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Cover page of the Journal of Health Sciences


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 1  |  Page : 70-75

Role of structured exercise therapy on cognitive markers and stress parameters in young patients with Type 2 diabetes mellitus


1 Department of Physiology, JN Medical College, Belagavi, Karnataka, India
2 Department of Medicine, JN Medical College, Belagavi, Karnataka, India

Date of Submission03-Dec-2021
Date of Decision28-Dec-2021
Date of Acceptance04-Jan-2022
Date of Web Publication24-Jan-2022

Correspondence Address:
Dr. Harpreet Kour
Department of Physiology, JN Medical College, Belagavi, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_287_21

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  Abstract 

BACKGROUND AND AIMS: Diabetes mellitus (DM) patients face cognitive impairments owing to neuronal dysfunction following constant oxidative stress. The influence of exercise therapy in the management of DM is widely recognized among the elderly. However, its role among young adults in India is not explored. This study aimed to assess the effect of structured exercise on cognitive markers and stress parameters in young DM patients.
MATERIALS AND METHODS: This interventional study with a pre- and post-model was conducted among 48 newly diagnosed type 2 DM patients who were asymptomatic for cognitive dysfunctions. Glucose profile was recorded by commercially available kits. Cognitive function markers and stress parameters, namely, Tau Protein was estimated in plasma samples using enzyme-linked immunoassay Kit, nitric oxide (NO) by colorimetric method, Catalase and malondialdehyde (MDA) assay by the spectrophotometric method. Patients were trained for the structured exercise therapy as per the protocol and evaluated at the end of 6 months. The change in the quantitative parameters before and after the intervention was assessed by paired t-test. P < 0.05 was considered statistically significant.
RESULTS: The mean of Tau protein, catalase NO, and MDA showed significant statistical difference (P < 0.001) when compared from baseline to postintervention. However, the mean of fasting blood glucose (P = 0.8705), postprandial blood glucose (P = 0.8121), and glycated hemoglobin (P = 0.8121) reported insignificant values from baseline to postintervention.
CONCLUSIONS: Integrated approach of structured exercise therapy has improved the cognitive functions and decreased oxidative stress.

Keywords: Cognitive dysfunction, exercise therapy, glucose, oxidative stress, Type 2 diabetes mellitus


How to cite this article:
Kour H, Kothiwale V A, Goudar SS. Role of structured exercise therapy on cognitive markers and stress parameters in young patients with Type 2 diabetes mellitus. Indian J Health Sci Biomed Res 2022;15:70-5

How to cite this URL:
Kour H, Kothiwale V A, Goudar SS. Role of structured exercise therapy on cognitive markers and stress parameters in young patients with Type 2 diabetes mellitus. Indian J Health Sci Biomed Res [serial online] 2022 [cited 2022 May 22];15:70-5. Available from: https://www.ijournalhs.org/text.asp?2022/15/1/70/336306




  Introduction Top


Diabetes mellitus (DM) is a condition characterized by insufficient insulin production leading to high glucose levels in the body.[1] In the year 2017, the International Diabetes Federation estimated that about 451 million people between the age groups of 18–99 years were identified to be suffering with DM. It was also observed that countries such as India (74 million people) and China (121 million people) showed a higher prevalence rate.[2] In the past three decades, it was observed that DM was a major cause of morbidity and mortality in younger and middle-aged population than the elderly.[3] The main characteristics of type 2 DM are high blood sugar levels, metabolic irregularities including high blood pressure (BP), abnormal lipid profile, and excessive oxidative stress. Before the diagnosis of diabetes, each patient undergoes a prediabetic stage of almost 4 to 5 years, during which various bouts of hypo and hyper-glycemia occur, which can lead to changes in the brain and eventually develop oxidative stress and cognitive dysfunctions.[4]

Glycated hemoglobin (HbA1c) exhibited direct correlations with cholesterol, triglycerides, and low-density lipoprotein cholesterol and inverse correlation with high-density lipoprotein cholesterol. The prediabetes usually has the HbA1c levels as 5.7%–6.4%, while those with 6.4% or higher HbA1c levels have diabetes.[5] The presence of tau protein induce peripheral insulin resistance or disruptions in insulin secretion and is a potential mechanistic link for promoting type 2 diabetics.[6] Catalase, an anti-oxidative enzyme, plays an important role against oxidative stress-generated complications such as diabetes and cardiovascular diseases.[7] The regulation of nitric oxide (NO) metabolism is particularly important in type 2 diabetes, because activation of NO synthase is under insulin control through the Akt pathway. Thus, disturbances of NO generation may be a consequence of insulin resistance, also affecting the vascular response.[8] Malondialdehyde (MDA), a biomarker of lipid peroxidation, has been reported to be significantly raised in diabetes.[9]

Sedentary lifestyle, lack of proper diet, obesity, and lack of exercise add to the causative factors in the pathophysiology of cognitive dysfunctions and oxidative stress in diabetes.[10]

Exercise is one of the three major components in managing type 2 DM along with diet and medications. It has been evidenced that reduction in blood sugar levels and body fat composition improves the risk toward cardiovascular and cardiorespiratory problems, physical functioning, cognitive dysfunctions, and well-being in patients with Type 2 DM. Exercise interventions such as aerobics, yoga, and other physical activities have improved the neurocognitive function in individuals.[11],[12]

Management of type 2 DM requires self-care, but this behavior is impaired due to cognitive dysfunction. Further research and investigations are essential to clarify the association between stress and cognitive dysfunction.[13] There is a lack of concurrence for this interlinking between diabetes and cognitive function due to different study methodologies, study patterns, and France sanalysis.[14],[15],[16] Recently, a battery of papers have documented the positive impact of exercise in the improvement of cognitive functions while decreasing oxidative stress. Targeting young type 2DM patients with structured exercise therapy may delay the onset and complications of cognition and can provide them a better quality of life. Hence the study aimed to assess the effect of structured exercise on cognitive function marker and stress parameters in type 2 DM patients of the age group of 20–45 years.


  Materials and Methods Top


This interventional study with a pre and postdesign was conducted in the Research Laboratory, Department of Physiology. A total of 48 newly diagnosed patients with type 2 DM in the age group of 20–45 years attending the Outpatient Department from the period of April 2017 to October 2018 at a Charitable Hospital and Medical Research Centre, were included in the study. The study was initiated after obtaining approval from the Institutional Ethical Committee (Ref. No. KLEU/Ethic2018-19/D-4570). Patients were briefed about the study, and informed consent was obtained from patients before the start of the study.

Patients with type II DM with a duration of <1 year treated with only diet and oral anti-diabetics were included in the study. Subjects with a history of diabetes of more than 1 year or type 1 DM or having known vascular complication of diabetes, such as coronary artery disease, stroke, nephropathy, retinopathy, and polyneuropathy which, in the investigator's judgment, may have compromised the physical integrity of the patient or other chronic diseases restricting physical activity or with prior regimen of physical exercise and alcoholics or smokers were exempted from the study.

The baseline parameters like age and gender were recorded. Blood samples (10 ml venous samples) were collected and sent to Basic Science Research Laboratory. The patients were then guided regarding “Structured exercise therapy” and were evaluated again at the end of 6 months.

Sample size was calculated using the below-mentioned formula:



Where Z1-α = at 95%, confidence interval = 1.96; Z1-β = at 95%, power of the test = 1.68, Mean and standard deviation (SD) from review of literature for study and control groups were taken: 22.51 ± 2.16 and 20.04 ± 3.02; X1-X2 = Expected impact size

n = (1.68 + 1.96) 2 (2.162 + 3.02 2)/(22.51-20.04) 2 = 43

Accounting drop out cases as 10%, the sample size was calculated as 43/0.9 = 47.7, rounded to 48.

The structured exercise protocol which lasted for 6 months consisted of regular exercises like aerobic and resistance exercises. The first 2 weeks of the regimen consisted of supervised exercise training in Research Laboratory, Department of Physiology. Later, the participants were advised to continue the exercise at their homes regularly. Aerobic exercises were carried out for 30 min for 5 days/week. The regime was structured such that a gap of no more than 2 consecutive days without physical activity was advised. Resistance exercise was performed thrice a week targeting all major muscle groups, 8–10 repetitions into three sets with two kg dumbbells. The resistance exercises included dumbbell flies, seated single leg extension, dumbbell shoulder press, dumbbell bent over row, standing leg curls, dumbbell biceps curls, dumbbell up-right row, dumbbell triceps kickbacks, and abdominal curls. All the patients were provided with detailed instruction booklets describing each resistance training exercise and one pair of 2 kg dumbbells to perform resistance training.[17],[18] Two phone calls per month were made to each study participant and feedback was given to overcome compliance.

Cognitive function marker, i.e., Tau Protein, and stress parameters viz; NO, catalyse, and MDA, glucose profile and body mass index (BMI) were considered as primary outcome variables.

A 10 ml of venous blood sample was collected in EDTA coated vacutainer and plasma was isolated by centrifugation method (REMI Elektrotechnik Limited; REMI R –4°C; 2500 rpm for 15 min). The plasma samples were stored in aliquots as per study requirement in - 80°C (New Brunswick Scientific, England; U410-86).

