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Carbohydrate metabolism in children: (1) Blood sugar, serum insulin, and growth hormone during oral glucose tolerance tests; (2) Blood sugar during the cortisone glucose tolerance test
Carbohydrate Metabolism in Children :
(1) Blood Sugar, Serum Insulin, and Growth Hormone During Oral Glucose Tolerance Tests; (2) Blood Su gar D uring the Cortisone Glucose Tolerance Test By Harold Oral glucose tolerance tests have been performed on 159 children 1 wk to 12 yr of age, using capillary specimens. Mean glucose responses varied only between the 1’/2-3-yr age group and the 3-12-yr group at 60 mm postglucose ingestion. There were no agerelated differences in insulin and growth hormone responses. Cortisone glucose tolerance tests have been
S. Cole carried out with 113 normal children without a family history of diabetes, and the data analyzed by age group (1’/2 yr-<4 yr, 4-<8 yr, 8-12 yr). The responses of the youngest group differed significantly from those of children older than 4 yr. There were no significant sex differences. The responses of the children 4-12 yr of age provide standards for this test.
M
UCH PRESENT DAY RESEARCH is focused on the early identification of children with diabetes mellitus before the onset of clinical symptoms.’ This might provide time for the institution of preventive therapy.2.3 The most widely used test for the definitive diagnosis of diabetes is the oral glucose tolerance test (OGTT). However, the cortisone glucose tolerance test (CGTT), although primarily a research tool, has been utilized with increased frequency as an approach to the earlier detection of diabetes. Previous standards for evaluating the OGTT and the CGTT have been derived from studies performed on adult subjects. This study was undertaken to establish capillary blood sugar values in children during both the OGTT and the CGTT, and also serum insulin and growth hormone values during the OGTT. MATERIALS
AND METHODS
OGTT and Serum Insulin and Growth Hormone Determinations Three-hr capillary blood OGTTs were performed on a total of 159 children in three age groups; 1 wk-1Yz yr, 11/z-3 yr, and 3-12 yr. All children were ambulatory and in good health and had negative family histories for diabetes. The distribution of subjects used in this study according to age, sex, and race is shown in Table 1. The required specimens of blood were obtained with the Unopette (Fig. I). This is a microtechnique and requires only 0.02 ml of blood. Blood sugar values were From the Department of Pediatrics and the Diabetes Center, New York Medical College, Flower and Fifth Avenue Hospitals, and Metropolitan Hospital, New York, N. Y. Presented at the Conference on Chemical Diabetes Mellitus in Childhood, Ponte Vedra Beach, Florida, December 5-6, 1970. Received for publication April 1972. Harold S. Cole, M.D.: Associate Professor of Pediatrics, New York Medical College, New York, N. Y. Mefabolism,
Vol. 22, No. 2 (February),
1973
289
290
HAROLD
S. COLE
Fig. 1. The Unopette, showing the plastic reservoir containing sodium fluoride and a self-filling pipette.
Table 1. Distribution of Subjects Used in this Study of OGTT, According to Age, Sex, and Race* Puerto Ages
Males
O-18 mo 1 r/2-3 yr 3-12 yr
8 14 50 72
Total
White----
Black
Rican Females
a 7 42 57
Males
Females
6 1 5 12
3 3 10 16
Males
Females
Total
25 25 109 159
2 2
‘No infants less than 1 wk of age are included.
Table 2. Distribution of Subjects Used in this Study of CGTT According to Age, Sex, and Race ._-. Puerto Ages
Males
l-<4 yr 4-<8 yr 8-f2 yr Total
Rican Females
17 14 13 44
Table 3. The Mean t
Fasting
30 min
Black Males
7 24 23 54
3 3
White
Females
1 2 2 5
Males
Females
1 1 2 4
Total
26 43 44 113
2 1 3
2 SD Values of Capillary Blood Sugar in mg/lOO ml for All Age Groups Combined 60 min
90 min
120 min
180 min --
71.8 $ 16.4
118.6 f
41.6
107.8 2 41.4
100.6 * 32.4
94.1 c 25.2
75.3 % 29.6
(112)’ 9.6 f 0.65
15 min
Boys and Girls l’/z-12
of subjects
(110)’ 16.9 21.12
Growth
(112) 11.6 rt 0.76
tested given in parentheses.
yr
15 min
of Serum
During
combined
(110) 24.9 2 2.03
90 min
are shown
‘Number
of subjects
Mean Value k SEM 1 SD 2SD Range 3rd percentile range 97th percentile range
tested given in parentheses.
84.2 2 1.60 I? 14.9 54.4114.0 56.2112.2
Fasting (67)’
149.5 2 2.90 ?I 26.7 96.1202.9 99.3199.7
30 min (65)
138.5 k 3.44 k 31.9 74.7202.3 78.5198.5
60 min (66)
in Table 3.
(115) 21.0 -e 1.67
120 min
(109) 9.6 k 0.66
90 min
120.9 ?I 2.61 & 24.2 72.5169.3 75.4166.4
90 min (66)
(105) 11.9 I!I 0.76
180 min
(105) 17.0 c 1.86
160 min
111.6 -c 2.47 + 22.9 65.8 157.4 68% 154.7
120 min (66)
86.0 t 1.96 2 18.2 49.6122.4 51.8120.2
160 min (66)
4-8 and 8-12 yr combined,
(114) 10.2 r+ 0.85
120 min
for All Ages and Sexes Combined
(114) 10.2 f 0.79
60 min
the OCTT
and girls in all age groups
(113) 10.9 -t- 0.94
30 min
Hormone
for boys
(115) 32.5 e 2.15
60 min
the OGTT for All Ages and Sexes Combined
Table 6. Values in mg/lOO ml of Capillary Blood Sugar During the CGTT for Boys and Girls in the Two Age Groups 1 SD, 2 SD Range, and the 3rd and 97th Percentiles for Each of the Testing Periods
*Number
Mean Value k SEM
in mpg/ml
Fasting
Table 5. Values
hormone
30 min
During
(112) 29.3 ?I 2.34
of Serum Insulin
(113) 19.6 21.29
in pU/ml
‘Number of subjects tested given in parentheses. TThe values for the mean -t SEM for serum growth
Boys and Girls 1’/2-12 yr Mean Valuest k SEM
Fasting
Table 4. Values
292
HAROLD
S. COLE
determined with the AutoAnalyzer following the methodology of Gray, Stowe, and Holden. Oral glucose solution was administered according to age and weight. Subjects aged 1 wk-1% yr received glucose in the amount of 2.5 g/kg body weight; those aged 1%-3 yr received 2.0 g/kg body weight; and those aged 3-12 yr received 1.75 g/kg body weight. Insulin and growth hormone (GH) levels were determined during the OGTT on 125 of the subjects over 1% yr of age. Immunoreactive serum insulin and GH were determined simultaneously by a modification of the Morgan technique.6,’
Cortisone Glucose Tolerance
Testing
Three-hour CGTTs were performed on a total of 113 children in three age groups; lx/z-<4 yr, 4 yr-<8 yr, and 8-12 yr of age. These children were also ambulatory and in good health and had negative family histories for diabetes. They had all been examined 1-2 wk previously by OGTTs, the results of which conformed to the previously established standards for normal children. The distribution of subjects used in this study is shown in Table 2. The capillary blood microtechnique was used with the AutoAnalyzer and oral glucose was administered according to age and weight as described above. The total cortisone dosage was 280 mg/ M2 given in two equally divided doses 8% and 2 hr before testing.*
RESULTS
Blood Sugar,
Serum
Insulin, and GH During the OGTT
The mean blood sugar values of each of the three age groups were compared with one another for each of the sampling periods, and also with the overall mean for each period. The only significant difference in the means was between the 11/z-3-yr age group and the 3-12 yr age group at the 60-min testing period. Overall means and the values of *2 SD and the 3rd97th percentiles were determined for the three age groups combined. Values for the 22 SD are shown in Table 3. No significant differences were found either for insulin or growth hormone at any of the testing periods between all age groups or between the sexes. The values for the mean 2 SEM for serum insulin and GH for boys and girls in all age groups combined are shown in Tables 4 and 5, respectively. Blood Sugar
Values
During
the CGTT
Ninety-six tests for significance were performed in attempting to compare the children with respect to age and sex. These tests apparently isolated the 11/z to less than 4-yr age group from the others, possibly due to the relatively small size of this group, which contained only 18 males and 8 females. The values for boys plus girls in the other two age groups combined (4-12 yr) could be used for children of these ages. The values for the *2 SD range for boys and girls from 4 to 12 yr of age were: fasting, 54.4-114.0; 30 min, 96.1-202.9 mg/lOO ml; 60 min, 74.7-202.3; 90 min, 72.5-169.3; 120 min, 65.8-157.4; and 180 min, 49.6122.4 mg/lOO ml. These values, along with the mean and the 3rd and 97th percentiles, are shown in Table 6.
CARBOHYDRATE
METABOLISM
IN CHILDREN
293
DISCUSSION
Epidemiologic studies of diabetes have been increasing in number throughout the world. The importance of identifying children predisposed to this disease and evaluating the effectiveness of early therapy is obvious.2,3 Standardization of the oral glucose tolerance test in children has become essential. In the studies described in this paper, standard values for blood sugar serum insulin, and GH in children during the OGTT have been obtained. Mean glucose responses varied only between the 11/z-3 yr age group and the 3-12 yr group at 60 min postglucose administration. There were no age-related differences in insulin and GH responses. The CGTT does offer promise in the search for earlier detection of diabetes, although it must still be considered primarily a research tool.g It was considered essential to use a cortisone dosage primarily adapted for children. In the present study, the recommendations of Wajchenberg et al. were followed, using a total dose of 280 mg/M2 of cortisone acetate.* The higher values of blood sugar observed during the CGTT were probably due to increased gluconeogenesis. Decreased utilization of glucose and decreased sensitivity to endogenous insulin must also be considered. It is hoped that the data obtained in this study might be of help in identifying those children who are potential diabetics, and thus provide time for the institution of prophylactic therapy when it becomes available. REFERENCES 1. Camerini-Davalos, R. A., Caulfield, J. B., Rees, S. B., Lozano-Casteneda, O., Naldjiian, S., and Marble A.: Preliminary observations in subjects with prediabetes. Diabetes 12:508, 1963. 2. Jackson, R.: Insulin treatment of children with late stage of chemical diabetes. In Camerini-Davalos, R. A., and Cole, H. S. (Eds.): Early Diabetes. New York, Academic, 1970, p. 401. 3. Fajans, S. S., Floyd, J. C., Conn, J. W., and Pek, S.: The course of asymptomatic diabetes of children, adolescents and young adults. In Camerini-Davalos, R. A., and Cole, H. S. (Eds.): Early Diabetes. New York, Academic, 1970, p. 377. 4. Gray, D. H., Stowe, N. W., and Holden, R. A.: Rapid automated micro screening for diabetes. HSMHA Health Rep. 79:1081, 1964. 5. Hoffman,
W. S.: A rapid photoelectric
method for determination of glucose in blood urine. J. Biol. Chem. 120:51, 1937. 6. Morgan, C. R.: Immunoassay of human insulin and growth hormone simultaneously using 1311 and 1251 tracers. Proc. Sot. Exp. Biol. Med. 123~230, 1966. 7. Opperman, W., Mehtalia, S. D., Sodero, E. C., Cole, H. S., and Camerini-Davalos, R. A.: A sensitive micromethod for the simultaneous determination of insulin and growth hormone by double antibody precipitation. Clin. Biochem. 2:341, 1969. 8. Wajchenberg, B. L., Pupo, A. A., Quintao, E. R., Leon, N., and Saldanha, I’. H.: Predisposition to diabetes as evaluated by the cortisone-glucose tolerance test in children. Diabetes 13:569, 1964. 9. Fajans, S. S., and Conn, J. W.: Comments on the cortisone-glucose tolerance test. Diabetes 10:63-67, 1961.
(1) Blood Sugar, Serum Insulin, and Growth Hormone During Oral Glucose Tolerance Tests; (2) Blood Su gar D uring the Cortisone Glucose Tolerance Test By Harold Oral glucose tolerance tests have been performed on 159 children 1 wk to 12 yr of age, using capillary specimens. Mean glucose responses varied only between the 1’/2-3-yr age group and the 3-12-yr group at 60 mm postglucose ingestion. There were no agerelated differences in insulin and growth hormone responses. Cortisone glucose tolerance tests have been
S. Cole carried out with 113 normal children without a family history of diabetes, and the data analyzed by age group (1’/2 yr-<4 yr, 4-<8 yr, 8-12 yr). The responses of the youngest group differed significantly from those of children older than 4 yr. There were no significant sex differences. The responses of the children 4-12 yr of age provide standards for this test.
M
UCH PRESENT DAY RESEARCH is focused on the early identification of children with diabetes mellitus before the onset of clinical symptoms.’ This might provide time for the institution of preventive therapy.2.3 The most widely used test for the definitive diagnosis of diabetes is the oral glucose tolerance test (OGTT). However, the cortisone glucose tolerance test (CGTT), although primarily a research tool, has been utilized with increased frequency as an approach to the earlier detection of diabetes. Previous standards for evaluating the OGTT and the CGTT have been derived from studies performed on adult subjects. This study was undertaken to establish capillary blood sugar values in children during both the OGTT and the CGTT, and also serum insulin and growth hormone values during the OGTT. MATERIALS
AND METHODS
OGTT and Serum Insulin and Growth Hormone Determinations Three-hr capillary blood OGTTs were performed on a total of 159 children in three age groups; 1 wk-1Yz yr, 11/z-3 yr, and 3-12 yr. All children were ambulatory and in good health and had negative family histories for diabetes. The distribution of subjects used in this study according to age, sex, and race is shown in Table 1. The required specimens of blood were obtained with the Unopette (Fig. I). This is a microtechnique and requires only 0.02 ml of blood. Blood sugar values were From the Department of Pediatrics and the Diabetes Center, New York Medical College, Flower and Fifth Avenue Hospitals, and Metropolitan Hospital, New York, N. Y. Presented at the Conference on Chemical Diabetes Mellitus in Childhood, Ponte Vedra Beach, Florida, December 5-6, 1970. Received for publication April 1972. Harold S. Cole, M.D.: Associate Professor of Pediatrics, New York Medical College, New York, N. Y. Mefabolism,
Vol. 22, No. 2 (February),
1973
289
290
HAROLD
S. COLE
Fig. 1. The Unopette, showing the plastic reservoir containing sodium fluoride and a self-filling pipette.
Table 1. Distribution of Subjects Used in this Study of OGTT, According to Age, Sex, and Race* Puerto Ages
Males
O-18 mo 1 r/2-3 yr 3-12 yr
8 14 50 72
Total
White----
Black
Rican Females
a 7 42 57
Males
Females
6 1 5 12
3 3 10 16
Males
Females
Total
25 25 109 159
2 2
‘No infants less than 1 wk of age are included.
Table 2. Distribution of Subjects Used in this Study of CGTT According to Age, Sex, and Race ._-. Puerto Ages
Males
l-<4 yr 4-<8 yr 8-f2 yr Total
Rican Females
17 14 13 44
Table 3. The Mean t
Fasting
30 min
Black Males
7 24 23 54
3 3
White
Females
1 2 2 5
Males
Females
1 1 2 4
Total
26 43 44 113
2 1 3
2 SD Values of Capillary Blood Sugar in mg/lOO ml for All Age Groups Combined 60 min
90 min
120 min
180 min --
71.8 $ 16.4
118.6 f
41.6
107.8 2 41.4
100.6 * 32.4
94.1 c 25.2
75.3 % 29.6
(112)’ 9.6 f 0.65
15 min
Boys and Girls l’/z-12
of subjects
(110)’ 16.9 21.12
Growth
(112) 11.6 rt 0.76
tested given in parentheses.
yr
15 min
of Serum
During
combined
(110) 24.9 2 2.03
90 min
are shown
‘Number
of subjects
Mean Value k SEM 1 SD 2SD Range 3rd percentile range 97th percentile range
tested given in parentheses.
84.2 2 1.60 I? 14.9 54.4114.0 56.2112.2
Fasting (67)’
149.5 2 2.90 ?I 26.7 96.1202.9 99.3199.7
30 min (65)
138.5 k 3.44 k 31.9 74.7202.3 78.5198.5
60 min (66)
in Table 3.
(115) 21.0 -e 1.67
120 min
(109) 9.6 k 0.66
90 min
120.9 ?I 2.61 & 24.2 72.5169.3 75.4166.4
90 min (66)
(105) 11.9 I!I 0.76
180 min
(105) 17.0 c 1.86
160 min
111.6 -c 2.47 + 22.9 65.8 157.4 68% 154.7
120 min (66)
86.0 t 1.96 2 18.2 49.6122.4 51.8120.2
160 min (66)
4-8 and 8-12 yr combined,
(114) 10.2 r+ 0.85
120 min
for All Ages and Sexes Combined
(114) 10.2 f 0.79
60 min
the OCTT
and girls in all age groups
(113) 10.9 -t- 0.94
30 min
Hormone
for boys
(115) 32.5 e 2.15
60 min
the OGTT for All Ages and Sexes Combined
Table 6. Values in mg/lOO ml of Capillary Blood Sugar During the CGTT for Boys and Girls in the Two Age Groups 1 SD, 2 SD Range, and the 3rd and 97th Percentiles for Each of the Testing Periods
*Number
Mean Value k SEM
in mpg/ml
Fasting
Table 5. Values
hormone
30 min
During
(112) 29.3 ?I 2.34
of Serum Insulin
(113) 19.6 21.29
in pU/ml
‘Number of subjects tested given in parentheses. TThe values for the mean -t SEM for serum growth
Boys and Girls 1’/2-12 yr Mean Valuest k SEM
Fasting
Table 4. Values
292
HAROLD
S. COLE
determined with the AutoAnalyzer following the methodology of Gray, Stowe, and Holden. Oral glucose solution was administered according to age and weight. Subjects aged 1 wk-1% yr received glucose in the amount of 2.5 g/kg body weight; those aged 1%-3 yr received 2.0 g/kg body weight; and those aged 3-12 yr received 1.75 g/kg body weight. