The Effectiveness of Acceptance and Commitment Therapy and Combined with Aerobic Training on Anxiety Symptoms, Insulin Resistance and Lipid Profile in Women with Type 2 Diabetes

iabetes is a non-communicable disease with a silent epidemic and can have a profound effect on a person’s individual, social, and psychological functioning (1). Hyperglycemia is caused by impairments in insulin secretion and insulin D 1. PhD Student, Department of Psychology, Tabriz Branch, Islamic Azad University, Tabriz, Iran. 2. Department of Psychology, Tabriz Branch, Islamic Azad University, Tabriz, Iran. 3. Department of Exercise Physiology, South Tehran Branch, Islamic Azad University, Tehran, Iran. 4. Internal Department, Endocrinologist and Member of Endocrine Research Center, Associate Professor, Tabriz Branch, University of Medical Sciences, Tabriz, Iran.


Introduction
iabetes is a non-communicable disease with a silent epidemic and can have a profound effect on a person's individual, social, and psychological functioning (1). Hyperglycemia is caused by impairments in insulin secretion and insulin IRANIAN JOURNAL OF DIABETES AND OBESITY, VOLUME 13, NUMBER 1, SPRING 2021 receptor function or both and is associated with hyperglycemia, impaired metabolism of carbohydrates, lipids, proteins, and psychological symptoms (2). As insulin resistance (IR) is defined as a decrease in the optimal function of muscle cells for glucose uptake in response to insulin secreted by pancreatic beta cells, it is recognized as one of the pathobiological signs of various diseases including type 2 diabetes mellitus (T2DM) (3). Anxiety disorders are one of the psychological consequences in diabetics and play a central role in the development and control of diabetes in patients. Anxiety is a psychological and physiological state that has cognitive, physical, emotional, and behavioral components, and in fact all human beings experience anxiety in their daily lives (4,5). Aerobic exercise (AE) has beneficial effects on the cardiovascular system and plays a significant role in regulating blood glucose, improving insulin function, improving metabolism of proteins and fats, preventing the complications of diabetes, improving muscle flexibility and strength (6). The results of a study conducted by Ericson et al. revealed that regular exercise training improves the wholebody glucose level by insulin in IR individuals. In addition, failure to engage in regular physical activity may also lead to increased IR (7). Therefore, considering the possible effect of exercise training on blood glucose and insulin secretion, it seems that one of the factors affecting T2DM is exercise training. In a study by Aliza et al., eight week of aerobic exercise in non-obese men with T2DM improved IR (8). As IR is defined as a decrease in the optimal function of muscle cells for glucose uptake in response to insulin secreted by pancreatic beta cells, this index is recognized as one of the pathobiological signs of various diseases including T2DM (3). The effect of physical activity on fat metabolism by increasing insulin sensitivity and high density lipoprotein (HDL-c) and reducing Triglyceride and low density lipoprotein (LDL-c) leads to improved fat and glucose metabolism (6,8). One of the thirdwave cognitive-behavioral therapies, i.e. Acceptance and Commitment Therapy (ACT), is a therapeutic approach that uses acceptance, mindfulness, commitment, and behavior change processes to create more psychological flexibility (9)(10)(11). According to investigations performed in other studies, it can be stated that many studies have been conducted exclusively in the field of psychological problems and aerobic exercise with a focus on diabetes and other research topics; however, what distinguishes the present study from other similar studies is conduction of a concomitant study combining a therapeutic approach based on acceptance and commitment with aerobic exercise. Furthermore, given that no interdisciplinary study has been conducted in this field, the present study aimed at evaluating the effectiveness of ACT combined with aerobic exercise on anxiety symptoms, insulin resistance, and lipid profile in women with T2DM.

