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EFFECT OF EXERCISE INTENSITY ONGLUCOSE AND INSULIN METABOLISMIN OBESE INDIVIDUALS AND OBESE NIDDM PATIENTS
DIPAK CHATTERJEE
Sr. Physiotherapist, Head of Deptt. SL Raheja Hospital, All India Institute of Diabetes, Mahim, Mumbai 400 016.
The primary purpose of this article was to Evaluate the acute effect of exercise of different intensity on plasma glucose and insulin responses.
Regular exercise can improve glucose tolerance, decrease plasma insulin and improve the lipid profile in obese individual. Some benefits of exercise may be related to a change in body fat mass (specially increased fat) although there also seems to be an independent effect.
Exercise improves insulin sensitivity. This may be of particular value to individuals with insulin resistance, such as those who are obese or those who have NIDDM. The improvement in insulin sensitivity does not necessarily require a long interval of physical training. Devlin and Horton and Devlin et al, have found that a single bout of exercise was effective in improving insulin-mediated intracellular glucose disposal. Cononie et al and Regers et al have also shown that 1 week of daily exercise reduced plasma insulin concentrations after glucose ingestion. All of these studies, however, used fairly vigorous exercise protocols that are of moderate to high intensities (i.e. 70-85% Vo2max). Many obese individuals, whether with NIDDM or glucose-tolerant, are sedentary, and this raised the question of whether they would be either willing or able to participate in a moderate to high-intensity exercise programme. Therefore, if similar effects on glucose tolerance and insulin sensitivity could be achieved at a low intensity, this would be a more practical approach.
The present study was undertaken to test the hypothesis that 1 week of daily low-intensity exercise, if performed long enough in each session to expend the same amount of calories as a shorter session of higher intensity exercise, would have equivalent efficacy in improving glucose tolerance and insulin sensitivity among obese individuals and in those with NIDDM. Using the glucose clamp technique, Bogardus et al and Devlin et al have postulated that the acute improvement of insulin sensitivity depends upon partial depletion of muscle glycogen. Muscle glycogen is more apt to be used during moderate to high intensity exercise compared with low intensity exercise. Thus, despite adjustment of the duration of exercise to achieve a similar amount of energy expenditure during low-intensity exercise compared with moderate to high-intensity exercise, the relative contribution of muscle glycogen utilization to the total energy production might differ. Therefore, a secondary goal was to assess muscle glycogen utilization to determine the potential role this might have for exercise induced changes in insulin action among obese individuals with and without NIDDM.
Non insulin dependent diabetes mellitus, more correctly termed as Type 2 diabetes of adulthood is reaching epidemic proportions in developed nations and in developing countries as well. In the US today there are nearly 12 million diabetics with 1 out of every 15 being afflicted by the disease of high complications and mortality. In India, there are nearly 40 million diabetics and by the year 2025 India will have a mind boggling figure of 57 million diabetics. That is 3 out of every 15 Indians will have the disorder. WHO estimates that there will be nearly 120 million diabetics in the world by 2005.
Type 2 is the commonest form of diabetes characterized by disorders of insulin secretion and insulin action. Both these abnormalities are usually present at the time the diabetes is clinically manifest. These diabetics are at high risk for cardiovascular disorders (CVD). Another form of ‘potential diabetes’ is termed as ‘Insulin Resistance Syndrome’ or ‘Metabolic Syndrome’ which are both diagnostic and therapeutic challenge, and is characterised with hypertension, central (upper body) obesity, dyslipidaemia with or without hyperglycaemia. These individuals who are at high risk for CVD are in the increase in the metropolitan cities of the world because of the altered life style, lack of physical exercise, food intake and general stress associated with an affluent life. Evidence is now accumulating that insulin resistance may be common aetiological factor for the syndrome.
The rise in the figures of the patients with type 2 diabetes or Metabolic syndrome in the world is now known to be related to the increased obesity in the industrialised nations. Surveys show close association between type 2 diabetes and increased central or visceral distribution of fat. The body mass index (BMI) is now considered to be a good indicator of obesity. According to WHO, a BMI value of 25-29.9 was considered as overweight and BMI > 30 as obese. Nearly 30 to 40% of the population of Europe and Australia have a BMI > 25. Report or surveys have clearly suggested that the risk factors for type 2 diabetes include the (i) extent of obesity (ii) duration of obesity (iii) central or visceral obesity (iv) inactivity (v) High-fat diet (vi) hyperinsulinaemia, insulin resistance and (vii) impaired glucose tolerance. Many surveys and studies conducted in the West indicate positive association BMI with type 2 diabetes.
