standard deviation of N–N intervals (SDNN), and root mean square of the successive differences and frequency domain which included very low frequency (VLF), LF, high frequency, and total power (TP) were recorded.

Statistical analysis of data

Data were analyzed on GraphPad Prism 6 (GraphPad Software, San Diego, California, USA). All the data were passed through the D'Agostino–Pearson omnibus normality test. Parametric unpaired t-test was used to analyze data that passed the normality test. Data that failed to pass the normality test were analyzed by nonparametric unpaired t-test known as Mann–Whitney U-test. P < 0.05 was considered statistically significant.


  Results Top


Data from sixty participants were analyzed. The case group consisted of 15 males and 15 females aged 16.24 ± 2.62 years whereas the control group included 15 males and 15 females aged 16.45 ± 2.21 years. Basic characteristics (i.e., age, duration of disease, BMI, fasting glucose, and HbA1c) of both diabetics and controls were compared as shown in [Table 1]. There was no significant difference in age and BMI of the two groups; however, fasting blood glucose was significantly higher in the diabetic group as compared to the controls (P < 0.0001) as shown in [Table 1]. We also observed that HbA1c of diabetic group was significantly higher than the controls (P ≤ 0.001) as shown in [Table 1].
Table 1: Characteristics of diabetics versus controls

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Vascular response of all the participants was compared with the help of CPT and HRV. Comparison of SBP, DBP, ΔSBP, and ΔDBP of diabetics and controls is shown in [Table 2]. There was no significant change in basal SBP (P = 0.54) and DBP (P = 0.49) between the two groups. It was also found that ΔSBP (P < 0.0001) and ΔDBP (P < 0.0001) were significantly higher in diabetics than controls at the end of 1 min of CPT as shown in [Table 2].
Table 2: Comparison of systolic and diastolic blood pressure changes in young diabetics and controls at rest and at the end of 1 min of cold pressor test

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In this study, a significant change in HRV indices between the two groups was observed as shown in [Table 3]. Indices of parasympathetic activity such as SDNN were significantly reduced in diabetics (P = 0.03) as compared to the controls. We observed that indices of sympathetic activity such as VLF (P = 0.002) and LF (P = 0.003) were significantly increased in the diabetic group as shown in [Table 3]. TP (P = 0.005) was significantly higher in diabetics as shown in [Table 3].
Table 3: Comparison of heart rate variability indices in young diabetics versus controls

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  Discussion Top


CPT is a provocative test used to check the pressor response or vascular reactivity.[12] In this study, we observed the blood pressure changes, i.e., ΔSBP and ΔDBP at the end of 1 min of CPT in all the participants. By comparing blood pressure changes between the two groups, we observed that Δ SBP (P < 0.0001) and ΔDBP (P < 0.0001) of diabetics were significantly higher than controls. It is well known that there is an increased cardiovascular and sympathetic response to a stressful stimulus such as CPT which manifests as increased vascular reactivity.[13],[14],[15],[16],[17],[18] Literature suggests that increased vascular reactivity to CPT may lead to a subclinical manifestation of hypertension before actual hypertension is detected.[19] In our study, diabetics had significantly increased ΔSBP and ΔDBP as compared to the controls which suggest that these young diabetics showed increased sympathetic activity to CPT. This sympathetic overactivity was manifested in the form of increased vascular reactivity. Similar findings were observed by Mizushima et al.,[1] who performed CPT in 18 participants to determine vascular reactivity. They found that ten participants had increased vascular reactivity and eight participants had normal reactivity. It was found that almost 60% of the participants had increased vascular reactivity and developed hypertension at some stage. They concluded that increased vascular reactivity to CPT served as an indicator of future hypertension. Amany et al.[20] conducted a study to analyze the effect of CPT on forty healthy, normotensive medical students aged 18–25 years. They found that 40% of these participants had increased vascular reactivity and most of them showed an increase in DBP. They concluded that CPT might be used to check increased vascular reactivity. We also had similar findings in our study.

It is known that HRV analysis may also be used efficiently to detect the influence of sympathetic and parasympathetic system.[8] It may help detect autonomic imbalance such as sympathetic predominance even in subclinical stage; thus, it may be used to detect early increase in sympathetic activity which may lead to increased vascular reactivity.[8] In this study, a comparison of the HRV indices of diabetics and controls was made. It was observed that the indices of sympathetic activity such as VLF and LF[8] were significantly higher in diabetics, suggesting a sympathetic overdrive in them which may be a cause of increased vascular reactivity in them. Furthermore, the indices of parasympathetic activity such as SDNN[8] were significantly lower in diabetics, suggesting decreased parasympathetic activity in them. In this study, these findings suggest that diabetics have sympathetic predominance with an absolute decrease in parasympathetic activity. TP which represents total autonomic activity due to sympathetic and parasympathetic activity[8] was significantly higher in diabetics. This increase in TP was mainly contributed by heightened sympathetic activity in them. Similar findings were observed by Peng et al.,[21] who performed HRV analysis while performing CPT in 101 participants. Both time and frequency domains were studied. They observed that participants with increased vascular reactivity to CPT had increased sympathetic manifested by an increase in VLF and LF in them which was accompanied by a parasympathetic withdrawal, i.e., decreased SDNN. They concluded that participants with increased vascular reactivity had heightened sympathetic activity. Findings in our study were similar.

