Acta med. scand. Vol. 192, pp. 439-443, 1972

EFFECTS OF PHYSICAL TRAINING ON GLUCOSE TOLERANCE, PLASMA INSULIN AND LlPIDS AND ON BODY COMPOSITION IN MEN

AFTER MYOCARDIAL INFARCTION

Per Bjorntorp, Peter Berchtold, Gunnar Grimby, Bjorn Lindholm, Harald Sanne, Gosta Tibblin and Lars Wilhelmsen

From the First Medical Service and the Department of Rehabilitation Medicine I , Sahlgren’s Hospital, University of Gotheribrrrg, Goihenburg, Sweden

Abstract. Every second of non-selected men below the age of 55 years who had survived a myocardial infarc- tion was placed in a group for physical training, while each other constituted a control. The physical training program was selected according to each patient’s indi- vidual maximal working capacity and lasted for 9 months, beginning 3 months after the myocardial infarction. At the end of the training period the experimental group was subdivided into one group of adequately trained patients and one consisting of drop-outs and patients with poor adherence. The patients who followed the program in- creased their physical work performance. In this group a decrease was found in plasma insulin values after a glucose tolerance test, a slight increase in glucose tolerance and a decrease in body fat and plasma triglycerides. Body cell mass and plasma cholesterol did not change. The men selected for the training program, but who were not able to follow it sufficiently, as well as the controls, showed a less marked decrease in plasma insulin values a t reexamination.

In relation to the large number of studies con- cerned with effects on plasma lipids of changes in the quality and quantity of caloric intake the interest in the effects of energy output changes has been much less. In healthy individuals physical training apparently produces minor or no changes in plasma cholesterol (6, 11, 18, 19, 20, 25, 29), while plasma triglycerides are lowered to 22-40 76 (14, 18, 29). This decrease is of the same order as that observed after acute prolonged exercise (8). In patients with cardiovascular disease plasma cholesterol has been found to decrease moderately after physical training (27). The present paper describes the effect of physical training on body composition, plasma insulin and lipids, and glucose tolerance, in men who have survived a myocardial infarction.

MATERIAL AND METHODS

The material of myocardial infarction patients has been described in detail previously (2). Briefly it consists of all men below the age of 55 years who have suffered a myocardial infarction and survived in the city of Gothen- burg, Sweden, irom 1 January, 1968, through 31 May, 1969. Every second of these 104 men was selected for a physical training program. The remaining 52 patients constituted the non-training group.

When discharged from the hospital after the myocardial infarction the patients were given similar instructions. They were recommended to avoid bed rest. Obvious dietary abnormalities were corrected by a dielicinn towards a diet similar to a Swedish normal diet (5).

At the beginning of the training period rcpeated exercise tests were performed on an electrically braked bicycle ergometer with stepwise increasing work loads, 4 min at each step, up to “maximal” exercise. The exercise was interrupted due to general fatigue, angina pectoris, ECG changes, poor BP regulation or loconiotor symptoms. Excrcise tests were also performed during the training period in order to direct the training intensity. One year after the myocardial infarction all patients were re- examined. The training consisted of an interval program of cycling, running and calisthenics for i/2 hour three times a week during 9 months under the supervision of a physiotherapist and a physician. The heart rate during the heavy intervals was on an average 146 2 16 beats/min (range 109-164). On the day determined for examination of the effects of the procedures (31 May 1969) 32 of the patients originally selected had been reexamined one year after the infarction. Only 15 of them had adhered adequately to the physical training program and had reached the prescribed pulse rate during the different exercises. The remaining 17 could not follow the program in a sufficient way. The physical work capacity-in terms of reduced heart rate at a submaximal work load or the maximal achieved work load (Table 1)-increased significantly in the first mentioned group, while this WBS not the case for the group which did not follow the training program sufficiently. At the same date 26 of the

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440 P . Bjorntorp et al.

Table I. Results from exercise tests in the myocardial infarction patients (mean and S. E M . )

HR at HR at highest 4 min Highest work

Months 400 kpm/min work load load after onset n beats/min n beats/min n kpm/min

Non-training 3 37 116+_3 37 129+_4 19 672+61 12 17 114+5 20 12725' 23 601261

Insufficiently trained 3 16 111+4 17 14128 16 756k63 12 15 112f4 17 14257' 17 799i74

Training 3 14 11124 15 15625 15 882266 12 15 1 0 3 i 2 14 144+5' 15 1146k70

' At the work load, which was the highest 4 rnin work load, 3 months after onset.

non-training men with myocardial infarction had been reexamined.

The control group consisted of 76 randomly selected 55-year-old men from Gothenburg. These men have previously been presented in detail (4). The maximal oxygen uptake in this population was 2.3 I/min (15), corresponding to a maximal work load of about 1000 kpm/min.

Metabolic examinations were performed 3 and 12 months after the myocardial infarction, i.e. before and

after the period of physical training. The patients were instructed to report to the laboratory after restricted physical activity and after having fasted and abstained from smoking for 12 hours before the investigation. Venous blood was first collected in chilled heparinized tubes for determination of blood glucose (21), plasma insulin (16), cholesterol (9) and triglycerides (7). After oral intake of 100 g glucose, blood glucose and plasma insulin were determined at 30, 60, 90 and 120 min.

On another occasion body composition was deter-

Table 11. Results in patients who have suffered a myocardial infarction (MI) and in controls (mean and S. E.M.)

Group

Months Insulin (pU/ml) Sum of after insulin onset n 0 rnin 30 min 60 rnin 90 min 120 rnin values

Controls 76 1021 79+6 9 5 2 9 96+12 55f6 337229

MI, non-training 3 52 12+1 93kIO 105k12 108k14 93f14 411+45 12 26 12+3 57k7 80+11 100+24 87f25 336 k 64

MI, insufficiently trained 3 17 1523 76f21 92+15 106$20 78+15 367 2 58 12 17 9+1 45+7 5 8 i l O 5 9 2 9 48f7 219230

MI, training 3 15 1 3 2 2 Elk17 152f26 187f51 134224 5661-99 12 15 8 j l 4 0 2 6 51 +_7 52&7 4518 196+23

Table 111. Comparisons between results 3 and 12 months after discharge in patients with myocardial infarc- tion ( M I ) physically trained, insufficiently trained and non-training during this period (p-values of analysis of paired differences)

Group

Insulin (pU/ml) Sum of insulin

n 0 min 30 rnin 60 min 90 min 120 min values

MI, non-training 26 n s . < 0.01 < 0.01 n.s. < 0.05 < 0.01

MI, trained 15 <0.01 < 0.05 < 0.001 <0.01 < 0.001 < 0.001 MI, insufficiently trained 17 n s . n.s. < 0.05 0.05 < 0.05 .< 0.05

Acta med. scand. 192

Physical training after myocardial infarction 441

RESULTS

Table I1 shows the metabolic and body composi- tion values of the different groups. As described previously ( 2 ) , the myocardial infarction patients had at 3 months after myocardial infarction a somewhat higher insulin value only at 120 min in comparison with controls of the same age ( p < 0.02). Glucose tolerance was decreased (higher glucose values at 0, 90 and 120 rnin and sum of glucose values, p < 0.01). Triglycerides and cho- lesterol were higher ( p < O . O 2 ) , but body fat was not different .

Table 111 shows the changes during the 9 months between the first and second examina- tion in non-training, insufficiently trained and in the physically trained patients with myocardial infarction. Plasma insulin decreased on several points in non-training and insufficiently trained patients, but the decrease was more pronounced in the trained group. Glucose tolerance did not

DISCUSSION

The insulin values were lower after physical training. I t is probable that this difference is somewhat overestimated because of the fact that a few patients with very high insulin values be- longed to the physically trained group. This is suggested also by the lack of difference between the trained and insufficiently trained patients at 12 months after the onset. There were several differences, on the other hand, between the non- trained and the trained group at the end of the training period (Table 11). This supports the con- clusion that physical training really had an effect on insulin values. Physical training also caused a decrease in body fat and plasma triglycerides and a slight improvement of glucose tolerance.

It is not clear which factor within the concept of “physical training” is active in producing the described changes. An acute work load causes a decrease of plasma triglyceride during a limited

Glucose (mg/100 ml)

Omin 30 min 60 min 90min 120 min

Sum of glucose values

Body cell Triglycerides Cholesterol Body fat mass (rng/100 ml) (mg/100 ml) (kg) (kg)

6 4 f l 1 2 1 j 3 l08+5 86+4 69+3

72+2 124_+4 119+6 10526 9 1 k 6 73+3 127+7 12429 111+9 94+ 10

77+3 1 2 7 j 6 130+10 122+10 104+7 70+3 l l 5 j 5 120k7 l05+9 92+8

7 7 f 4 140210 160f15 140216 110+14 74$-4 136+9 135+13 104+11 88+10

448k 14

503 + 21 524 f 34

547 + 28 503 t 26

621 + 56 573 + 42

1 0 9 j 7 257 j 5 1 6 j l -

135+14 261+10 1 3 k 2 -

149215 275 + 8 3651 3 0 t l 120+16 261k12 13+2 29+2

161 _+ 15 281+10 15+1 30k1 92+8 276+8 l o t 1 3 2 2 1

15228 276+1 1 5 2 1 -

Glucose (mg/100 ml) Sum of Body cell glucose Triglycerides Cholesterol Body fat mass

0 rnin 30 rnin 60 rnin 90 rnin 120 min values (mg/100 ml) (mg/100 ml) (kg) (kg)

n s . n.s. n s . n.s. n.s. n.s. n.s. n.s. n s . n s . n.s. n.s. n s . n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. c0.05 n s . n.s. < 0.001 n.s. < 0.01 n.s.

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442 P. Bjorntorp et al.

period of time (8, 18). Acute work also produces a blood glucose lowering factor in working muscle (13). In obesity the effect on plasma in- sulin lasts for at least 4 days (10). It cannot be excluded that the effect of the last working period during the physical training program was responsible for at least some of the measured ef- fects on plasma insulin and triglycerides.

Physical training, however, also produces several more long-lasting adaptive changes in the or- ganism. A decreased body fat most probably would cause a decrease in plasma insulin, because these factors are statistically intimately associated (1, 4, 28). A decrease of insulin after physical training can, however, occur in obese persons without a decrease in body fat (3). The working muscles also show enzymic adaptation both in rat (17) and man (30). This adaptation includes an increase in the capacity of the aerobic enzyme system. It is of interest that after training there is a more pronounced decrease in plasma tri- glyceride after acute work in physically trained men or rats than in the untrained (12, 19).

Physical training caused a decrease in plasma insulin and triglyceride concentration, some im- provement in glucose tolerance and a decrease in body weight. There was thus a change towards normalization of factors which are characteristi- cally abnormal in endogenous hypertriglycer- idemia, a condition frequently found in association with myocardial infarction in young patients (22). The present work showed that there was an as- sociation between the metabolic normalization and the increase in work performance, but this does not necessarily mean that a less strenuous training program is without effect on the meta- bolic variables. It seems to be of considerable importance to clarify what intensity and dura- tion of work loads and what frequency of working occasions are minimally required to obtain these results.

ACKNOWLEDGEMENTS

Supported by grants from the Swedish Medical Research Council (B72-19X-251-09) and the Swedish National As- sociation against Heart and Chest Diseases.

REFERENCES 1. Bagdade, J. D., Bierman, E. L. & Porte, D., Jr: The

significance of basal insulin levels in the evaluation

Acta tried. scrrrid. 192

of the insulin response to glucose in diabetic and non- diabetic subjects. J. clin. Invest. 46: 1549, 1967.

2. Berchtold, P., Bjorntorp, P., Gustafson, A,, Lindholm, B., Tibblin, G. & Wilhelmsen, L.: Glucose tolerance, plasma insulin and lipids in relation to adipose lis- sue cellularity in men after myocardial infarction. Acta med. scand. 191: 35, 1972.

3. Bjorntorp, P., de Jounge, K., Sjostrom, L. & Sullivan, L.: The effect of physical training on insulin produc- tion in obesity. Metabolism 19: 631, 1970.

4. Bjorntorp, P., Berchtold, P. & Tibblin, G.: Plasma insulin in relation to adipose tissue in men. Diabetes 20:65, 1971.

5. Blix, G., Wretlind, A., Bergstrom, S. & Westin, S. J.: Den svenska folkkostcn. In: VBr Foda, vol. 17, no 7. Statens Institut for Folkhasan, Stockholm.

6. Campbell, D. E.: Influence of several physical activities on serum cholesterol concentrations in young men. J. Lipid Res. 6: 478, 1965.

7. Carlson, L. A.: Determination on serum triglycerides. Acta SOC. Med. upsalien. 64: 208, 1959.

8. Carlson, L. A. & Mossfeldt, F.: Acute effects of prolonged, heavy exercise on the concentration of plasma lipids and lipoproteins in man. Acta physiol. scand. 62: 51, 1964.