Obesity : The second National Health and Nutrition Examination Survey in the US observed that the relative risk of diabetes for overweight adults was nearly 2.9 times that for the non-overweight adults. The relative risk imposed obesity in young adults (30-45 years) was 3.8 times that of the non-overweight match control. Another survey in USA showed men in BMI range of 25-26.9 had 2.2 times higher risk for type 2 diabetes than those with BMI < 23. The risk increased with increasing BMI with men in BMI group > 35 having a relative risk of 42.1 times greater than men with BMI < 23.
A British study showed that men in the upper fifth of BMR range (> 27.9) had a risk factor 7 times more than those in the lowest.
The findings for women are quite similar, not only the age adjusted relative risk increase with increased BMI value, excess risk was seen in women in the upper end of normal BMI (< 22.9) range, From a risk of 1.0 at BMI of < 22 the risk rose to 2.9 at BMI of 22-22.9 and a whopping 93.2 at BMI of > 35.
Weight Gain : BMI along with weight gain is an important risk factor for diabetes. A Health Professionals follow up study which considered varying parameters including BMI showed that men who gained weight > 13.6 kg over a 5 year term had 4.5 times higher risk than men whose weight remained within 4.5 kg of their weight at entry. Across the range of BMI, weight gain was positively correlated with risk for diabetes. Among women, those whose weight increased from 5 to 7.9 kg during the 14 year period of study had a risk of 1.9 times that of men who did not gain weight. The risk was considerably reduced when they lost weight.
Duration of obesity : The longer one stays obese greater is their risk for developing type 2 diabetes. In a study those who were at a BMI 30 for > 10 years had a risk twice that of women who had been obese for less than 5 years.
Body fat distribution : The pattern of body fat distribution is also a contributory factor for type 2 diabetes. Studies reveal that persons with central or visceral obesity or the android pattern of obesity are more likely to develop diabetes. Another factor that appears to identify likely type 2 diabetes individuals is the waist-hip (W/H) ratio and upper body adiposity. A study in Mexican-American men and a 13.5 year study of nearly 800 Swedish men showed that W/H ratio was positively associated with diabetes independently of BMI. Recently, a good correlation has been noted between waist circumference and type 2 diabetes particularly in those with a high W/H ratio.
However, an unique standard for detecting excessive visceral deposition is computed tomographic scanning. A Japanese study using this technique showed that visceral fat deposition was more closely associated with type 2 diabetes than subcutaneous fat in the abdomen. The subcutaneous fat deposits in the abdomen, thorax or thigh did not show any significance as predictors.
Food Intake : Since obesity is an important predictor of type 2 diabetes a caloric intake in excess of body need is a risk factor. Dietary fat, particularly saturated fat, is a dietary factor that is important link between obesity and diabetes. In rats insulin resistance develops with increased fat intake. Such a feature must be valid for humans as well.
Lack of Physical Activity : A British Regional heart study noted that men who were occupationally or habitually used to appreciable physical activity were at low risk for diabetes compared to inactive individuals. High levels of physical activity are associated with lowered plasma insulin levels and physical training lowers insulin resistance.
BIOCHEMICAL UNDERSTANDING OF HOW OBESITY IS LINKED TO DIABETES
Visceral or Central distribution of fat is responsible for the breakdown of normal glucose homoeostasis. This causes increased availability of free fatty acids (FFA) and increased oxidation of FFAs, increased hepatic glycolysis and glucose release and peripheral insulin resistance.
Hyperinsulinaemia and insulin resistance are positively correlated not only to increasing BMI but also to the amount of visceral fat.
Glucose fatty acid cycle : A factor of significance in initiating and maintaining the evolution of obesity to diabetes, as mentioned earlier, is increased availability of FFA and its oxidation which block the peripheral action of insulin as well as affects the oxidative and anaerobic pathway of glucose metabolism. It also brings about impairment of glucose utilisation. Increased plasma FFA levels increase liver glucose release adversely affect glucose uptake by peripheral tissue and causes insulin resistance.