Limitation

The main limitation of this study is that a single measurement by a digital BP instrument is not the final result. Ideally, for a credible result, an average of three measurements is needed which is not possible for CPT.


  Conclusion Top


Young diabetics have sympathetic overdrive which manifests itself in the form of increased vascular reactivity. Thus, vascular reactivity of young diabetic adolescents should be thoroughly screened to take appropriate steps and minimize the risk of hypertension in them.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mizushima T, Tajima F, Nakamura T, Yamamoto M, Lee KH, Ogata H, et al. Muscle sympathetic nerve activity during cold pressor test in patients with cerebrovascular accidents. Stroke 1998;29:607-12.  Back to cited text no. 1
    
2.
Ifuku H. Cardiovascular responses of blood pressure hyperreactors to the cold pressor test and exercise. J Phys Fit Sports Med 2015;4:331-5.  Back to cited text no. 2
    
3.
Zygmunt A, Stanczyk J. Methods of evaluation of autonomic nervous system function. Arch Med Sci 2010;6:11-8.  Back to cited text no. 3
    
4.
Ahad F, Ashfaq-ul-Hassan, Bhat TA, Robbani I. Evaluation of physiological cardiovascular reactivity to cold pressor stress test. Asian J Biomed Pharm Sci 2015;5:11-14.  Back to cited text no. 4
    
5.
Kasagi F, Akahoshi M, Shimaoka K. Relation between cold pressor test and development of hypertension based on 28-year follow-up. Hypertension 1995;25:71-6.  Back to cited text no. 5
    
6.
Sayinalp S, Sözen T, Ozdoğan M. Cold pressor test in diabetic autonomic neuropathy. Diabetes Res Clin Pract 1994;26:21-8.  Back to cited text no. 6
    
7.
Dreifus LS, Agarwal JB, Botvinick EH, Ferdinand KC, Fisch C, Fischer JD, et al. American College of Cardiology and Cardiovascular Technology Assessment Committee. Heart rate variability for risk stratification of life threatening arrhythmias. J Am Coll Cardiol 1993;22:948-50.  Back to cited text no. 7
    
8.
Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 1996;17:354-81.  Back to cited text no. 8
    
9.
Ifuku H. Cardiovascular responses of blood pressure hyperreactors to the cold pressor test and exercise. J Phys Fit Sports 2015;4:331-5.  Back to cited text no. 9
    
10.
Hada S, Amatya S, Shrestha RK. Cold pressor test in borderline hypertensive university students. Kathmandu Univ Med J (KUMJ) 2016;14:337-41.  Back to cited text no. 10
    
11.
Mei H, Gu D, Rice TK, Hixson JE, Chen J, Jaquish CE, et al. Heritability of blood pressure responses to cold pressor test in a Chinese population. Am J Hypertens 2009;22:1096-100.  Back to cited text no. 11
    
12.
Silverthorn DU, Michael J. Cold stress and the cold pressor test. Adv Physiol Educ 2013;37:93-6.  Back to cited text no. 12
    
13.
Matsukawa T, Gotoh E, Uneda S, Miyajima E, Shionoiri H, Tochikubo O, et al. Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men. Acta Physiol Scand 1991;141:157-65.  Back to cited text no. 13
    
14.
Calhoun DA, Mutinga ML. Race, family history of hypertension, and sympathetic response to cold pressor testing. Blood Press 1997;6:209-13.  Back to cited text no. 14
    
15.
Matthews KA, Woodall KL, Allen MT. Cardiovascular reactivity to stress predicts future blood pressure status. Hypertension 1993;22:479-85.  Back to cited text no. 15
    
16.
Matthews KA, Salomon K, Brady SS, Allen MT. Cardiovascular reactivity to stress predicts future blood pressure in adolescence. Psychosom Med 2003;65:410-5.  Back to cited text no. 16
    
17.
Steptoe A, Marmot M. Impaired cardiovascular recovery following stress predicts 3-year increases in blood pressure. J Hypertens 2005;23:529-36.  Back to cited text no. 17
    
18.
Treiber FA, Kamarck T, Schneiderman N, Sheffield D, Kapuku G, Taylor T, et al. Cardiovascular reactivity and development of preclinical and clinical disease states. Psychosom Med 2003;65:46-62.  Back to cited text no. 18
    
19.
Park J, Middlekauff HR, Campese VM. Abnormal sympathetic reactivity to the cold pressor test in overweight humans. Am J Hypertens 2012;25:1236-41.  Back to cited text no. 19
    
20.
Amany TE, El Azab DR, Khaled Safaa AA. Response to cold pressor test in normotensive adult females. Int J Adv Res Biol Sci 2016;3:219-24.  Back to cited text no. 20
    
21.
Peng RC, Yan WR, Zhou XL, Zhang NL, Lin WH, Zhang YT, et al. Time-frequency analysis of heart rate variability during the cold pressor test using a time-varying autoregressive model. Physiol Meas 2015;36:441-52.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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