Insulin resistance can cause an abnormal ratio of high-density lipoproteins (HDL) to low-density lipoproteins (LDL). HDL’s remove excess lipids from the arterial wall and transport it to the liver, whilst LDL’s transport lipids from the liver to the tissues. The syndrome results in a reduced ratio of HDL in relation to LDL because the insulin has less effect on inhibiting the free fatty acids release from the adipocytes. This increases the amount of free fatty acids in the blood and to compensate the liver repackages the lipids into LDL’s. Reaven (1993) also stated that the resistance to glucose stimulated uptake leads to an enhanced hepatic very low-density (VLDL) triclycerides. These LDL’s and VLDL’s increase the likelihood of the development of fatty plaques and their levels are a good indicator of coronary heart disease. Another factor is that low-density lipoproteins have a similar structure to plasminogen. Plasminogen is an anticoagulant, which binds to the receptor cite on fibrin in order to dissolve the blood clots. Therefore because of the similar structure the lipoprotein competes with plasminogen for the receptor cites and results in the decreased action of fibrin. Fibrinolysis is inhibited and therefore there is an increased chance of blood clots. These factors combine to stimulate clots and increase the risk of developing coronary heart disease. Evidence of this relationship is found in a study conducted by Lamarche et al., (1995, cited in Despres, 1997). The research examined the development of ischemic heart disease in relation to the prevalence of a dyslipidemic state. The results found that 50% of the men who did not develop heart diseases had normal lipoprotein lipid profile, whereas, two thirds of the men who developed ischemic heart disease had abnormal lipoprotein concentrations.
An insulin resistant state is also associated with visceral obesity and this may lead to glucose intolerance and could develop into Type II diabetes. Despres (1997) stated that visceral obesity is a permissive factor that exacerbates an individual’s susceptibility to insulin resistance and coronary heart disease. It is also associated with a state called dyslipidemia, which includes low HDL cholesterol levels and an increased proportion of small dense LDL particles (Despres 1997). Further research has concluded that a relationship exists between an increase in a dyslipidemia state and an increased risk of coronary heart disease.
- The mechanisms by which exercise prevents insulin resistance and therefore reduces the risk of the associated pathologies.
It is has been found in part (ii) that insulin resistance causes hypertension, diabetes, obesity and coronary heart disease. But rather than treating these symptoms it is more beneficial to treat the cause of the symptoms i.e. insulin resistance. Studies have shown that physical activity has a beneficial effect on insulin sensitivity in normal populations but more important to this study it has been found to beneficial to those people who are insulin resistant.
It is seen that insulin sensitivity has a negative correlation with age, but a recent study conducted by Seals et al., (1984, cited in Borghouts and Keizer, 2000) found that endurance trained elderly subjects are more insulin sensitive than young, sedentary subjects. So although age is a discriminating factor it is therefore better to be old and physically active than to be young and inactive. Evidence from epidemiological studies suggest that by increasing the frequency of exercise from under once a week to just a least once a week can result in a significant decrease in the incidence of non-insulin dependent diabetes mellitus (NIDDM). From figure 1 it is evident that the greatest fall is from this initial increase in exercise and that a further increase in frequency results in a related drop in incidence, although the fall is not as large.
Figure 1 Incidence rates of NIDDM in relation to
frequency of vigorous exercise.
This highlights that important benefits of exercise and furthermore that the increase in exercise frequency does not have to be dramatic to produce significant effects. There have also been more in-depth, cross sectional studies that have compared athletes to non-athletes. The results have shown that the trained subjects are more insulin sensitive than untrained subjects (Borghouts and Keizer 2000)
Now that is has been identified that exercise is beneficial to insulin resistance an important factor to consider is whether it is the acute effects of exercise or the adaptations over an exercise regime. For example in figure 2 it can be seen that glucose disposal is initially higher in trained subjects rather than untrained subjects. But when the investigation was continued it was found that from 4 days after the exercise the removal became the same in both trained and untrained subjects, showing that the effect of the exercise was only acute.
Figure 2 Changes in glucose disposal during detraining in
trained and untrained individuals.
It has also been found that an acute bout of exercise is more beneficial in trained subjects than in untrained subjects. A study examined the glucose uptake over the leg in trained and untrained legs. The test took place on a bicycle ergometer and insulin stimulated glucose uptake was measured 16 hrs after the exercise bout (Borghouts and Keizer 2000). The research found that there was increased uptake in the trained leg but not in the untrained leg. Evidence has shown that acute exercise increases the activity of glycogen synthase, which results in increased glycogen formation.
A long-term effect of training is an improvement to glucose homeostasis due to improvements in peripheral responses. Training increases muscle capillary density in sufferers of non-insulin dependent diabetes mellitus and also increases glucose transport and metabolism. This along with the increased muscle blood flow will result in an increase in the supply of glucose. The transport capacity of the glucose is also affected by the amount of glucose transporters. Therefore an important factor is the amount of GLUT4 and it is seen that the long-term physical training can affect this protein. In endurance trained athletes the number of GLUT4 in the skeletal muscle is increased in NIDDM patients. It has also been suggested that exercise can increase the number of insulin receptor binding cites, which therefore increases the chances of hormone receptor interaction.