9. Cramtr, K. & Isaksson, B.: An evaluation of the Theorell method for the determination of total serum cholesterol. Scand. J. clin. Lab. Invest. 11: 213, 1959.

10. FahlCn, M., Stenberg, J. & Bjorntorp, P.: Insulin secretion in obesity after exercise. Diabetologia. In press 1972.

1. Fitzgerald, P., Hefferman, A. & McFarlane, R.: Serum lipids and physical activity in normal subjects. Clin. Sci. 28: 83, 1965.

2. Froberg, S.: Personal communication, 1970. 3. Goldstein, M. S., Mullick, V., Huddlestun, B. &

Levine, R.: Action of muscular work on transfer of sugars across cell barriers: comparison with action of insulin. Amer. J. Physiol. 173: 212, 1953.

4. Goode, R. C., Firstbrook, J. B. & Shephard, R. J.: Effects of exercise and a cholesterol-free diet on human serum lipids. Canad. J. physiol. Pharmacol. 44: 575, 1966.

5 . Grimby, G., Wilhelmscn, L., Ekstriiin-Jodal, B., Aurell, M., Bjure, J. & Tibblin, G.: Acrobic power and related factors in a population study of men aged 54. Scand. J. clin. Lab. Invest. 26: 287, 1970.

16. Hales, C . N. & Randle, P. J.: Iinmunoassay of insulin with insulin antibody precipitate. Lancet 1: 200, 1963.

17. Holloszy, J. 0.: Biochemical adaptations in muscle. Effects of exercise on mitochondria1 oxygen uptake and respiratory enzyme activity in skeletal muscle. J. biol. Chem. 242: 2278, 1967.

18. Holloszy, J. O., Skinner, J. S., Toro, G. & Curcton, T. K.: Effects of a six month program of endurance exercise on the serum lipids of niddle-aged men. Amer. J . Cardiol. 14: 753, 1964.

19. Keul, J., Doll, E. & Haralambie, G.: Freie Fettsaurcn, Glyzerin und Triglyceride im arteriellen und femoral- venosen Blut vor und nach einem vierwochigen korpcr-

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lichen Training. Pfliigers Arch. ges. Physiol. 316: 194, 1970.

20. Kilbom, A,, Hartley, L. H., Saltin, B., Bjure, J., Grimby, G. & Astrand, I.: Physical training in sedentary middle-aged and older men. I. Medical Evaluation. Scand. J. clin. Lab. Invest. 24: 315, 1969.

21. Levin, K. & Linde, S.: Determination of glucose in blood, cerebrospinal fluid and urine with a new glucose-oxidase reagent. Lakartidningen 59: 3016, 1962.

22. Levy, R. J. & Glueck, C. J.: Hypertriglyceridemia, diabetes mellitus, and coronary vessel disease. Arch. intern. Med. 123: 220, 1969.

23. Lindholm, B.: Body cell mass during long-term cortisone treatment in asthmatic subjects. Acta endo- crin. (Kbh.) 55: 202, 1967.

24. - Body cell mass during long-term treatment with cortisone and anabolic steroids in asthmatic subjects. Acta endocrin. (Kbh.) 55: 222, 1967.

25. Montoye, H. J., van Huss, W. D., Brewer, W. D., Jones, E. M., Ohlson, M. A,, Mahoney, E. & Olson, H.: The effects of exercise on blood cholesterol in middle-aged men. Amer. J. clin. Nutr. 7: 139, 1959.

26. Moore, F. D., Olesen, K. H., McMurray, J. D., Parker, H. V., Ball, M. R. & Boyden, C. M.: The body cell and its supporting environment. Saunders, Philadelphia 1963.

27. Naughton, J. & McCoy, J. F.: Observations on the relationship of physical activity to the serum cho- lesterol concentration of healthy men and cardiac pa- tients. J. chron. Dis. 19: 727, 1966.

28. Mans, L. B., Knittle, J. L. & Hirsch, J.: The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J. clin. Invest. 47: 153, 1968.

29. Siegel, W., Blomqvist, G. & Mitchell, J. H.: Effects of a quantitated physical training program on middle- aged sedentary men. Circulation 41: 19, 1970.

30. Varnauskas, E., Bjorntorp, P., FahlBn, M., Prerovsky, J. & Stenberg, J.: Effects of physical training on exercise. Blood flow and succinic dehydrogenase activity in skeletal muscle. Cardiovasc. Res. 4: 418, 1970.

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