Abstract
bjectives: Very few data on the role of exercise training on diabetic peripheral neuropathy have been reported. The present study was aimed at investigating the effect of resistance- aerobic training for 16 weeks on Brain-derived Neurotropicfactor (BDNF), Hemoglobin A1c (HbA1c), pain, and Michigan Neuropathy score among type-2 diabetic patients with peripheral neuropathy. Materials and methods: A total of 24 diabetic patients with peripheral neuropathy were randomly assigned to the control (subject:11) and the experimental group (subject:13). The subjects in the experimental group were required to follow a combined of resistance-aerobic training 3 sessions a week for 16 consecutive weeks. Blood samples were taken from all of the participants once before the start of the study, and at the end of the first, second, third, and fourth months. The pain felt by the subjects was measured with the Visual Analogue Scale concurrent with the blood sampling procedure. Findings: The results showed that resistance-aerobic training had no statistically significant effect on the BDNF, Glucose, and HbA1c indexes of the experimental group at P>0.05. However, the level of pain, lower body limb strength, and Michigan Neuropathy score of the experimental group subjects showed a meaningful improvement compared to those of
Visual Analogue Scale concurrent with the blood sampling procedure. Findings: The results showed that resistance-aerobic training had no statistically significant effect on the BDNF, Glucose, and HbA1c indexes of the experimental group at P>0.05. However, the level of pain, lower body limb strength, and Michigan Neuropathy score of the experimental group subjects showed a meaningful improvement compared to those of the subjects in the control group. Conclusion: Although the BDNF serum level did not show any meaningful reduction after resistance-aerobic training, the pain felt, strength, and Michigan neuropathy score improved. It seems highly likely that following resistance-aerobic training can prevent the increase of glucose level in the blood and the reduction of BDNF level in the blood. Keywords: BDNF; Diabetic neuropathies; Exercise; Hemoglobin A1c; Pain Introduction Diabetes has been considered as one of the most alarming complications faced by the health care systems throughout the world in the twentieth century. It is widely believed that the widespread changes in the environment, life style, and behavioral patterns have led to obesity and diabetes which almost always accompany obesity, o s e n referred to by the coined term diabesity encompassing both. Diabetes is associated with some chronic side e v e c t s , the most common of which is diabetic neuropathy. It is estimated that nearly 50% of diabetic patients s u v e r from peripheral neuropathy which is directly associated with poor diabetes control measures, o s e n leading to therapeutic amputations [1]. Patients s u v e r i n g from neuropathic pain usually complain about chronic consistent pain, burning, prickling and tingling caused by gentle touch [2]. Pharmacological control and management of neuropathic pain poses its own clinical challenges in that despite the diverse medications available for the control of neuropathic pain, they are associated with some side e v e c t s [3]. However, non-pharmacological approaches such as electrical stimulation of peripheral nerves, acupuncture, sonography, and regular exercise have been extensively e v e c t i v e in the treatment of neuropathic pain [4]. In addition, these approaches are