Now that the treatment of insulin resistance has been examined it is important to observe how exercise can benefit the associated pathologies that result from the disease. Due to the fact that obesity has been identified as an associated pathology it can be assumed that for a proportion of insulin resistance sufferers performing any aerobic activity will be difficult. It is therefore vital to highlight resistance training as an important factor for obese people in their fight against insulin resistance. The resistance training is crucial as it increases muscle mass and strength and therefore increases the capability of the person to do exercise. A body composition high in muscle mass and low in body fat is vitally important for insulin stimulated glucose uptake (Borghouts and Keizer 2000). The training can also increase the number of insulin receptors and therefore has a combined effect of increasing the insulin sensitivity of the individual. In addition to this, evidence has been found by Devlin et al., (1987, cited in Borghouts and Keizer, 2000), which states that a single bout of high-intensity exercise had a significant effect on insulin stimulated glucose uptake in obese subjects. Exercise is an important variable in understanding and treating obesity because it is the principal component of energy expenditure. Studies have found that total fat loss is greater with exercise and a diet, than with the diet alone. The research in this area has been limited but it has shown that with exercise there was a significant decrease in visceral adipose tissue. This in turn results in a reduction in free fatty acid levels, which are increased in NIDDM sufferers and can hinder glucose uptake and metabolism. But research also showed no significant difference in the subcutaneous adipose tissue and a suggested reason for the conflicting results is that the energy expended during the exercise period causes a fatigue induced drop in daily activity levels. Therefore total activity levels are the same with and without exercise. Ivy (1997) stated that epidemiological studies has shown that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose intolerance and NIDDM than individuals that are physically inactive.
Sustained exercise can also benefit coronary heart disease (CHD), which is another pathology that occurs as a result from insulin resistance. Hardman (1996) stated that physical inactivity is a strong factor in the risk of CHD and that in 1991 this disease accounted for 29% of all deaths in males and 23% of all deaths in females in England. Exercise increases the adequacy of cardiac output and the efficiency of the respiratory system. After several weeks of training, a healthy person increases maximal rate of oxygen delivery to the tissues. Oxygen delivery rises because haemoglobin level increases and skeletal muscles develop more capillary networks in response to long-term training.
Powell et al, (1987, cited in Dishman, 1994) in an extensive review, concluded that studies employing the best epidemiological research methods tended to observe an inverse relationship between the amount of habitual physical activity and coronary heart disease risk. Evidence to confirm this, was found in a recent report by Morris, Everitt, Pollard, Chave and Semmence (1980, cited in Dishman, 1994). The report was on males who had been asked to complete a detailed record of their physical activity at the weekend, which was used to classify the men into two categories, vigorous and non-vigorous exercisers. Vigorous exercise was defined as exercise at a level equal to heavy industrial work and the study showed that 20% of the participants were classified as vigorous exercisers. The men were then followed for mortality and it was found that there were 475 deaths from coronary heart disease. It concluded that the death rate was twice as high in non-vigorous exercisers than in vigorous exercisers.
To conclude it can be seen from this essay that exercise is beneficial in the improvement and prevention of insulin resistance. This is essential as it has been highlighted that many associated pathologies can stem from insulin resistance. It has also been highlighted that exercise is beneficial in the treatment of these symptoms and can therefore lead to a better way of life for insulin resistance sufferers. A final point that has been discussed is that for an improvement to take place the amount of exercise does not have to be dramatic (once a week) and so anybody can do it.
References:
Borghouts, L.B. and Keizer, H.A. (2000). Exercise and Insulin Sensitivity: A Review. International Journal of Sports Medicine, 20, pp 1 –12.
Defronzo, R.A., Ferrannini, E. and Kovisto, V. (1983). New concepts in the Pathogenesis and Treatment of Non-Insulin Dependent Diabetes Mellitus. American Journal of Medicine, 74, pp 52-81.
Despres, J.P. (1997). Visceral Obesity, Insulin Resistance, and Dyslipidemia: Contribution of Endurance Exercise Training to the Treatment of the Plurimetabolic syndrome. In Exercise and Sports Science Reviews (edited by J. Hollosey), pp. 271-300. William/Wilkins.
Dishman, R.K. (1994). Advances In Exercise Adherence. Illinois: Champaign.
Ferrannini, E. and Natali. A. (1991) Essential hypertension, metabolic disorders, and insulin resistance. American Heart Journal, 121, pp 1274- 1282.
Hardman, A.E. (1996) Exercise in the prevention of atherosclerotic, metabolic and hypertensive diseases: A review. Journal of Sports Sciences, 14, pp 201-218.
Ivy, J.L. (1997). Role of Exercise Training in the Prevention and Treatment of Insulin Resistance and Non-Insulin-Dependent diabetes Mellitus. Journal of Sports Medicine, 24, pp 321-336.
Reaven, G.M. (1993) Role of Insulin Resistance in Human Disease (Syndrome X): An Expanded Definition. Annual Rev Medicine, 44, pp121-131.
Simoneau, J.A. and Kelley, D.E. (1997) Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. Journal of Applied Physiology, 83(1), pp 166-171.