Tau protein estimation in plasma samples was performed using enzyme-linked immunoassay (ELISA) Kit (RayBIO Human Tau ELISA Kit; GA, United States). The estimation was carried out as per the manual provided with the kit. As instructed in the manual, the plate was washed using microplate washer (BioTek Instruments, USA; 50 TS) and was read using ELISA Plate Reader (BioTek Instruments, USA; EPOCH/2). All chemicals used to assess Tau protein were provided in the kit.[19] NO production was assessed by a colorimetric method, and the absorbance was read at 540 nm.[20] For catalase test, hydrogen peroxide was measured at 405 nm on the spectrophotometer against the blank containing all the components except the enzyme and expressed in kU/l, where k is the first-order rate constant.[21] Thiobarbituric acid levels were estimated as per the spectrophotometric method described by Ohkawa et al.[22] The separated butanol layer was collected and read in a spectrophotometer against a reagent blank at 535 nm. Thiobarbituric reactive substance concentration was expressed in terms of nmol of MDA per mL of plasma.[23],[24] All the tests were performed at Dr. Prabhakar Kore Basic Science Research Laboratory, Belagavi. Glucose profile included fasting blood glucose (FBS), postprandial blood glucose (PPBS), and HbA1C was estimated by using commercially available reagent kits. The American Diabetes Association (ADA) proposed HbA1C ≥6.5% for the diagnosis of diabetes and 5.7%–6.4% for the highest risk to progress to diabetes. BMI kg/m2 was calculated by Quetelet index.[25]

Data analysis was done using R i386.3.5.1 statistical software. Continuous data was represented in the form of mean ± SD, and the categorical variables were represented in the form of frequencies. The change in the quantitative parameters before and after the intervention was assessed by paired t-test. P < 0.05 was considered statistically significant.


  Results Top


A total of 44 subjects with mean age 36.14 ± 4.35 were included in the final analysis, as 4 subjects dropped out. The majority of the subjects were of age group between 34 and 39 years (59.09%) [Table 1].
Table 1: Distribution of subjects by age group

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The mean TAU protein at baseline was 1137.09 ± 391.65 pg/ml, and postintervention at the end of 6 months, it was estimated to be 1881.35 ± 606.97 pg/ml with the difference being statistically significant (P < 0.001). The mean catalase at 405 nm was observed to be 53.71 ± 6.9 ku/l at baseline, and it was 50.88 ± 7.16ku/l at the end of 6-month postintervention, and the difference was statistically significant (P < 0.001). The mean NO was observed to be 50.15 ± 1.57 μmol/l at the baseline, and it was 44.89 ± 1.79 μmol/l at the end of 6-month postintervention, and the difference was statistically significant (P < 0.001). The mean MDA was observed at baseline as 4.77 ± 0.55 nmol/ml and it was 2.99 ± 0.47 nmol/ml at the end of 6-month postintervention, the difference was statistically significant (P < 0.001) [Table 2].
Table 2: Comparison of mean of tau protein and stress parameters

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The mean FBS at baseline was 106.20 ± 11.58 mg/dl, whereas it was 105.82 ± 11.82 mg/dl at, the end of 6 months postintervention with the difference being statistically insignificant (P = 0.871). The mean PPBS at baseline was 140.82 ± 9.95 mg/dl, while postintervention it was 140.3 ± 11.06 mg/dl, and the difference was statistically not significant (P = 0.812). The mean % of Hba1C at baseline was 5.91 ± 0.45, whereas it was 5.86 ± 0.34 at the end of 6 months post intervention, and the difference was statistically insignificant (P = 0.481). The mean weight at baseline was 82.68 ± 7.30 kg, and it was 73.73 ± 7.75 kg at the end of 6 months post intervention, the difference was statistically significant (P < 0.001). The mean BMI at baseline was 31.53 ± 2.40 kg/m2, and it was 28.10 ± 2.45 kg/m2 at the end of 6 months post intervention, the difference was statistically significant (P < 0.001) [Table 3].
Table 3: Comparison of mean of biochemical and anthropometric parameters

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  Discussion Top


The people affected with Type 2 diabetes have reached epidemic proportions all over the world. Diabetes is associated with a variety of metabolic abnormalities, especially hyperglycemia. This might exasperate stress and cognitive functions.[26] Thus, the study aimed to identify the effects of structured exercise on cognitive function and stress parameters in type 2 DM patients younger than 45 years. The severity of Tau pathologies can be associated with the cognitive deficits in diabetes. According to a study conducted by Cohen et al. (2016) and Qu et al. (2014), abnormal tau hyperphosphorylation induces neurodegeneration resulting in cognitive deficits. Inhibition of tau hyperphosphorylation can reverse the formation of abnormal cognition in DM patients.[26],[27] Type 2 DM adversely affects vital organs including the brain, which leads to cognitive decline. This interdependence is caused due to many mechanisms inclusive of blood glucose and direct effect of chronic hyperglycemia on the brain, lipid profile, BP etc.[28] Tau acts as a regulator for insulin signaling, beta-cell functioning, and insulin resistance. Impairment of Tau has shown to promote insulin resistance and insulin deficiency in the brain which can lead to early signs of Alzeimers.[29]