diverse medications available for the control of neuropathic pain, they are associated with some side e v e c t s [3]. However, non-pharmacological approaches such as electrical stimulation of peripheral nerves, acupuncture, sonography, and regular exercise have been extensively e v e c t i v e in the treatment of neuropathic pain [4]. In addition, these approaches are b e n e } c i a l because they allow the long-term e v e c t s of type-2 diabetes and the additional costs related to multiple medications prescribed, and the negative side e v e c t s associated with drug combinations to be avoided [5]. Although the e v e c t mechanism of exercise on neuropathic pain is not fully understood, there is growing evidence indicating that regular exercise is e v e c t i v e in improving the dysfunction caused by diabetes and neuropathic pain [6]. e o r e t i c a l l y , the physical activity is likely reduce the development of diabetes in diabetic neuropathy through reducing and glucose level [7] and i n ~ a m m a t i o n [8]. One of the mechanism involved is the mechanism related to the e v e c t of exercise on the level of BDNF. BDNF is one of the members of neurotrophin family considered important for the constant neural functioning, providing support for the survival of neurons in the peripheral and central nervous system.J o u r n a l o f D iabetes & M e t a b o lis m ISSN: 2155-6156 Journal of Diabetes and Metabolism Parsa et al., J Diabetes Metab 2018, 9:11 DOI: 10.4172/2155-6156.1000811 Research Article Open Access J Diabetes Metab, an open access journal ISSN:2155-6156 Volume 9 • Issue 11 • 1000811
Neurotrophins function as support factors on nervous system, preventing damage to neurons in diabetes [9]. Alexis et al. investigated whether the increased level of neurotrophins induced by physical activity could improve the functioning and structure of neurons in diabetes [10]. e results obtained in their study revealed an increased level of BDNF and a reduction of the destructive e v e c t of diabetes on the plasticity of hippocampus neurons. With the same token, the results of the study performed by Kluding et al., showed that a ten-week program of aerobic and resistance training in patients with neurotrophic pain led to a decreased level of pain and the neuropathic symptoms associated with neurotrophic pain [11]. However, S w i s et al., found that a program of nine months of aerobic, resistance and combined training led to no s i g n i } c a n t changes in the BDNF level among diabetic female patients [12]. e American Diabetes Association and e American College of Sports Medicine c o n } r m e d that the rehabilitation program for diabetic patients should involve a combination of aerobic and resistance training so that the therapeutic b e n e } t s of both programs can be obtained. It has been demonstrated that a combination of resistance and aerobic exercise program is e v e c t i v e in controlling blood glucose level and insulin activity, and in reducing the risk factors for cardiovascular diseases [13]. e majority of studies done so far on diabetic individuals either have focused on making comparisons between the potential e v e c t s of aerobic exercises and those of resistance exercises, or have dealt with the potential e v e c t s of one type of exercise such as aerobic exercise [14,15], or have used animals as their subjects [16,17]. In addition, in some of the studies done previously, although the guidelines suggested by ACSM were generally followed, the e y c i e n t volume of the program which could have highest e v
e v e c t s of one type of exercise such as aerobic exercise [14,15], or have used animals as their subjects [16,17]. In addition, in some of the studies done previously, although the guidelines suggested by ACSM were generally followed, the e y c i e n t volume of the program which could have highest e v e c t on the indexes associated with the disease was not dealt with. Given the widespread occurrence of diabetes, the costs and side e v e c t s associated with it, the destructive e v e c t of diabetes on the life quality of the patients, and given that the studies conducted so far have produced contradictory results about the e v e c t of exercise programs on reducing chronic and sever pain level felt, the present study is aimed at investigating the potential e v e c t of a combined exercise program (resistance-aerobic) on BDNF, pain level, and Michigan score among type -2 diabetic patients with peripheral neuropathy. Research Method e population of the study consisted of all diabetic women s u v e r i n g from peripheral neuropathy living in Sabzevar. From among these female patients, a sample of 24 