|Year : 2020 | Volume
| Issue : 2 | Page : 111-117
Modulation of blood glucose, oxidative stress, and anxiety level by controlled vestibular stimulation in prediabetes
Remya Paul1, JK Mukkadan2
1 Department of Physiology, Little Flower Hospital and Research Centre, Angamaly, Kerala, India
2 Little Flower Hospital and Research Centre, Angamaly, Kerala, India
|Date of Submission||29-Nov-2019|
|Date of Decision||13-Feb-2020|
|Date of Acceptance||26-Feb-2020|
|Date of Web Publication||22-Jul-2020|
J K Mukkadan
Little Flower Hospital and Research Centre, Angamaly, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Prediabetes is the state of intermediate hyperglycemia. The present study was conducted to analyze the effect of controlled vestibular stimulation (CVS) on blood glucose levels, oxidative stress, and anxiety levels in prediabetic patients. Materials and Methods: This randomized controlled study was conducted at Little Flower Hospital and Research Centre, Angamaly, Kerala. This study comprised 117 prediabetic patients divided into experimental and control groups. Anthropometric measurements, blood pressures, blood glucose levels, and oxidative stress parameters were estimated. State-Trait Anxiety Inventory questionnaire was used to measure the anxiety levels. CVS was provided to the patients in the experimental group using a swing with back to front direction for 3 months. The parameters were reassessed after 3 months of intervention. Comparisons of parameters were carried out by paired t-test, Wilcoxon signed-rank test, and multivariate regression analysis. Results: Blood glucose levels, malondialdehyde level, and anxiety levels were significantly decreased in the experimental group compared to the control group. There was a significant increase in the superoxide dismutase activity after the intervention compared with the control group. Conclusion: The present study confirmed the importance of cost-effective lifestyle intervention for prediabetic patients. CVS can be incorporated in the lifestyle to maintain optimum blood glucose levels and tackle oxidative stress and anxiety
Keywords: Anxiety, oxidative stress, prediabetes, vestibular stimulation
|How to cite this article:|
Paul R, Mukkadan J K. Modulation of blood glucose, oxidative stress, and anxiety level by controlled vestibular stimulation in prediabetes. J Nat Sc Biol Med 2020;11:111-7
|How to cite this URL:|
Paul R, Mukkadan J K. Modulation of blood glucose, oxidative stress, and anxiety level by controlled vestibular stimulation in prediabetes. J Nat Sc Biol Med [serial online] 2020 [cited 2020 Oct 27];11:111-7. Available from: http://www.jnsbm.org/text.asp?2020/11/2/111/290488
| Introduction|| |
Prediabetes is a transitional state between normoglycemia and hyperglycemia. Patients with impaired glucose tolerance 140–199 mg/dl and/or impaired fasting glucose (IFG) 100–125 mg/dl and/or glycosylated hemoglobin (HbA1C) 5.7%–6.4% are defined as prediabetes. It is considered as a higher risk for developing diabetes, stroke, and cardiovascular diseases. There were 373.9 million people aged between 20 and 79 years with impaired glucose tolerance in the world. The overall prevalence of prediabetes in 15 states of India was 10.3%. The prevalence of IFG was higher than the prevalence of impaired glucose tolerance. The incidence rate of IFG was 45.01/1000 person-years in Kerala.
Like Type 2 diabetic patients, prediabetic patients also exhibited increased oxidative stress and disturbed antioxidant system. Oxidative stress occurs when there is an alteration in the redox balance of the cell, causing damage to membranes and vital molecules such as DNA, proteins, and lipids. Oxidative stress has a crucial role in the development and progression of Type 2 diabetes mellitus. Poor mental health is also associated with an increased risk of developing diabetes. There is an association between baseline anxiety and diabetes. This association is likely due to the complicated relationship between anxiety and other risk factors for diabetes. The primary goal of treatment in prediabetic patients is to maintain optimum blood glucose levels. The increased oxidative stress and associated anxiety are the hindrances to the effective control of blood glucose levels. It demands an inexpensive lifestyle intervention.
Controlled vestibular stimulation (CVS) is a physiological intervention shown to inhibit the hypothalamic–pituitary–adrenocortical (HPA) axis and sympathetic–adreno–medullary axis. Vestibular stimulation is found to decrease cortisol level and anxiety. Anatomical pathways support the link between the vestibular system and mental conditions. CVS in stressed Wistar albino rats showed a decrease in oxidative stress markers and glucose levels. In the present study, we aimed to evaluate the effect of CVS on blood glucose, oxidative stress, and anxiety level in prediabetic patients.
| Materials and Methods|| |
This was an open-label, randomized controlled study. The present study was registered in the ISRCTN clinical trial registry (ID: ISRCTN11690727). The study was conducted from August 2017 to January 2019.