DM is an endocrine disorder associated with cognitive dysfunction, and literature reveals that diabetes causes detrimental effects on a range of cognitive functions as reported by battery of papers.[28] In the current study, Tau protein level was decreased postintervention and was statistically significant (P < 0.001) between baseline and postintervention. Miklossy et al. in their study highlighted that hyperphosphorylated tau was associated with type 2 diabetes, which is a common pathogenetic feature in neurodegenerative disorders including Alzheimer's disease and Type 2 diabetes.[30] A recent observation reported by Zilliox et al. is that p-tau is specifically present in the hippocampal mitochondria of low-capacity running rats, with obesity, hyperinsulinemia, memory, and mitochondrial impairment.[31] Oxidative stress parameters Catalase (ku/l), NO umol/l, and MDA (nmol/ml) were decreased postintervention and were statistically significant (P < 0.001) between baseline and 6-months postintervention. The present study supports the fact that hyperglycemia in diabetic patients increases the production of free radicals and presence of oxidative stressors with an alteration in antioxidant enzyme activities and increased lipid peroxidation (MDA levels) in Type 2 diabetic patients. Similar results were obtained by Goon et al. reported that oxidative stress parameters such as MDA and catalase had significantly dropped at postintervention (P < 0.01). In their study, it was suggested that long-term exercise was an effective means of inducing hormesis that results in enhanced antioxidant protective mechanisms, increased repair mechanisms, and decreased oxidative damages.[32]

This is the first kind of study correlating the cognitive skills with Tau protein and oxidative stress parameters among diabetic population below 45 years. Animal studies showed that aerobic exercise decreased Tau phosphorylation and increased some proteins related to insulin/insulin-like growth factor-1 pathway in hippocampus of diabetic rats. These molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.[33] Grielberger et al., in their study, observed a significant correlation between MDA with neurodegenerative diseases than the control group (P < 0.0001). These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.[34] In another study done by Baldeiras et al., among mild cognitive impairment patients, cognitive function positively correlated (r = 0.298; P = 0.074) with antioxidant levels.[35]

There was a change in the mean observed in stress parameters postintervention that was statistically significant. The percentage of average change in these parameters pre- and postintervention are as follows Tau protein (78.17%), catalases (5.75%), MDA (60.68%), and NO (11.88%). All these parameters and their mechanism are related for cognitive dysfunction.[36],[37] Hence, a positive outcome between the pre- and postintervention model indicates the efficacy of the intervention in managing the disease condition.

A structured exercise therapy consisting of aerobic exercise and resistance exercise for 30 min, 5 days/week, i.e., 150 min/week, led to a significant decrease in BMI (pre-31.54 and post-28.10 kg/m2) and weight loss (pre: 82.68 and post: 73.73 kg) in the study postintervention. According to the ADA and American College of Sports Medicine, 150 min of moderate (50%–70% of a person's maximum heart rate) to vigorous (>70% of maximum heart rate) physical activity per week is recommended for patients with type 2 DM.[38] Studies suggest that physical activities, yoga, aerobic exercises and resistance exercises were found to be effective in managing the complication of type 2 DM.[39],[40] In a recent study, it has been stated that Yoga exercise helped to improve the quality of life, mood and stress levels, coagulation, and cognition of the patients.[41] The uniqueness of this study was various stress parameters assessed such as Tau protein, NO, catalyses, and MDA, and glucose profile and BMI were measured. Second, a follow-up of 6 months was taken which most study lack.

Limitations

There was no significant change observed in the glucose profile in this study which could be due to a shorter study period, and lack of controls as reference were major drawbacks for this study.

Future recommendations

As there is an increase in the prevalence of type 2 DM in young and middle-aged adults, more comparative studies are warranted to evaluate the effects of other physical exercises and Yoga asanas.

Acknowledgement

We Sincerely thank Dr. Sanjay Mishra, Incharge Dr. Prabhakar Kore, Basic Science Research Laboratory for the helping in all biochemical analysis and investigations.

Disclaimer

This was self-funded project.


  Conclusion Top


The current research demonstrated the positive effect of structured exercise such as aerobic and resistance exercise on the stress parameters in the management of type 2 DM. The beneficial effects led to an improvement in the blood glucose level, BMI, and HbA1C levels. Positive effects have been in reducing the effect of stress parameters affecting the cognitive function of the patients. Integrated approach of structured exercise therapy has improved the cognitive functions and decreased oxidative stress.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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