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“In Medicine one must pay attention not to plausible theorizing but to experience and reason together. . . . I agree that theorizing is to be approved, provided that it is based on facts, and

systematically makes its deductions from what is observed. . . . But conclusions drawn from

unaided reason can hardly be serviceable; only those drawn from observed fact.” Hippocrates:

Precepts.

. S #{149}

(Short communications of factual material are published here. Comments and criticisms appear as Letters to the Editor.)

-‘

Experience and Reason

Briefly

Recorded

Study

of

the

Glycoregulation

in

the

Obese

Child

During recent years many studies have at-tempted to investigate the degree as well as

the pathophysiologic mechanism of the

meta-bolic and endocrine disorders observed in

obe-sity.

In the adult, the results of these

investiga-tions are rather contradictory. Metabolic stud-ies in obese patients show a variable decrease of the tolerance to carbohydrates4 as well as

of the sensitivity to insulin.2,5 Endocrine data

indicate that the insulin secretion by the pan-creas in response to hyperglycemia3612 or to

hypoglycemiant

sulfonamides2,3,8,bo,1315 is

in-creased.

For the time

being

similar data are scarcely available in children. Ths led us to investigate

the mechanism of the glycoregulation in a

group of obese children and to compare our

re-suits with the findings recorded in the

iitera-hire.

MATERIAL AND METHODS

This study was carried out on a group of 29 children, 17 boys and 12 girls, aged 19i to 15i years. All subjects were free from any endocrine disorder and showed a weight

excess of more than 25% (from 28 to more than 100%) , which has been estimated in

per-cent of the weight corresponding to the height

for the age of the child. Eighteen subjects have no puberal development, whereas 11 subjects show variable degrees of puberty. There was a family history of obesity in 12

patients, and of diabetes in four patients.

Eleven normal children aged 8M2 to 14%

years served as control subjects.

The different tests were performed on suc-cessive days after a fasting of about 12 hours

under normal dietary conditions. For the

hy-perglycemia tests, the patients were given 0.33

gm/kg of glucose intravenously or 3 gm/kg

(with a maximum of 50 gm) of glucose orally;

for the two hypoglycemia tests, they received, intravenously, a maximal dose of insulin of 0.3

U/kg

with

0.33

gm/kg of glucose or 15 mg/kg of tolbutamide.

The blood-sugar level was determined in all

tests

by

the glucose-oxidase micromethod

(Boehringer Biochemica test) . The

immuno-logical insulin was assayed after oral glucose

and intravenous tolbutamide

by

the method of

Morgan and coworkers.16 The plasma free fatty-acid level was determined by the proce-dure of Dole’ during the intravenous glucose

test.

RESULTS

Figure 1 reproduces the blood-sugar curves after oral glucose; the results are expressed

both in absolute values and in absolute

dif-ferences with respect to the initial levels. Fast-ing levels of glucose are not different. It ap-pears that the hyperglycemia is signfficantly greater from 90 to 180 minutes in obese pa-tients when the second mode of expression is used. During this test, the rise of the immuno-logical insulin level occurs later and the mean

values are higher in obese subjects than in con-trol subjects; however, owing to the large dis-persion of the results, the differences are not

significant (Fig. 2).

By plotting the insulin response against the blood-sugar rise for all values of glycemia and insulinemia determined during these tests, it

appears that there is a highly significant

(2)

mg/lOOmL

.

Oral

Glucose

relation 1)0th in the obese subjects (r = 0.55)

and in the control subjects

(

r = 52).

After an intravenous injection of glucose,

the assimilation coefficient (K) is 1.8 ± 0.1%

per minute in the obese subjects and 2.1 ±

0.1% per minute in the control subjects; these

values are not significantly different. Figure 3

represents the variations of the plasma level

of free fatty-acids during this test; in terms

of absolute values, all the results recorded in

ol)ese patients ii the fasting state and during

the glucose load are significantly higher than

those found in control subjects; but, if they

are expressed as a percentage of the fasting

level, the decay is comparable in both groups.