Materials and Methods
This quasi-experimental research consisted of female patients with T2DM, who were referred to the specialized clinic of the Northwestern Petroleum Industry Health Organization (Tabriz). Criteria for entering the study were women undergoing drug treatment for T2DM (They only used metformin), having an age range of 30-60 years, having at least two years of T2DM duration and, having clinical signs of anxiety (Beck Anxiety Test), and receiving no regular exercise trainings over the past 6 months. The statistical sample included 60 patients that were randomly divided into four groups: psychological interventions based on ACT, aerobic exercise, psychological interventions based on ACT combined with aerobic exercise, and the control group. 12 patients dropped out of the project in the middle of the study for various reasons (No replacement), However, the number of persons in each group was not less than the normal size (n=12). The present study employed Beck Anxiety Test (pre-and post-test) and laboratory blood tests (blood glucose, insulin, and lipid profile) that was performed before and after the study. Before conducting the research, a briefing session was held with the presence of all subjects that were informed on the objectives of the study as well as the procedures of holding the counseling sessions and exercise trainings, performing blood tests, and creating a virtual communication channel. Moreover, the duration, place, and schedule of the research were explained to the subjects. Then, the consent form with respect to participation in the study was completed by the subjects. The program of psychological interventions was carried out in the form of a treatment workshop based on ACT according to the treatment protocol of the following table (12). Exercise training program lasted 10 weeks, 3 sessions per week for 40-60 minutes and included warming-up, aerobic exercise, and cooling-down steps. The mentioned program was performed in one of the equipped sports clubs of the National Iranian Gas Company of East Azerbaijan in a suitable atmosphere under the supervision of a sports coach and a general practitioner. Exercise intensity of the aerobic exercise program was designed based on the maximum heart rate; hence, trainings were performed with an intensity of 50-75% of the maximum heart rate ( Table 2).
Blood samples were collected and then centrifuged. To measure blood factors, blood serum was stored in a freezer at -70 ° C. Blood glucose level was measured by enzymatic calorimetric method and glucose oxidase technology using a special glucose kit (Pars Azmoon, Tehran, Iran) with the sensitivity of 5 mg/dL. Insulin levels were measured using ELISA kit. IR was calculated by evaluating the homeostasis model based on the equation HOMA-IR = [fasting glucose (mmol/L) × fasting insulin (mU/L)/22.5]. Moreover, total cholesterol, HDL, LDL, and triglyceride were measured using a kit of Pars Azmoon, Iran with the sensitivity of 5 mg/dL. LDL was also calculated based on Friedwald formula LDL = TC-(TG/5+HDL).

Statistical analysis
All statistical analyses were performed using SPSS/Win software, Version 23. Kolmogorov-Smirnov test was used to ensure normal data distribution. The analysis of covariance was used to compare the differences between the groups by controlling the effect of the pretest. Moreover, in case of significant differences between the groups, the Bonferroni post hoc test was used at a significance level of 5%.

Ethical considerations
The present study with the ethical code of IR.IAU.TABRIZ.REC.1398 was approved by the Organizational Ethics Committee for Table 1

. Description of the psychological intervention program Sessions
Workshop Content Session 1 -2 Physiological, behavioral, intellectual, and cognitive symptoms caused by stress, Strategies, and Their management Session 3 -4 Awareness of how diabetes occurs, Genetic issues, Medication therapy, and Strategies to treat diabetes Session 5 -6 Introduction to interpersonal problems, Causes of interpersonal problems, How to overcome interpersonal problems Session 7 -8 Schemas and how they are formed, Identification of early incompatible schemas Session 9 -10 Attention to consciousness by practicing the five senses, Meditation Session 11 -12 How schemas affect interpersonal relationships with schematic-origin behaviors in three behavioral areas Session 13 Identification of how the mind works, Practice with metaphors

Results
Descriptive information of the four groups presenting the mean and standard deviation of research variables after psychological interventions and exercise trainings as compared with before the intervention is provided in Table 3 and 4. The P-value corresponding to table 3,4 shows the results of analysis of covariance test with pre-test adjustment in order to compare the post-test mean between groups. Also according to the table above, there is a significant difference between the groups in anxiety, LDL and HDL indices. ACT approach significantly reduced anxiety symptoms and LDL levels in diabetic women (P-value= 0.001). However, ACT did not significantly alter blood glucose, insulin, IR, triglyceride, total cholesterol, and HDL indexes (P-value> 0.05). The results indicated that aerobic exercise also significantly reduced anxiety symptoms (Pvalue =0.001), significantly increased HDL (P-value =0.008), and non-significantly decreased LDL (P-value =0.06). In addition, aerobic exercise did not significantly change blood glucose, insulin, IR, triglyceride, and total cholesterol indexes (P-value> 0.05). Furthermore, the effect of ACT combined with aerobic exercise significantly increased HDL (P-value= 0.035) and significantly reduced anxiety symptoms (P-value= 0.001) and LDL index (P-value= 0.03). Moreover, ACT combined with aerobic exercise did not significantly change blood glucose, insulin, IR, triglyceride, and total cholesterol indexes (P-value >0.05).

