The effect of 8 weeks of aerobic training and omega-3 supplement consumption on inflammatory indices of type 2 diabetic patients

Master's Thesis of Physical Education and Sports Sciences

(Exercise Physiology)

Abstract

The purpose of this study was to study the effect of omega-3 supplementation during an increasing aerobic training period on the response of pro-inflammatory cytokines TNF-?, ?1-IL and insulin resistance index in type 2 diabetic men. For this purpose, 30 men with type 2 diabetes with an average age of 51.75±7.8 years were divided into three supplement consumption groups (10 people), aerobic exercise group with supplement consumption (10 people) and control group (10 people) as research subjects. The supplement group and the aerobic exercise group along with supplement consumption did aerobic activity for 8 weeks, 3 sessions per week and 40 to 50 minutes each session, which included running on a treadmill with increasing intensities. Blood samples were collected to measure the amount of cytokines TNF-?, ? 1-IL by ELISA method in three stages, week zero, week four (mid-test) and week eight (post-test) from the fasting subjects. Statistical analysis of the data was done through ANOVA with repeated measurements. Results: It showed that the consumption of 6 grams of supplement containing 3.6 grams of omega-3 for 8 weeks caused a significant decrease in the resting levels of cytokines TNF-? (p<0.001) and ?1-IL in response to increasing aerobic exercises with the consumption of omega-3 supplements (p<0.000), also the results showed that the insulin resistance index was significantly reduced in response to increasing aerobic exercises with the consumption of omega-3 supplements. (p<0.000). Conclusion: While omega-3 supplementation reduces insulin resistance and inflammatory indicators, adding aerobic exercise to this nutritional intervention doubles this improvement. 1-Introduction Diabetes, as the most common disease caused by metabolic disorders (1), is considered an important global challenge (2). The increase in the number of patients with type 2 diabetes indicates a global epidemic. It is predicted that the prevalence of this disease will reach a figure equivalent to 4.4% of the world's population by 2030. The national study on the risk factors of non-communicable diseases estimated the prevalence of diabetes in Iran in 2008 at 7.7% (with a 95% confidence interval: (7.5-7.9)) (3). The World Health Organization has estimated that the number of diabetic patients in Iran will reach more than six million by 2030 (3). Considering the increase in life expectancy in Iran, there is no doubt that the prevalence of diabetes complications is increasing day by day. Diabetes is associated with numerous short-term and long-term complications, which are not reversible in many cases (4). The morbidity and mortality caused by these complications is considered one of the most important health-treatment issues in the world (5), and for this reason, special attention has been paid to the investment to control diabetes (4).

Given that 2.5-3% of the world's people suffer from diabetes, huge costs are imposed annually on the health organizations of different countries of the world to control this disease (6). A lot of research has been done on the relationship between type 2 diabetes and inflammation. It has been observed that inflammatory biomacro are increased in type 2 diabetes. CRP, interleukin-6 and TNF-? can be mentioned among these bio-macros (6,7,8). On the other hand, it has been observed that omega-3 fatty acids can reduce inflammation through certain structures and functions. These mechanisms include:

A: Preventing the inflammatory reaction caused by arachidonic acid (9)

B: Preventing the release of arachidonic acid by lipoprotein lipase (10)

C: Reducing the content of arachidonic acid in cell membranes (11)

D: Suppressing the activity of cyclooxygenase-2 (2-COX) which converts arachidonic acid to converts prostaglandin-2 and thromboxane-2 (12).

As research has shown that omega-3 fatty acids can effectively reduce the production of cytokines (13). Of course, it takes a certain amount of time for the anti-inflammatory effects of omega-3 fatty acids to appear (14). Human studies have also confirmed this (7). Although this effect has not been observed in some patients with Alzheimer's disease (15). Omega-3 and omega-6 fatty acids can inhibit the production of interleukin 1 and 2, TNF-? in human lymphocyte cells in the laboratory environment and in vivo (16). Also, supplementation with omega-3 fatty acids strongly reduces serum CRP levels (17). The effect of omega-3 fatty acids on inflammation in diabetic patients has been studied.However, the results of these researches are contradictory (18).

On the other hand, in recent years, physical activity and exercise have been proposed as a way to control diabetes along with nutrition and medicine (19). Aerobic activity is an accepted therapeutic procedure for people with type 2 diabetes, because it has a beneficial effect on the glycemic profile and reducing the risk factors of cardiovascular diseases, including insulin resistance (20). The reduction of glucose tolerance and insulin resistance in relation to obesity has been investigated and it has been shown that physical activity and exercise have a favorable effect on reducing insulin resistance in people with type 2 diabetes (21). So far, the effect of sports training with omega-3 supplementation on the levels of TNF-? and IL-1 has not been investigated in interaction with each other. Past research states that intensive training programs increase insulin sensitivity and reduce subcutaneous and visceral fat tissue in middle-aged men with type 2 diabetes (19). Due to the fact that inflammation is one of the phenomena associated with diabetes and omega-3 fatty acids can slow down the process of inflammation. In this research, we investigate aerobic exercises with omega-3 supplementation on the levels of TNF-?, IL-1 and insulin resistance in men with type 2 diabetes. Due to increasing age, obesity and inactivity, consumption of more simple sugars and high-calorie foods, this disease has become increasingly prevalent, so that according to the prediction of the World Health Organization, the number of adults with diabetes is expected to reach 300 million people in 2025 (22). There are two types of diabetes, type 1 diabetes, which accounts for 5-10% of diabetics, is insulin-dependent and is caused by a defect in insulin production by pancreatic beta cells. Type 2 diabetes is a combination of metabolic syndrome (vascular inflammation, endothelial dysfunction, high blood pressure, dyslipidemia, and visceral obesity) and its pathophysiology is a result of the complex conflict between insulin resistance, defects in the action of beta cells and adipokines (23). Insulin resistance exists in 90% of people with type 2 diabetes, and research shows that 80% of these people are obese and the remaining 20% ??are thin people (24).

It is believed that the immune system has evolved as a tool to recognize internal cells from foreign substances and maintain body homeostasis (25). The body's ability to recognize and fight countless invaders is incredibly complex. In fact, all the body's defense responses against new and foreign molecules take place in the immune system (18). These foreign factors include immunogenic proteins, viruses, bacteria, fungi and parasites, cancer growth, transplanted tissues. In order to produce an immune response against any foreign agent, a complex cooperation between cells, tissues and intermediate molecules of the body is needed (26). In the past, adipose tissue in the body was considered as a source of fat storage, but now this tissue is referred to as an active endocrine organ that secretes many hormones known as adipokines (27). Some of these soluble mediators that play an important role in the functioning of the body's immune system include cytokines (a heterogeneous group of growth and regulatory factors), complements, acute phase proteins, and antibodies (28). The term cytokine refers to a group of general regulatory protein factors that include lymphokines made from lymphocytes and monokines made from monocytes (29). Cytokines are primarily growth regulatory factors, but they may also have other functions such as playing a role in inflammatory responses (30). Cytokines are not only released following pathological stimuli such as infections or muscle injuries, but also produced in response to physiological stimuli such as heavy activities, hormonal pressures, energy crisis and oxidative stress(31). Cytokines are divided into two major groups: pro-inflammatory and anti-inflammatory. The main inflammatory cytokines include INF-g[1], TNF-?[2], 8IL-, 6IL-, 2IL-, 1 IL-b[3]. On the other hand, the most important anti-inflammatory cytokines are ar1-IL, 4-IL, 5-IL, 10-IL and 13-IL (32). Anti-inflammatory cytokines directly inhibit the production of inflammatory cytokines (33).