Carbohydrate and Lipid Metabolism in Middle-aged,

Physically Well-trained Men

By Per Bjtirntorp, Martin Fahlbn, Gunnar Grimby, Anders Gustafson,

Jan Helm, Per Renstr6m, and Tore Schersten

Body composition, maximal oxygen up- take, plasma lipids, glucose and lipid tolerance, and plasma insulin were examined in middle-aged, physically well-trained men in comparison with randomly selected men of the same age. The well-trained men were char- acterized by a small adipose tissue consisting of small fat cells, and prob- ably by an increased muscle mass. They had an elevated maximal oxygen uptake. Fasting plasma lipids were low. Assimilation of 100 g glucose perorally was very rapid and occurred while insulin concentrations in plasma were much lower than in controls. Fasting plasma insulin values were

also low. Intravenous lipid tolerance test showed a rapid removal rate of triglycerides. Analyses of glucose me- tabolism in vitro in muscle biopsies from these men showed an increased activity in several metabolic pathways. Succinic oxidase activity, as a marker of aerobic capacity as well as gly- cogen contents, was also increased. These results indicate that physical training is a potent factor for regula- tion of plasma insulin levels. It was suggested that qualitative and quanti- tative changes in muscle capacity to metabolize glucose are in some way involved in this regulation.

P HYSICAL TRAINING as well as acute prolonged exercise are known to

cause a decrease in plasma triglyceride concentration.‘-5 The effects on

glucose tolerance and plasma insulin concentration are less frequently studied

in normal individuals. Davidson et aLe have reported a decrease in plasma

insulin concentrations and glucose tolerance after physical training. In the obese patient, physical training lowers plasma insulin even in the absence of

a decrease in body fat. This occurs with unchanged glucose tolerance sug- gesting an influence of training mainly on the insulin sensitivity of the peri-

From the Clinical Metabolic Laborafory of the First Medical Service, Department of Clinical Physiology and Surgical Department II, Saklgren’s Hospifal, Unioersify of Giite- borg, GSfeborg, Sweden.

Received for publication February 25, 1972.

Supported by Grant 872-19x-251-09 from the Swedish Medical Research Council, and by grants from the Swedish National Association Against Heart and Lung Diseases and the Research Council of the Swedish Sports Federation.

Per BjGrntorp, M.D., Ph.D.: Associate Professor of Medicine, First Medical Service, Saklgrenska sjukkuset, University of Gdteborg, Giiteborg, Sweden. Martin FahlCn, M.D.:

First Medical Service, Saklgrenska sjukkuset, University of Gdteborg, Giiteborg, Sweden. Gunnar Grimby, M.D., Ph.D.: Associate Professor of ClinicaI Physiology, Department of Clinical Physiology, Saklgrenska sjukkuset, University of Giiteborg, GBteborg, Sweden. Anders Gustafson, M.D., Ph.D.: Associate Professor of Medicine, First Medical Service, Saklgrenska sjukkuset, University of Giiteborg, GBteborg, Sweden. Jan Holm, M.D.: Surgical Department II, Saklgrenska sjukkuset, University of GBfeborg, Giiteborg, Sweden. Per Renstriim, M.D.: Deparfmenf of Clinical Physiology, Saklgrenska sjukkuset, Uni- versity of Giifeborg, Gafeborg, Sweden. Tore ScherstCn, M.D., Ph.D.: Associnte Professor of Surgery, Surgical Department II, University of Giiteborg, Giiteborg, Sweden.

Metabolism, Vol. 21, No. 11 (November), 1972 1037

1038 BJORNTORP ET AL.

phery.’ Acute work also causes a decrease in insulin secretion in nonobese’

and obese9 subjects. In the present work, a group of middle-aged, physically well-trained men

were examined with glucose tolerance test, plasma insulin and lipids, lipid

tolerance test, and adipose tissue composition, and were compared with

randomly selected men of the same age from the same geographic region. Furthermore, their muscle metabolism was investigated in vitro. The results

showed a high glucose and lipid tolerance, low plasma insulin and lipid

values, and an adipose tissue of limited size containing small fat cells. Muscle

metabolism was characterized by an elevated activity in both aerobic metab-

olism and glycolysis.

MATERIALS AND METHODS

Fifteen well-trained men from 52 to 56 yr were examined. They had been training physically since youth, 2-3 times per wk or more the whole year, and were still active competitors in cross-country running and skiing, belonging to the same group of athletes who have been analyzed physiologically previously. 10 Each training occasion was at least l-hr duration, frequently longer, and consisted of hard exercise in a form of cross-country running (orientering) during the part of the year without snow, and cross-country skiing during winter. Several of them took part in Vasaloppet, a cross-country skiing competition covering a distance of over 80 km.