The study participants were prediabetic patients among the employees of the Little Flower Hospital and Research Center, Angamaly. The prediabetic patients were identified using fasting plasma glucose according to the American Diabetes Association criteria.
The study was conducted at Little Flower Hospital and Research Center, Angamaly.
Prediabetic patients between 30 and 60 years of both genders were included in the study.
Patients with cardiovascular diseases, infection, liver or kidney diseases, stroke, myocardial infarction, major surgery, malabsorption, pregnant or lactating mothers, chronic smokers and alcoholics, mental health problems, or taking vitamin supplements were excluded from the study. Patients who have undergone any scientific vestibular stimulation programs, any previously known disease, injury, or surgical intervention involving the brain or central nervous system, hearing loss or presence of a cochlear implant, diagnosed vestibular dysfunction, any history of the previous ear or eye surgery, active ear infections, or a perforated tympanic membrane were also excluded from the study.
Body mass index (BMI), waist-to-hip ratio (WHR), blood pressure (BP), fasting blood sugar (FBS), HbA1c, malondialdehyde (MDA), superoxide dismutase (SOD) activity, state anxiety, and trait anxiety were measured.
Institutional ethics committee clearance was obtained before the commencement of the study (IEC/LFMRC/2016/1). All the participants provided written informed consent before participation.
The study participants were selected from the prediabetic population by convenient sampling.
The sample size was calculated according to the primary outcome measure, i.e., blood sugar values of the pilot study. Considering 95% confidence interval level, 80% power, and attrition rate of 5%, the power analysis indicated a sample size of 60 in each group. Hence, a total of 120 patients were recruited in the present study. The patients were randomly divided into experimental and control groups by block randomization. Out of 120 participants, 117 patients completed the study. Two participants from the experimental group and one participant from the control group did not complete the study due to road traffic accident, surgery, and migration, respectively. The flow of the study participants is shown in [Figure 1].
Baseline anthropometric measurements, BP, blood glucose levels, oxidative stress, and anxiety levels were estimated from all the participants. Blood collection was carried out between 7 am and 8 am after 12 h of fasting. The measurements of anthropometry, BP, and anxiety levels were done in a comfortable room after having breakfast on the same day between 10 am and 11 am.
Anthropometric indices included weight, height, and hip and waist circumferences. Waist and hip circumferences were measured according to the WHO STEPS protocol. WHR and BMI were also calculated. BP was measured with a mercury sphygmomanometer (Elko Mercurial Sphygmomanometer 300 manufactured by Anita Industries, New Delhi, India) according to the standard methods. The FBS was measured by the glucose oxidase–peroxidase method. HbA1C was estimated by immune turbidimetric assay.
For the estimation of MDA and SOD, the samples were kept at a temperature of 4°C and centrifuged for 10 min at 4000 rpm. The collected serum was stored at −20°C. The analyses were performed within 1 week. The concentration of SOD and MDA was determined by spectrophotometric method. The SOD activity was estimated using the protocol by Marklund and Marklund. The MDA levels were measured using Buege and Aust method.
Malayalam adaptation of Spielberger State-Trait Anxiety Inventory (STAI) by Mohan Das and Vinod Kumar (1994) was used to assess the anxiety level of prediabetic patients. All the participants could read and write Malayalam. The questionnaire consists of two forms for measuring state and trait anxiety separately. Each scale includes 18 statements and rated on a 4-point scale (not at all, somewhat, moderately so, and very much so). Each form has a minimum score of 18 and a maximum score of 72.
A pilot study was conducted for a period of 3 months (October, November, and December 2016) at Little Flower Hospital and Research Centre, Angamaly. Twenty prediabetic patients were selected and randomly divided into control and experimental groups with 10 patients in each group. Written informed consent was obtained individually. Baseline parameters were collected from the participants. The experimental groups were given the CVS 20 min/day, 5 days/week for 3 months. All the parameters were reassessed after 3 months. The collected data were analyzed. The mean frequency obtained was 14 ± 3.36 cycles/min. The mean distances with which the swing moved front and back were 180.43 ± 27.35 and 169.88 ± 26.29, respectively.
The following conclusions were drawn from the pilot study:
- The CVS intervention was found to be feasible and simple
- The percentage of sample attrition was found to be 5%
- The frequency, intensity, and duration of vestibular stimulation were effective.