Discussion
Findings of the present study with respect to anxiety index revealed that ACT, AE, and ACT combined with AE, as compared to the control group, significantly reduced anxiety symptoms. These results are consistent with the results of some studies such as FARAHI, Keshavarz, and Hor. The findings of FARAHI et al. have shown that the application of ACT  can be used as an effective psychological intervention in the quality of life of patients with T2DM (13,14). Hor pointed to the significance of the results in their study and stated that the effect of treatment was maintained on the psychological health of t2dm patients at follow-ups (15). Khanjani et al. in their research on the relationship between anxiety and blood cholesterol stated that the symptoms of disease phobia, obsessive compulsive disorder, and anxiety in individuals with high cholesterol were more than those with low cholesterol. Therefore, the findings suggested that high cholesterol levels may be associated with symptoms of anxiety and stress (16). The findings of the present study confirmed that the symptoms of anxiety caused an increase in cholesterol levels, so it is consistent with the findings of the mentioned study that the reduction of anxiety symptoms caused a decrease in cholesterol levels although this finding was restricted to clinical and laboratory observations. Nazari and et al. concluded that 12 weeks of training reduced cortisol and improved stress and anxiety in these patients (17). According to conducted studies, it can be stated that one of the most important problems of patients with T2DM is the existence of anxiety and defects in their mental health function due to problems caused by this disease. ACT has assisted these patients become more in contact with the present moment and their present life experiences and to get rid of the thought that T2DM may have a major impact on their future. In addition, this approach has a cognitive-behavioral aspect and can be an effective way to improve the mental health of patients with T2DM. In this respect, the role of activity and aerobic exercise is highlighted according to conducted studies because exercise is able to decrease anxiety and help to treat diabetes. Moreover, the findings of the present study on lipid profile and blood glucose level have revealed that although ACT approach and AE did not have a significant effect on lowering blood glucose, TG, cholesterol, insulin, and IR, they clinically had noticeable and positive changes in the recovery process of patients with T2DM, as compared with the control group. In addition, the ACT and AE had a significant reducing effect on LDL and increasing effect on HDL, respectively. Furthermore, the combined effect had a significant effect on reducing LDL and increasing HDL. Nasiri et al. in their studies concluded that blood glucose and IR decreased significantly after 8 weeks of combined training; however, insulin levels did not change significantly (18). The results of Tofighi and Babaei indicated that a 12-week period of aerobic exercise decreased the serum lipids of the subjects, and participation in these trainings resulted in a significant positive change in the levels of HDL-C, LDL-C, TC, and TG (19). It should be mentioned that exercise plays a key role in preventing and controlling IR, prediabetic conditions, gestational diabetes, T2DM, and diabetes-related health problems. AE improves insulin function and is effective in managing blood glucose, blood lipids, blood pressure, and quality of life. However, it should be noted that exercise must be performed regularly and continuously in order to enjoy the mentioned benefits (20). The limitation of the present study was the lack of full participation of all individuals until the end of the study. Moreover another limitations was the lack of precise control of the subjects' nutrition and their daily activities.

Conclusions
Overall, each of the methods proposed in the study can be positively effective in reducing psychological and physical symptoms; however, it seems that the combined effect of the two methods in terms of statistical and clinical observations can have additional effects on the trend of decreasing diabetes and its side effects.
IRANIAN JOURNAL OF DIABETES AND OBESITY, VOLUME 13, NUMBER 1, SPRING 2021 Northwestern Petroleum Industry Health Organization, East Azerbaijan Province Gas Company, and the dear patients that cooperated in the implementation of the present research.