After an intravenous injection of glucose

and of a maximal dose of insulin

simultane-ouslv,

the assimilation coefficient (K max) is

4.7 ± 0.3% per minute in obese subjects and

6.4 ± 0.3% per minute in control subjects;

these values are significantly different (p <

0.05).

Figures 1 and 2 illustrate blood glucose and

insulin (in absolute values) after an

intrave-nous injection of tolbutamide; when expressed

in terms of mean values, the blood-sugar fall is

lesser in obese subjects while the insulin levels are higher. But, owing to their large dispersion, the results are not significantly different from

those recorded in the control subjects.

DISCUSSION

\Vhen the results of the oral glucose tests are

expressed in terms of absolute differences with

respect to the initial blood-sugar level, the

main factor investigated is the effect of the

overload. Under such circumstances, it appears

from our study that obese children show a

definite reduction of their tolerance to glucose administered orally. From the ninetieth minute

following the load up to the end of the test, the

rise of the glycemia is significantly greater in

these subjects than in a control group. At the

end of the test after 180 minutes, the

persis-tence of a significant increase of the

blood-sugar level with respect to the basal value is

i.vToLbutamide

_____1__ I I

10

20

.30

mm

Fic. 1. Clycemia curves expressed in absolute values (upper part) or in absolute differences with respect to the initial level ( lower part ) after oral administration of glucose an(l after intravenous injection of

tolbutamide. Mean values and confidence belts for p ‘( 0.01 (-) and for p < 0.05 (- - -). 0

_

obese

(3)

pU/mi

Oral

Glucose

ixToLbutamide

mm

10

20

mm

.30

F:c. 2. Insulin curves after oral administration of glucose and after intravenous injection of tolbutamide. Mean values and confidence belts for p < 0.05 (- - -) and p < 0.01 (-).

observed in obese subjects. Our findings are in

accordance with those made by Berkowitzl and

Morse and co-workers’ in adults while other

in-vestigators observed a normal tolerance to

glu-cose

after

an oral

load

in both obese adults3’9

12 and children.7’8 In the course of this test, the rise of the insulin level is higher, although not significantly, in our obese subjects as compared

to control subjects, whereas all other studies

mention a significantly greater insulin response

in obese adults3,c,912 as well as in obese

chil-After an intravenous injection of glucose, the

tolerance to carbohydrates in our subjects is

not different from the tolerance shown by the

control subjects; this finding is in accordance

with the data from the literature. ‘‘

Franckson and coworkers2 and MelanP found

a glucose assimilation coefficient

(

K ) in

obese

adults which was significantly lower than in

control subjects; however, the former

investiga-tors show that such a difference can be

evi-denced only when large population samples are

compared.

The free fatty-acids level, as determined

be-fore the injection of glucose, is significantly

higher in obese subjects. This fact is in accor-dance with the observations made 1w most in-vestigators in obese subjects both adultsl,14l21

and children;722 however, Heald and

co-workerslS Persson and Sterkv24 and \Veber and

coworkers15 found no difference between

obese children and control subjects. In the

course of this test, the free fatty-acids decay is

comparable in both groups; this finding is in

accordance with those of Balass&’ and Heald

and won

After a simultaneous intravenous injection of

glucose and of a maximal dose of insulin, the

utilization rate of glucose is significantly

re-duced in our obese subjects. A diminution of

the peripheral action of insulin has also been re-ported by other investigators in obese adults.2,5

The results of the tolbutamide test show that

the fall of the blood sugar and the increase of

the insulin level are not significantly different

in the two groups; our findings concerning the

blood-sugar level are in accordance with

cer-tam data from the literature,5,IO,15 whereas

other investigators report significant differences for the blood-sugar fall’3 as well as for the

in-sulin response.2”’10’113

CONCLUSIONS

In obese children as well as in ol)ese adults,

the kinetics of the glucose utilization are

modified. The present studs’ shows that this

fact is not apparent, neither after an

intrave-nous load of glucose (probably as a result of

(4)