The biochemical features can be summed up as follows:
Besides the dominant role of obesity in type 2 diabetes induction, genetic predisposition is also a factor to be considered. There is a strong link between diabetes and family history. A US study reveals that if one member of a family has diabetes another member’s chance of the disease is doubled and it is quadrupled if 2 family members have the disease.
Ethnicity has also a role in diabetes. In US the black have a higher incidence of diabetes then the white. The correlation between obesity and insulin resistant diabetes is very strong in Hispanies than in whites. However, data suggest that genetically disposed individuals are not always a victim. Environmental factors also have a role to play.
Gene : No single gene for type 2 diabetes has been identified except for the maturity onset diabetes of the young (MODY). Other gene include those coding for glucokinase insulin and insulin receptor.
Central Obesity Increased FFA Increased FFA Availability Increased FFA disposal/Oxidation Decreased Lipoprotein Lipase Increased Lipid Oxidation Increased serum triglycerides Increased VLDL Decreased HDL Increased LDL Oxidation---
i) Decreased glucose oxidation and storage ii) Impairment of insulin mediated inhibition of hepatic glucose release Impaired Glucose Tolerance Loss of Hepatic insulin sensitivity More and More lipidoxidized Less and Less glucose oxidized and stored
Paediatric Factors
Low birth weight and low weight gain during the first year of life are associated with the occurrence of type 2 diabetes, blood pressure and hyperlipidaemia and central obesity many years later in adult hood.
Factors that can prevent or treat type 2 Diabetes
Weight loss even to modest extent can reduce considerably an obese individual’s risk for type 2 diabetes, can improve diabetic control as well as reduce or eliminate the use of hypoglycaemic agents. The Nurses’ Health Study showed that women who lost more than 5 kg over a 10 year period reduced their risk for diabetes by 50%.
Control of Hyperglycaemia
A study of UK Prospective Diabetes study showed that more a diabetic patient lost weight, greater was the improvement in blood glucose control. To lower blood glucose to a normal level an average weight loss of 18 kg was needed.
CAN GENETIC PREDISPOSITION BE OVERCOME?
The fact that type 2 diabetes does not inevitably occur in both of a pair of monozygotic twins clearly indicates that environment, as well as heredity, has a part to play in the development of type 2 diabetes. Furthermore, since type 2 diabetes is not, in many cases, a monogenic disorder, the interaction between genetics and environment is likely to be complex and variable from individual to individual. Genetic differences may explain in part why, for example, some patients with type 2 diabetes achieve improved glucose control through weight loss and/or exercise and others do not.
There is every reason to suppose that manipulation of the metabolic environment through weight loss should be able to prevent, or at the very least delay, the development of diabetes, even in people with a strong genetic predisposition. A study in a monkey model with a genetic predisposition towards diabetes has shown that the development of diabetes can be postponed - possibly indefinitely - by the simple strategy of preventing the weight gain usually encountered in older adults.
The findings for women are very similar to those for men. The Nurses’ Health Study followed more than 110,000 women for 14 years, from an age of 30 to 55 years at entry. BMI was again found to be the dominant predictor of risk for type 2 diabetes. Not only did age-adjusted relative risk increase with BMI, excess risk was also found among women towards the upper end of the ‘normal’-weight range. For a relative risk of 1.0 at a BMI of < 22, the risk rose to 2.9 at a BMI of 22-22.9, and a staggerring 93.2 at a BMI of ô 35.
IMPORTANCE OF WEIGHT GAIN
Weight gain, in addition to BMI, is also a strong risk factor for diabetes. For example, in the Health Professionals’ Follow-up Study, after controlling for BMI at entry, family history, age and smoking, men who gained > 13.6 kg over the 5 years of the study had a risk 4.5 times greater than that of men who remained within 4.5 kg of their weight at entry. Across the range of BMI, absolute weight gain was positively associated with the risk of diabetes. Risk increased within each tertile of weight gain as well as within each category of BMI at age 21.
In the Nurses’ Health Study, the relative risk among women who had a weight gain of 5.0-7.9 kg. over the 14 years of the study was 1.9, compared with that of women whose weight did not change. The relative risk of those who gained 8.0-10.9 kg was 2.7. Women who lost weight reduced their risk.
Obesity is probably the most important modifiable risk factor for type 2 diabetes (Table 1). The US National Commission on Diabetes reported that the risk of developing type 2 diabetes was about two fold in mildly obese, fivefold in moderately obese and tenfold in severely obese people.