Description of intervention
CVS was achieved by swinging on a front-and-back swing direction. Two swings with the provisions for adjustable height, backrest, and seat belt were built using galvanized iron. The length and width of the seat were 40.6 cm and 66.04 cm, respectively. The patients were advised to adjust the height according to their comfort. However, all the participants were comfortable with the height of 203.2 cm. We standardized the intensity, frequency, and duration through the pilot study. The mean values of frequency, intensity, and duration were adopted in the current study. The participants have achieved the intervention with 14 ± 3.36 cycles/min for 20 min/day, 5 days/week for 3 months. The maximum movement of the swing from central to front and central to back was 238.76 cm and 223.52 cm, respectively. The range was kept from center to front 180 cm and center to back 170 cm. No participants reported any side effects.
Measurement of duration, frequency, and intensity
- Duration: The duration of intervention was measured using a timer
- Frequency: The swing cycle involving one back and one front swing was considered as one complete cycle. The total number of cycles per minute was counted and recorded manually
- Intensity: The swing maximum points of the movement were identified, i.e., central point to the maximum front and central point to the maximum back. The measurements of the required movement were marked on the ground with paint on both directions. This was for easy identification of the intensity by which the patient had moved front and back.
Descriptive statistics was used to assess the baseline characteristics of the data. The quantitative variables were expressed as mean ± standard deviation. The comparisons of parameters were carried out by paired t-test and Wilcoxon signed-rank test. The overall comparison of parameters was carried out by multivariate regression analysis. P < 0.05 was considered statistically significant. Statistical Package for the Social Sciences version 20 (SPSS, Inc., Chicago, IL, USA) was used to perform all statistical analysis.
| Results|| |
The study involved 117 prediabetic participants aged 30–60 years. Of this, 53 were male and 64 were female. The characterization of the study participants is displayed in [Table 1]. There was no significant difference in age and gender between the experimental and control groups.
The data in [Table 2] show the comparison of BP and blood glucose levels after the intervention. The result shows that there is a significant decrease in systolic BP, diastolic BP, FBS, and HbA1C in the experimental group after the intervention compared with the control group. The comparison of MDA, SOD, state anxiety, and trait anxiety in the experimental group and control group is given in [Figure 2], [Figure 3], [Figure 4], respectively. The MDA, state anxiety, and trait anxiety levels significantly decreased after the intervention compared with the control group. There is a significant increase in the SOD activity in the experimental group after intervention.
|Table 2: Pre- and posttest comparison of parameters in the controlled vestibular stimulation group and control groups|
Click here to view
|Figure 2: Comparison of malondialdehyde level (nmol/ml) in the experimental and control groups|
Click here to view
|Figure 3: Comparison of superoxide dismutase (U/ml) in the experimental and control groups|
Click here to view
|Figure 4: Comparison of state anxiety and trait anxiety in the experimental and control groups|
Click here to view
Data in [Table 3] show gender-wise comparison of parameters in the experimental and control groups. It shows that all the parameters were significantly decreased in the experimental group compared with the control group, except SOD in both genders. There was a significant increase in SOD in both genders after the intervention. [Table 4] explains both gender-wise and group-wise comparisons of parameters among the study population using multivariate regression analysis. It shows that the intervention influences all parameters, except diastolic BP. It also indicated that gender has a significant influence only on FBS and state anxiety.
|Table 3: Gender wise comparison of parameters in the experimental and control groups|
Click here to view
| Discussion|| |
Prediabetes is associated with elevated BP. Studies reported that prediabetes is an independent risk factor of hypertension. The presence of hypertension in the prediabetic stage is a risk factor for having the vascular disease at the time of diagnosis of Type 2 diabetes. In the present study, we observed elevated BP in prediabetic patients. We also found that there were significant reductions in the systolic and diastolic BPs after vestibular stimulation in both genders. Cardiac regulation is mainly carried out by sympathetic nervous system. The vestibular system has a vital role in the activation of the sympathetic nervous system. The vestibulosympathetic reflex assists in BP regulation in humans and animals., This reflex is thought to be the reason for the reduction in BP after vestibular stimulation. Hallgren et al. also indicated that the intact otolith system has a crucial role in BP instability during orthostatic challenges. Our finding is in agreement with the study by Clench and Williams, who reported that vestibular stimulation significantly decreased systolic BP in adults. Tang and Gernandt observed that declination in the systemic BP was elicited in animals when using low-strength vestibular stimulation. The present finding is also consistent with another study, in which the reduction of systolic BPs after linear vestibular stimulation was observed.