Postmenopausal female patients between 45 to 65 years old were selected. In the selection of the subjects for the study, the following inclusion criteria were employed: being between 45 to 65 years old, having no amputations, s u v e r i n g no sole lesions, having no intense retinopathy, not s u v e r i n g nephropathy, not going under dialysis, not having non-diabetic neuropathy, not having a history of frequent ankle sprains during the last year, and not following a regular exercise program in the last 6 months. All the patients coming to the center were checked for neuropathy by a specialist. In the present study, a score of 2 or higher obtained on the Michigan Neuropathy Questionnaire was considered to be indicative of the presence of neuropathy. Finally all the subjects were interviewed and were
and not following a regular exercise program in the last 6 months. All the patients coming to the center were checked for neuropathy by a specialist. In the present study, a score of 2 or higher obtained on the Michigan Neuropathy Questionnaire was considered to be indicative of the presence of neuropathy. Finally all the subjects were interviewed and were informed of the purpose of the study. From among the patients, samples of 24 patients who were able to go through the resistance exercises with weights, and could do aerobic exercises were selected for the inclusion in the } n a l study. Before the start of the study, all the subjected showed their formal written consent to participate in the study. e subjects were then randomly assigned to the control (subject:11) and experimental group (subject:13). r e e subjects from the experimental group and 4 ones from the control grouped dropped out of the study. Moreover, some exclusion criteria were used in the study such as a subject’s inability to perform the activities or the existence of pain in the chest. e experimental group subjects were gone under electrocardiogram and echocardiogram tests before the study. Finally, before the start of the training program, a blood sample of 3 mm was taken from each subject in experimental and control group at 8 AM a s e r 10 to 12 hours of fasting and was sent to lab for biochemical tests (such as BDNF, glucose and HbA1C measurements). e pain level felt and the blood tests were performed for the subjects a s e r the fourth, eighth, t w e l s h , and sixteenth weeks following the same procedures employed in the pretest stage. Moreover, the cardiovascular system health and the maximum strength of the lower body were evaluated in three stages: pre-study, two months and four months a s e r the completion of the study. In addition, the neuropathy Michigan questionnaire was administered before the study and a s e r 16 weeks following the completion of the study while the subjects were interviewed and
system health and the maximum strength of the lower body were evaluated in three stages: pre-study, two months and four months a s e r the completion of the study. In addition, the neuropathy Michigan questionnaire was administered before the study and a s e r 16 weeks following the completion of the study while the subjects were interviewed and clinically examined so that their neuropathic pain level can be determined before and a s e r the study. In the course of the study, all the subjects continued taking the same glucose inhibiters (such as Glibenclamide and metformin) they took before the study to lower the glucose level in their blood. e sample size estimation e following formula with a power of a=80 was implemented to determine the number of the subjects in the sample. It was determined that the sample should include some 20 subjects. However, to be on the safe side, the } n a l number of the subjects in the sample was decided to be 24. However, from the experimental group some 3 subjects were omitted due to chest pain during the training (a subjects) and the death of close relatives (2 subjects). In the control group, 4 subjects were omitted due to accident (1 subjects) and personal reasons (3 subjects). Criteria for neuropathy L d e n W L } c D W L o n e Michigan Neuropathy Questionnaire was employed to identify peripheral neuropathy among the subjects [18]. Pain estimation e Visual Analogue Scale, which is the most widely used pain measurement instrument in the world, was implemented to measure the amount of desk pained felt by the patients. Maximum strength estimation (1RM) e maximum strength of the lower body limbs (Leg press test) is determined using the following formula [19]. % 1RM=[100 – (2/5×Repetition)] Method of BDNF, glucose and HbA1C measurements Serum BDNF was assayed using a Chemikine BDNF sandwich enzyme-linked immunosorbent assay (ELISA) kit. HbA1c was Citation:Parsa TA, Hosseini SRA, Bije N, Nia MRH (2018) The Study of the Effect of a 16-Week Program of Resistance-Aerobic Training on BDNF, Hba1c,
press test) is determined using the following formula [19]. % 1RM=[100 – (2/5×Repetition)] Method of BDNF, glucose and HbA1C measurements Serum BDNF was assayed using a Chemikine BDNF sandwich enzyme-linked immunosorbent assay (ELISA) kit. HbA1c was Citation:Parsa TA, Hosseini SRA, Bije N, Nia MRH (2018) The Study of the Effect of a 16-Week Program of Resistance-Aerobic Training on BDNF, Hba1c, Pain, and Michigan Neuropathy Score Among Type 2 Diabetic Patients with Peripheral Neuropathy. J Diabetes Metab 9: 811. doi:10.4172/2155-6156.1000811 Page 2 of 8 J Diabetes Metab, an open access journal ISSN:2155-6156 Volume 9 • Issue 11 • 1000811
measured by turbidimetric inhibition immunoassay (Roche, Basel, Switzerland) and to measure blood glucose, the b-glucose test (vakpar, nosaka, and Japan) was used. e ELISA kit was used to determine the insulin levels of the commercial kit (ERG, UK). Training protocol Every training session started with } s e e n minutes of warm-up exercises followed by resistance exercises. e resistance exercises included: Machine chest press, Machine Lat pull -down, Dumbbell Bicep , Dumbbell triceps, Machine Leg Extention, and Machine Prone Leg Curl. Moreover, the subjects performed Sit- up and Push-up. e load were chosen so that the subjects could perform each movement 8 to 12 times } n each station. e workout movements were performed in two sets in the } r s t four weeks. From the } s h to the eighth week, however, the movements were performed in three sets. From the ninth week until the end of the study, they were performed in 4 sets. Moreover, there were 6 stations from the } r s t to the seventh week. During the eighth and ninth weeks, the subjects performed the movements in 7 stations in each session. e n , they had to perform the movements in 8 d i v e r e n t stations until the end of the study. e subjects were asked to repeat the movements 8 to 12 times, with a minute of rest between each sets, and two minutes of rest between stations. $ s e r performing resistance exercises, the subjects started endurance exercises a s e r a short rest (3-5 minute rest). e endurance exercises consisted of aerobic rhythmic exercises and running in intervals of 3 minutes followed by 30 seconds of rest. e intensity of the exercises started with 50% if heart rate reserve in the } r s t week until it reached 75% of heart rate reserve. Similarly, the number of repetitions grew from 5 during the } r s t week, 10 in the thirteenth and fourteenth weeks, 11 in the } s e e n t h , to 12 repetitions
the exercises started with 50% if heart rate reserve in the } r s t week until it reached 75% of heart rate reserve. Similarly, the number of repetitions grew from 5 during the } r s t week, 10 in the thirteenth and fourteenth weeks, 11 in the } s e e n t h , to 12 repetitions in the sixteenth week. At the end of each training session, the subjects were asked to perform some cool-down exercises for 5 to 10 minutes. e exercises were performed three sessions a week at a gym suitable for the subjects in terms of light, temperature, and moisture. Statistical Tests e obtained data were subjected to descriptive statistical analyses including measures of central tendency and standard deviation. e Shapiro-Wilk test was implemented to check the normality of the distribution of data gathered. Moreover, the Levene’s test was performed on the data to examine the homogeneity of the variance in the experimental and control groups. Moreover, a univariate ANOVA and a repeated measure ANOVA were conducted to check the intergroup d i v e r e n c e s and within group d i v e r e n c e s , respectively. In addition, given the lack of homogeneity of variances of the oral interview of the Michigan Screening Questionnaire, an independent t- test was used to check the between group d i v e r e n c e s of the experimental and the control group. All the statistical analyses were performed using SPSS statistical package (version 16), using a s i g n i } c a n c e level of p<0.05. Results e complete results are in Tables 1-5. Parameter Age Weight Height BMIMean (SD) Mean (SD) Mean (SD) Mean (SD) Pre test Experimental 4.06 ± 56.4 11.41 ± 73.25 0.03 ± 1.55 4.06 ± 30.28Control 3.88 ± 58.75 11.23 ± 68.56 0.01 ± 1.59 4.45 ± 26.95 Post test Experimental 4.06 ± 56.4 11.72 ± 72.23 0.03 ± 1.55 4.02 ± 29.83Control 3.88 ± 58.75 10.58 ± 71.11 0.01 ± 1.59 4.27 ±
(SD) Mean (SD) Mean (SD) Mean (SD) Pre test Experimental 4.06 ± 56.4 11.41 ± 73.25 0.03 ± 1.55 4.06 ± 30.28Control 3.88 ± 58.75 11.23 ± 68.56 0.01 ± 1.59 4.45 ± 26.95 Post test Experimental 4.06 ± 56.4 11.72 ± 72.23 0.03 ± 1.55 4.02 ± 29.83Control 3.88 ± 58.75 10.58 ± 71.11 0.01 ± 1.59 4.27 ± 27.96 Table 1: Demographic data at pre-test and post-test in two groups respectively. Leg Press Mean (SD) Significant difference between groups F Pretest Experimental 69.35 ± 48.04 0.28 1.2 Control 50.53 ± 18.84 Second Month Experimental 93.2 ± 64.94 0.03 5.3 Control 42.33 ± 12.72 Fourth Month Experimental 131.95 ± 112.16 0.03 5 Control 47.05 ± 16.95 Significant Difference Within Group P value 0.02F 6.28 Table 2: Depicting the change in mean and standard deviation for parameter of leg press at pre-test, second, and fourth month in two groups respectively. Citation:Parsa TA, Hosseini SRA, Bije N, Nia MRH (2018) The Study of the Effect of a 16-Week Program of Resistance-Aerobic Training on BDNF, Hba1c, Pain, and Michigan Neuropathy Score Among Type 2 Diabetic Patients with Peripheral Neuropathy. J Diabetes Metab 9: 811. doi:10.4172/2155-6156.1000811 Page 3 of 8 J Diabetes Metab, an open access journal ISSN:2155-6156 Volume 9 • Issue 11 • 1000811
Parameter BDNF Pain Glucose HbA1C Mean (SD) Significant difference between groups Mean (SD) Significant difference between groups Mean (SD) Significant difference between groups Mean (SD) Significant difference between groups Pretest Experimental 3.13 ± 0.42 0.45 5.72 ± 5 0.77 134 ± 22.96 0.94 9.27 ± 1.42 0.09 Control 3.53 ± 0.58 5 ± 3.4 179.37 ± 71.9 8.7 ± 1.49 First Month Experimental 3.36 ± 0.18 0.45 4.18 ± 4 0.23 137.66 ± 32.87 0.05 9.55 ± 1.78 0.28 Control 3.66 ± 0.66 7 ± 3.56 200.75 ± 63.63 9.1 ± 1.73 Second Month Experimental 3.29 ± 0.19 0.4 2.8 ± 3 0.04 138.66 ± 31.4 0.39 9.32 ± 1.6 0.34 Control 3.47 ± 0.56 7 ± 4.05 207 ± 77 8.9 ± 2.03 Third Month Experimental 3.4 ± 0.28 0.38 2.5 ± 3 0.02 129.11 ± 25.43 0.86 9.23 ± 1.71 0.6 Control 3.59 ± 0.61 7.5 ± 3.88 154.5 ± 59.01 9.02 ± 1.9 Fourth Month Experimental 3.41 ± 0.33 0.79 2.25 ± 3 0.01 139 ± 20.54 0.49 8.49 ± 1.5 0.5 Control 3.48 ± 0.56 6.5 ± 3.88 156 ± 46.83 8.27 ± 1.67 Significant Difference Within Group P value 0.62 0.42 0.18 0.01F 0.66 0.67 1.94 7.38 Table 3: Depictingthe change in mean and standard deviation for parameters of BDNF, pain, glucose, HbA1C atpretest, } r s t , second, third and fourth month in two groups respectively. Michigan Score ( Interview Part)Mean (SD) Significant difference between groups F Pretest Experimental4.81 ± 2.04 0.42 4.5 Control 6 ± 3.87 Post Test Experimental1.81 ± 1.32 0.00 10.45 Control 6.33 ± 3.39 Significant Difference Within Group P value 0.00F 10.56 Table 4: Depicting the change in mean and standard deviation for parameter of michiganscore ( interviewpart) at pretest and post test in two groups respectively. e results obtained revealed that the combined program of resistance-aerobic exercise for 4 months had no statistically s i g n i } c a n t e v e c t on BDNF, glucose, and HbA1c indexes of the experimental group at P>0.05. However, the level of pain, lower body limb