“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 isin-creased.
For the time
being
similar data are scarcely available in children. Ths led us to investigatethe 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
with0.33
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 ofMorgan 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
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) is4.7 ± 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
_
obesepU/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 adults3’912 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 ) inobese
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
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.,
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.,
andRouvier-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.