The brain has a crucial role in glucose homoeostasis through the control of pancreatic secretion. The hypothalamus can also affect metabolic functions by neuroendocrine connections such as the HPA axis. Markia et al. reported the existence of a vestibulo-paraventricular polysynaptic pathway and explained that the HPA axis is modulated by vestibular stress. Single shock vestibular stimulation evokes a response from the ipsilateral vagus nerve. Vagal nerve stimulation enhances insulin secretion. In the present study, we observed that FBS and HbA1C were significantly decreased in prediabetic patients after the intervention compared with the control group even though the blood glucose levels were not converted to the normoglycemic level. The observations confirmed the results obtained by the case study conducted in Type 2 diabetic patients undergoing vestibular stimulation. The finding is concordant with the study by Smitha et al., in which they showed that CVS is effective in reducing blood glucose level in stressed Wistar albino rats.
The correlation between the vestibular system and anxiety may be due to the projections from the vestibular nuclei to cortical and subcortical brain regions that are also involved in the emotional process. These regions include insula, the cingulate, the hippocampus, and the parabrachial nucleus. The dorsal raphe and locus coeruleus send out serotonergic and noradrenergic projections to vestibular nuclei in the brain stem. Winter et al. showed that natural vestibular stimulation could bring a modification of mood state and anxiety. State anxiety and trait anxiety significantly reduced in the CVS group after intervention in both males and females. Studies among college students reveal that CVS can consider as a stress relief therapy. Another type of vestibular stimulation was also found to be effective in decreasing anxiety level in the student population.
Disturbance of oxidant–antioxidant balance was seen in prediabetes. Studies have shown higher MDA and lesser SOD in prediabetic patients.,, In the present study, we observed significant reduction in the MDA level and increase in the SOD activity in prediabetic patients after 3 months of CVS in both genders. Kao et al. reported that vestibular rehabilitation significantly reduces MDA level and enhanced SOD activity in patients with chronic dizziness. Wang et al. also observed a similar finding that SOD activity increased after rotatory vestibular stimulation in rats. CVS also reduced the MDA level and increased SOD activity in stressed Wistar albino rats. High BP and increased anxiety are associated with increased oxidative stress and disruption of the antioxidant system., In the present study, vestibular stimulation significantly reduces BP, blood glucose levels, and anxiety. This may be one of the reasons for reducing oxidative stress in the present population.
The detailed mechanism behind the present outcome is to be studied.
| Conclusion|| |
The findings strongly confirmed that blood oxidative stress and anxiety in prediabetic patients could be reduced by CVS. It is also useful in maintaining optimum blood glucose levels in prediabetic populations. It can incorporate into the lifestyle of prediabetic patients for effective management of the disease.
The authors are thankful to the Management, Little Flower Hospital and Research Centre, for providing the needed facilities for the research work. We thank Dr. Mohan Das and Dr. Vinod Kumar for permitting to use their Malayalam translation of STAI questionnaire in the present study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018;41:S13-27.
International Diabetes Federation. IDF Atlas. 9th
ed. Brussels, Belgium: International Diabetes Federation; 2019. p. 50.
Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al
. Prevalence of diabetes and prediabetes in 15 states of India: Results from the ICMR-INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol 2017;5:585-96.
Vijayakumar G, Manghat S, Vijayakumar R, Simon L, Scaria LM, Vijayakumar A, et al
. Incidence of type 2 diabetes mellitus and prediabetes in Kerala, India: Results from a 10-year prospective cohort. BMC Public Health 2019;19:140.
Gunawardena HP, Silva R, Sivakanesan R, Ranasinghe P, Katulanda P. Poor glycaemic control is associated with increased lipid peroxidation and glutathione peroxidase activity in type 2 diabetes patients. Oxid Med Cell Longev 2019;2019.
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 2012;5:9-19.
Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links. Int J Physiol Pathophysiol Pharmacol 2019;11:45-63.
Smith KJ, Deschênes SS, Schmitz N. Investigating the longitudinal association between diabetes and anxiety: A systematic review and meta-analysis. Diabet Med 2018;35:677-93.
Sailesh KS, Mukkadan JK. Psychoneuroimmuno modulation by controlled vestibular stimulation. J Clin Exp Res 2013;1:68-70.
Gurvich C, Maller JJ, Lithgow B, Haghgooie S, Kulkarni J. Vestibular insights into cognition and psychiatry. Brain Res 2013;1537:244-59.
Smitha KK. Comparative Effect of Different Stress on Free Radical Generation and the Impact of Controlled Vestibular Stimulation on Stressed Albino Wistar Rats. PhD. Thesis, Mahatma Gandhi University, Kottayam, India; 2016.
World Health Organization. WHO Stepwise Approach to Surveillance (steps). Geneva: World Health Organization; 2008b.
Smith L. New AHA recommendations for blood pressure measurement. Am Fam Phys 2005;72:1391-8.
Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969;6:24.
Teitz NW. Textbook of Clinical Chemistry. Philadelphia: W. B. Saunders Company; 1999. p. 794-5.
Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-74.
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.
Alice PM. The Effectiveness of Stress Management Programme on Cardiac Surgical Patients. PhD. Thesis, Mahatma Gandhi University, Kottayam, India; 2003.
Golden SH, Wang NY, Klag MJ, Meoni LA, Brancati FL. Blood pressure in young adulthood and the risk of type 2 diabetes in middle age. Diabetes Care 2003;26:1110-5.
Lu HJ, Li MH, Li MZ, Park SE, Kim MS, Jin YZ, et al
. Functional connections of the vestibulo-spino-adrenal axis in the control of blood pressure via the vestibulosympathetic reflex in conscious rats. Korean J Physiol Pharmacol 2015;19:427-34.
Ray CA, Carter JR. Vestibular activation of sympathetic nerve activity. Acta Physiol Scand 2003;177:313-9.
Hallgren E, Migeotte PF, Kornilova L, Delière Q, Fransen E, Glukhikh D, et al
. Dysfunctional vestibular system causes a blood pressure drop in astronauts returning from space. Sci Rep 2015;5:17627.
Clench M, Williams B. Psycho/physiological effects of vestibular and audio stimulation: The Trinity Table. Subtle Energies Energy Med 2005;16:29-32.
Tang PC, Gernandt BE. Autonomic responses to vestibular stimulation. Exp Neurol 1969;24:558-78.
Kumar SS, Rajagopalan A, Mukkadan JK. Vestibular Stimulation for Stress Management in Students. J Clin Diagn Res 2016;10:CC27-31.
Guemes A, Georgiou P. Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes. Bioelectron Med 2018;4:9.
Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci 2006;8:383-95.
Markia B, Kovács ZI, Palkovits M. Projections from the vestibular nuclei to the hypothalamic paraventricular nucleus: Morphological evidence for the existence of a vestibular stress pathway in the rat brain. Brain Struct Funct 2008;213:239-45.
Akert K, Gernandt BE. Neurophysiological study of vestibular and limbic influences upon vagal outflow. Electroencephalogr Clin Neurophysiol 1962;14:904-14.
Kaneto A, Miki E, Kosaka K. Effects of vagal stimulation on glucagon and insulin secretion. Endocrinology 1974;95:1005-10.
Kumar SS, Archana R, Mukkadan JK. Controlled vestibular stimulation: Physiological intervention in diabetes care. Asian J Pharmaceut Clin Res 2015;8:315-18.
Smitha KK, Dinesh KS, Mukkadan JK. Standardisation of controlled vestibular stimulation for optimal stress relief in albino wistar rats. Pharma Innovat J 2015;4:1-3.
Jacob RG, Furman JM. Psychiatric consequences of vestibular dysfunction. Curr Opin Neurol 2001;14:41-6.
Winter L, Kruger TH, Laurens J, Engler H, Schedlowski M, Straumann D, et al
. Vestibular stimulation on a motion-simulator impact on mood states. Frontiers Psychol 2012;3:499.
Pasquier F, Denise P, Gauthier A, Bessot N, Quarck G. Impact of galvanic vestibular stimulation on anxiety level in young adults. Front Syst Neurosci 2019;13:14.
Likidlilid A, Patchanans N, Peerapatdit T, Sriratanasathavorn C. Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. J Med Assoc Thai 2010;93:682-93.
Su Y, Liu XM, Sun YM, Jin HB, Fu R, Wang YY, et al
. The relationship between endothelial dysfunction and oxidative stress in diabetes and prediabetes. Int J Clin Pract 2008;62:877-82.
Mahat RK, Singh N, Rathore V, Arora M, Yadav T. Cross-sectional correlates of oxidative stress and inflammation with glucose intolerance in prediabetes. Diabetes Metab Syndr 2019;13:616-21.
Kao CL, Tsai KL, Cheng YY, Kuo CH, Lee SD, Chan RC. Vestibular rehabilitation ameliorates chronic dizziness through the SIRT1 axis. Front Aging Neurosci 2014;6:27.
Wang ZB, Han P, Tu Y, Liu WY, Tao BL, Zhang LC, et al
. Oxidative stress is not involved in motion sickness in mice. CNS Neurosci Ther 2013;19:611-6.
Rodrigo R, González J, Paoletto F. The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res 2011;34:431-40.
Bouayed J, Rammal H, Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxid Med Cell Longev 2009;2:63-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]