00

12

icxx

p.cent

00

200

C

1600

pEq/L

600

‘C ‘0

0

5

10152025303540

0510152025303540

mm

mm

FIG. 3. Fatty acids curves after intravenous injection of glucose expressed in absolute values ( left ) and

as percentage of the fasting level (right). Mean values and confidence belts for p < 0.01 (-) and

p < 0.05 (---).

small number of subjects observed) nor after

an injection of tolbutamide. But, when the pen-etration of glucose into the cells is forced, ei-ther by the oral administration of a large dose of glucose or by a simultaneous intravenous in-jection of glucose and of a supramaximal dose of insulin, then the metabolic disorder becomes obvious. On the other hand, the insulin level rise is not significantly greater in obese cliii-dern after the oral administration of glucose or an intravenous injection of tolbutamide.

Thus, the inhibition of the penetration of

glucose into the tissues appears to be an early

disturbance in obesity, whereas the hyperactiv-ity of the pancreas, which is observed in obese

adults seems to be a later disorder, secondary

to the modifications of the tissue uptake of glu-cose.

SUMMARY

The glucose kinetics are modified in obese

children. This fact does not appear after an in-travenous load of glucose, but it may be

dis-closed when the penetration of glucose into the

cells is forced either by the oral administration

of a large amount of glucose or by the

simulta-neous intravenous injection of glucose and of a

supramaximal dose of insulin.

The insulin response of the pancreas to oral

glucose and intravenous tolbutamide is not

sig-nificantly increased in obese children.

The rise of the fasting level of free

fatty-acids is significant, but the response of the adi-pose tissue to glucose is comparable to that

ob-served in normal children.

H. LOEB, M.D. Service de P#{233}diatrie H#{244}pitalSt-Pierre H. A. Ooiss, M.D. R. WOLTER, M.D.

N. BRUNET, M.D.

Departments of Pediatrics and Clinical Chemistry

University of Brussels Brussels, Belgium

REFERENCES

1. Berkowitz, D. : Metabolic changes associated

with obesity before and after weight

reduc-tion. J.A.M.A., 187:399, 1964.

2. Franckson, J. R. M., Malaisse, W., Arnould, Y.,

(5)

Bastenie, P. A. : Glucose kinetics in human

obesity. Diabetologia, 2:96, 1966.

3. Kreisberg, R. A., Boshell, B. R., Di Placido, J.,

and Roddam, R. F. : Insulin secretion in obe-sity. New Eng.

J.

Med., 276:314, 1967. 4. Morse, W. I., Sidorov,

J.

J., Soeldner,

J.

S.,

and Dickson, R. C. : Observations on carbo-hydrate metabolism in obesity. Metabolism, 9:666, 1960.

5. Morse, W. I., and Mahabir, R. : Changes in

glucose tolerance and plasma free fatty acids after fasting in obesity. Diabetes, 13:286, 1964.

6. Bagdade, J. D., Bierman, E. L., and Porte, D.: The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects.

J. Clin.

Invest., 48:1549, 1967.

7. Beck, P., Koumans, J. H. T., Winterling, C. A.,

Stein, M. F., Daughaday, W. H., and Kip-nis, D. M. : Studies of insulin and growth

hormone secretion in human obesity. J. Lab.

Clin. Med., 64:654, 1964.

8. Chiumello, G., Del Guercio, M.

J.,

Carnelutti,

M., and Bidone, G. : Etude de la fonction pancr#{233}atique dans l’ob#{233}sit#{233}essentielle de l’enfant. Helv. Paediat. Acta., 23:45, 1968.

9. Karam,

J.

H., Grodsky, G. M., and Forsham, P.

H. : The relationship of obesity and growth

hormone to insulin levels. Ann. N. Y. Acad. Sci., 131:374, 1965.

10. Perley, M., and Kipnis, D. M. : Plasma insulin responses to glucose and tolbutamide in nor-mal weight and obese diabetic and

nondia-betic subjects. Diabetes, 15:867, 1966.

11. Vague, P., Scornavachi,

J.

C.,

and

Rouvier-Le-roy, C. : Variations des acides gras libres plasmatiques apr#{232}s administration orale do

glucose chez les ob#{232}ses. Ann. Endocr. (Paris), 28:787, 1967.

12. Yalow, R. S., Glick, S. M., Roth, J., and Ber-son, S. A. : Plasma insulin and growth hor-mone levels in obesity and diabetes. Ann. N.

Y. Acad. Sci., 131 :356, 1965.

13. Melani, F. : Serum insulin concentration fol-lowing intravenous administration of tolbu-tamide. Acta Diabetologica Latina ( Suppl.

1), 4:106, 1987.

14. Vague, P., Boeuf, G., and Rouvier-Leroy, C.:

The tolbutamide test in obesity. A compara-tive study of blood glucose and plasma

insu-lin. Acta. Diabet. Latina ( Suppl 1), 4:193, 1967.

15. Weber, B., Helge, H., Sihombing, G., and

Werner, E. : Effect of tolbutamide on blood glucose, plasma free fatty acids and insulin in normal and obese children. Israel J. Med.

Sci., 4:290, 1968.

16. Morgan, C. H., Sorensen, R. L., and Lazarow,

A. : Further studies on an inhibition of two

antibody immunoassay systems. Diabetes, 13: 579, 1964.

17. Dole, V. P. : Relation between nonesterified fatty acids in plasma and metabolism of glu-cose.

J.

Clin. Invest., 35:150, 1956.

18. Heald, F. P., Mueller, P.S., and Daugela, M.

z.

: Glucose and free fatty acid metabolism in obese adolescents. Amer.

J.

Clin. Nutrit., 16:256, 1965.

19. Balasse, E. : Role du m#{233}tabolisme glucidique dans la regulation des acides gras libres plasmatiques. Etude dans l’ob#{233}sit#{233},le

din-b#{232}teet le jeimne.

J.

Ann.

Diab#{233}t,Hotel-Dieu, 7:13, 1966.

20. Goldberg, M. and Gordon, E. S. : Energy

me-tabolism in human obesity. Plasma free fatty

acid, glucose and glycerol response to

epi-nephrine. J.A.M.A., 189:616, 1964.

21. Opie, L. H., and Walfish, P. G. : Plasma free

fatty acid concentrations in obesity. New

Eng. J. Med., 268:757, 1963.

22. Becker, A., Spahn, V., and Plenert, W. : Das

Verhalten der freien Fetts#{228}uren fin Serum

bei Kindern unter Noradrenalin. Z. Kinder-heilk., 96:372, 1966.

23. Spahn, U., Plenert, W., and Pathenheimer,

F. : Untersuchungen zur

Fastenbehan-dlung der Adipositas im Kindesalter: II.

Mit-teilung. Die Konzentration der freien

Fetts#{228}uren im Serum bei drastischer

Cab-rieneinschrankung und w#{228}hrenddes absolu-ten Fastens. Z. Kinderheilk, 101:20, 1967. 24. Persson, B. E. H., and Sterky, G. C. G. : Effect

of prolonged fasting and ketogenic diet on

levels of blood lipids and ketones in obese

children. Acta Paediat. Scand., 55:153,

1966.

Life-threatening

Staphylococcal

Disease Following

Ear Piercing

Foreign bodies have long been known to be

important etiobogic sources of pyogenic infec-tions. The frequency with which foreign bod-ies are being inserted into man in our

con-temporary society is unfortunately reinforcing

this principle. Many of these foreign bodies

are of medical origin and are by-products of

improved medical technology. Others, such as the needle of the drug addict,1 reflect the changing modes of our society.

(6)

prac-1970;46;297

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1970;46;297

Pediatrics

H. Loeb, H. A. Ooms, R. Wolter and N. Brunet

Study of the Glycoregulation in the Obese Child

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