TABLE 1
Risk factors for type 2 diabetesModifiable Obesity
Duration obesity
Visceral obesity
Inactivity
High-fat diet
Hyperinsulinaemia and insulin resistance
Impaired glucose toleranceNon-modifiable
Genetic background
Age
Gender
Similarly, the second National Health and Nutrition Examination Survey (NHANES II) in the US found that, for adults self-categorized as overweight the relative risk of diabetes (diagnosed on a two hour glucose tolerance test) was 2.9 times that for non-overweight people of a similar age. The relative risk imposed by obesity was highest among younger people (20-45 years) whose risk was 3.8 times that for their non-overweight compatriots. However, overweight Americans aged 45-75 years still had about twice the risk of non-overweight individuals.
PROSPECTIVE STUDIES
Confirmation of the risk between obesity and type 2 diabetes comes from recent prospective studies. The British Regional Heart Study in which 7,735 British middle aged men were followed up for a men of 128 years, found BMI to be the dominant risk factor for type 2 diabetes.8 Multivariate analysis showed that men in the upper fifth of BMI range (> 27.00) had more than seven times the risk of type 2 diabetes, compared with those in the lowest fifth. However, this does not mean that diabetes was confined to the severely obese over 75% of cases occurred in men with a BMI of < 30. Other factors associated with type 2 diabetes included low levels of physical activity, high serum tryglycerides, low HDL cholesterol, high heart rate, high uric acid concentration, and existing coronary heart disease.
The US Health Professionals follow-up study in 51,529 men (followed up for 5 years from the age of 45 to 75 years) also found a strong positive association between BMI and risk of developing diabetes. Men with a BMI of 25-26.9 (i.e. only mildly obese) had a risk 2.2 times.
The relation between exercise-induced reduction in muscle glycogen and improved insulin sensitivity can be confounded by the diet consumed during the post exercise period. Young et al showed that in rats, post exercise carbohydrate feeding facilitated muscle glycogen repletion and thus speeded reversal of enhanced glucose uptake in muscle after exercise. Ivy et al also demonstrated that either a high or low-carbohydrate diet consumed after exercise counteracted exercise-induced improvement in insulin sensitivity. In the present study, the confounding effect of post exercise diet on improved insulin sensitivity was minimised in that the total caloric intake was consistent and the total carbohydrate intake ranged from 245 to 271 g/day during the day before each OGTT.
In the present study substrate utilization during exercise was also assessed in obese and obese NIDDM subjects. Substrate metabolism during exercise is an aspect of fuel homoeostasis about which there are relatively few data concerning NIDDM. Despite differences between NIDDM and nondiabetic subjects in glucose homoeostasis at rest and despite some persistent differences in substrate and insulin concentrations during exercise, there was considerable similarity in oxidation, lipid oxidation, plasma glucose utilization, and muscle glycogen utilization. These findings suggest that mechanisms that govern substrate utilization during exercise appear to compensate for insulin resistance, hyperglycaemia and elevated plasma FFA concentrations such that the pattern of substrate utilization is comparable with that in nondiabetic subjects. This conclusion is supported by animal studies showing that exercise-stimulated glucose transport is normal in insulin-resistant obese Zucker rats.
In conclusion the present study demonstrated that 1 week of daily exercise at 70% Vo2 peak for 50 min improves insulin sensitivity in obese individuals with normal glucose tolerance. However, this improvement did not occur after 7 consecutive days of exercise at 50% Vo2 peak for isocaloric duration. The improvement in insulin sensitivity in obese subjects that occurred with short-term moderate intensity exercise may be related to greater muscle glycogen utilization during exercise. In obese NIDDM subjects who are relatively hypoinsulinaemic, no improvement in glucose tolerance or insulin sensitivity was sustained despite patterns of exercise induced substrate utilization and energy expenditure that were very similar to obese nondiabetic subjects. Further studies are needed to determine whether long-term exercise-induced improvements in insulin sensitivity are also dependent upon including exercise of sufficiently high intensity to periodically deplete muscle glycogen.
ACKNOWLEDGEMENTS
I thank Dr. AP Banerjee Ex Senior Scientific Officer, Cancer Research Institute, Parel, Mumbai, for his assistance and guidance, useful suggestion in the preparation of this manuscript.
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