All gave a history of body weight consistancy over the years (less than 3 kg variation), and their weight was the same as in the compulsory military duty in their early 20s. Body weight was also constant during the months the examinations reported here were per- formed (measured in eight men). None was a vegetarian or kept to any special diets.

The controls for glucose tolerance test with insulin determinations and for plasma lipids and adipose tissue cellularity as well as for maximal oxygen uptake11 consisted of randomly selected men, born 1913,12 and living in the same city as the well-trained men. Controls for the investigation of muscle metabolism were 16 patients, 45-70 yr, operated on for varicose veins. They were not diabetic or obese and received no special diet.13 Controls for the lipid tolerance test were 49 subjects, ages 27-64 yr, who were either apparently healthy or examined for hyperlipidemic conditions.

The men arrived at the laboratory the morning after an overnight fast avoiding physical exercise that morning. A heparinized venous blood sample was taken for determinations of blood glucose14 and plasma insulin ,I5 cholesterol,le and triglycercides.17 They then drank 100 g of glucose dissolved in 200 ml water. Venous blood samples were taken in heparinized tubes for determination of blood glucose and plasma insulin at 30, 60, 90 and 120 min after the ingestion of glucose. The men were sitting in a chair while waiting, and lying down when blood samples were taken,

On another occasion an intravenous lipid tolerance test13 was performed under identical conditions. Six of the men also volunteered for a muscle biopsy on this occasion. This was taken from the vastus lateralis muscle on the middle of the outside of the thigh in four men under local infiltration anesthesia (Carbocain, Bofors, Sweden). In the other two men, care was taken not to infiltrate the region where the biopsy was taken. In the muscle biopsy specimens, of about 500 mg each, glycogen contents19 were determined, as we!! as incorporation of glucose-U-t4C into lipids, glycogen, and carbon dioxide after incubation.13 Succinic oxidase activity20 was also determined.

When the first four muscle biopsies had been performed, it was observed that infiltration anesthesia inhibited the glucose incorporation rate into the measured metabolites. For con- trol glucose incorporation was analyzed before and after infiltration anesthesia in five patients from whom a biopsy was taken in general anesthesia. The mean percentage, inhibi- tions f SEM were found to be 38 X 6%. 45 2 3%, and 52 + 10% for incorporation of glucose label into carbon dioxide, lipid, and glycogen, respectively. Because of the fairly

CARBOHYDRATE AND LIPID METABOLISM 1039

limited variation of this inhibition, it was considered justified to perform a correction of the observed values. Results have been given before and after this correction. In the last two men, biopsy was performed with the local anesthetic agent safely distant from the place of biopsy. Their values were found to be of the same order of magnitude or even higher than the corrected values of the other men, suggesting that the correction was indeed a justifiable procedure.

Percutaneous biopsy of the adipose tissue was taken21 in the gluteal region. The samples obtained were used for determination of fat cell size according to SjGstrGm et al.92 Total body fat was calculated from anthropometric data, and a regression equation12 was ob- tained from a population of randomly selected men of the same age from the same region. Division of total body fat with the average fat cell weight gave an estimate of total fat cell number in the body.

At a third examination, the maximal 02 uptakelo was determined on a bicycle ergometer by a stepwise increase of the work load. Analyses of expiratory gases, collected in a Douglas bag, were performed with a dry gas meter and a micro-Scholander method.

The glucose tolerance tests were performed during the winter of 1970-71. The lipid tolerance tests were performed during the spring of 1971. Plasma lipid determinations were usually determined on more than one occasion throughout the year. The values for one person were averaged. All men were not possible to examine with all metabolic tests. The examinations were performed Z-S days after the latest training session. The metabolic investigations in the 55-yr-old controls were performed during the fall of 1968.

Student’s t test was used for statistical comparisons.

RESULTS

Table I gives individual data for the well-trained men in comparison with the randomly selected controls. It is seen that they had a maximal oxygen uptake that was significantly higher than the controls. Their body weight showed a tendency to be lower than that of the controls.

The body fat mass was significantly smaller. Their adipose tissue was made up of fat cells that were not different in number from those of the controls, but were only half the size of those of the controls.

The glucose tolerance of the well-trained men was higher than the controls, expressing itself as a lower blood glucose value at all points after glucose intake except at 1.20 min, and also a lower sum of glucose values during glucose tolerance test. The fasting and the 120-min blood glucose values were actually higher in the well-trained men, although only the former were sig- nificant. In the well-trained men blood glucose concentration after the inges- tion of glucose was raised above fasting glucose only in the 30-min value (p<O.OOl). This is in contrast to the controls where hyperglycemia persisted for a longer time, giving blood glucose values above the fasting concentration (p<O.OOl) at 30, 60, and 90 min.

The insulin values were markedly lower at all points including the sum of insulin values during the glucose tolerance test. Plasma triglycerides and cholesterol were also lower in the well-trained men in comparison with controls.

The intravenous lipid tolerance test showed a high removal rate in the well- trained men. In comparison with a mixed material of controls they did not, however, apparently differ from the removal rate expected at their low tri- glyceride values (Fig. 1).

Figure 2 shows the results of determinations in muscle biopsies in relation

1040 BJORNTORP ET AL.

Table 1. Metabolic, Body Composition, and Oxygen Consumption Data

Max.

Fat Fat oxygen Trigly- Body Body ccl I cell uptake ceride

Age weight fat weight number (liters/ (mg/lOO Cholesterol Subject (yr) (kg) (kg) (wg) ( x 10’0) min) ml) (mg/lOO ml)

O.D. 56 61 6 0.47 1.3 2.6 61 187 J.I. 52 71 13 0.37 3.5 2.8 91 164 M.O. 54 64 12 0.32 3.7 3.0 47 187 H.A. 55 67 8 0.30 2.7 3.4 63 229 I.A. 52 72 13 0.51 2.8 2.6 74 197 R.J. 54 64 5 0.08 6.3 3.1 51 173 A.L. 56 82 10 0.27 3.7 2.7 98 171 G.S. 53 65 11 0.56 2.9 2.0 61 218 E.B. 53 84 20 0.75 2.7 2.3 120 206 A.A. 55 84 20 0.28 7.2 2.9 97 250 P.E. 55 67 6 0.21 2.8 3.1 69 248 P.C. 52 72 10 0.11 9.1 2.6 78 159 A.C. 55 78 0 0.12 0 3.0 - - O.C. 53 61 5 0.28 1.8 2.5 146 234 A.W. 56 73 8 0.10 6.0 - 62 220 Mean-ISEM 54kO.4 7lf2 lo+1 0.3220.05 3.820.6 2.8?0.10 8027 203k8 Controls 55 7522 16+1 0.83kO.04 2.8kO.l 2.3~0.05*109~7 25725

(meankSEM) 06 45)

l N, 539. - NS <O.OOl <O.OOl NS <O.OOl <O.Ol <O.OOl

to the values of the controls. Succinic oxidase activity (34 2 2 ml 0%/g protein

X h-l, means * SEM) was considerably higher than in controls (p<O.OOl)

and muscle contents of glycogen (29 + 5 mg/g) was also elevated (p<O.OOl).

Incorporation rate of glucose level into glycogen (~<o.ooI), livid (~<o.ooI),

and carbon dioxide (~<o.ooI) was also significantly increased in comparison with controls.

DISCUSSION

The well-trained men were leaner than the controls. However, the body weight showed only a tendency to be lower. This is probably due to an in- crease in the muscle mass of these subjects. An elevation of muscle mass and and small adipose tissue, made up of small fat cells, thus probably charac- terized the body composition of these men in relation to their controls of mainly sedentary men.

The well-trained men could assimilate IOO g of glucose with an increase in blood glucose concentration only during the first half-hour after ingestion. This fast glucose assimilation occurred with very little insulin increase in plasma. As a matter of fact, the sum of insulin values of these men is very close to that of men with maturitv-onset diabetes mellitus during the same gluose tolerance test (114 PH). 23 This means a remarkably high insulin sensi- tivity in the peripheral tissues of the well-trained men. ‘When calculated as

CARBOHYDRATEANDLlPlDMETABOLlSM 1041

for Well-trained Middle-aged Athletes in Comparison With Controls

0’ Insulin (&/ml) Glucose (mg/lOO ml)

30’ 60’ 90’ 120’ Sum 0’ 30’ 60’ 90’ 120’ Sum

<2 36 14 17 10 77 69 -----_ - ----__

<2 42 10 8 11 71 -_----

<2 49 25 8 2 84 <2 8 49 16 32 105 <2 19 12 14 16 61 4 76 128 102 75 385

<2 7 21 23 6 58 0 28 56 32 27 143

----__

<2 34 6 4 9 53 <2 25 18 15 22 80 ----__

<2_Cl 32a6 34&1224+9 21f7 112231 10+-l 7926 95&9 96212 55+6 337+29

- - 71 82 - -

77 146 71 97 74 115 69 127 71 94 73 104 -

74 78 -

7321 6421

97 -

-- --

63 57 65 338 -- - _

77 64 47 411 108 93 98 465 81 84 81 435 90 71 69 426 92 69 61 387 91 48 69 385

- ----

117 52 58 91 392 90 76 77 97 418 - - - - -

10746 7925 69-+-4 75k5 403all 12123 108-c5 8624 6923 498k14

62 69 72 369 -- --

< < < < < < < < < < NS < 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.05 0.001 0.01 0.01

insulin/glucose concentrations, ratios of 0.28 and 0.76 are obtained in the

sum of insulin and glucose values for the well-trained men and the controls, respectively.

It was recently described that when obese patients are physically trained, plasma insulin concentrations are lower, and there is probably an increased insulin sensitivity of the peripheral tissues. ’ It is noteworthy, however, that the ins&n vahres obtained after training in these patients, although within the range of mainly sedentary controls, are still considerably higher than those found in the present material of trained, nonobese subjects. Whether the remaining difference in the obese patients both in terms of insulin production and insulin/glucose values is due to a less intensive training of shorter dura- tion than in the present trained nonobese subjects, or due to a remaining hyperactive insulin-producing apparatus in the obese, or due to other factors cannot be decided.

Succinic oxidase, as a marker of mitrochondrial activity in muscle, was in- creased. This was also the case with glycogen contents and synthesis in vitro, as well as glucose oxidation and lipid synthesis from glucose in muscle. Short et a1.24,25 have recently also demonstrated an increase not only of aerobic enzymes but also of glycogen synthesis and breakdown after physical training. This is in agreement with findings in muscle relatively rich in mitochondria26 where also hexokinase activity has been found to be elevated.27*28 It seems

1042 BJORNTORP ET AL.

500 - 0

400.

‘i 2 0

T 0 300.

F 0 0

0 0 c_

240.

0

i o”o 0 0 0 m p‘

00 0

Fig. 1. Rate of removal o

ocz 0” 100. 0 9. o*oOoo

0 (kz) of an i.v. adminis- 9 0 :‘p, 08 % o ’ tered triglyceride emul- o

0 sion in controls (open circles), and in physically

50 100 well-trained, middle-aged K2lpcr ccnt/mtnj men (solid circles).

60- 600

.

.

T 711

50- .

500

LO’ 400

30.

zo-

10.

O-

. 300

.

. . . ! 200

100

SUCCI N/C 0

GLYCOGEN

I OXIDASE

GLYCOGEN

-I.+

LIPID

-Itic

(X0.1)

Fig. 2. Contents of glycogen (mg/g), activity of succinic oxidase (ml 02/g

800

700

.

protein X h-l) and rate of incorporation of U-14C-gIucose into glycogen, lipids and carbon dioxide (nmole glucose/g X h-l) in the vastus lateralis muscle of physically well-trained, middle-aged men in comparison with controls. Control values are given as means * 2 SD. Incorporation data given before (open circles) and after (solid circles) correction for inhibition of activities by infiltra- tion anesthesia (see Materials and Methods).

CARBOHYDRATE AND LIPID METABOLISM 1043

reasonable that the findings in vitro is an indication of an increased glucose assimilation potential in vivo, and that the changes of muscle uptake of glucose after training are at least one important means whereby the glucose tolerance of these subjects is so high.

The previously described association between a low degree of filling of

adipose tissue and low plasma insulin va1ues12,2g,30B31 is thus also found in

the present work. It is doubtful whether the insulin responsiveness of adipose

tissue as such is related to this correlation as discussed before.32 It seems more likely that the plasma insulin concentration is dependent on insulin responsive-

ness of other tissues than adipose tissue, such as muscle. The present results

in well-trained men with a probable increased mass of metabolically active

muscles, support the hypothesis that quantitative and qualitative factors in

muscle play an important role for the insulin sensitivity of the whole organism, and thus the production of insulin.

ACKNOWLEDGMENT

We are grateful to the well-trained men who willingly and enthusiastically volunteered in these several time-consuming and uncomfortable investigations. The skillful secretarial and technical assistance of Inga Hvass, Majvor Karlsson, Agneta Eggers, Monica Hadders, Marita Hedberg, Gunilla Brodin-Persson, Agneta Orrhult, and Gunilla Pacsay is gratefully acknowledged.

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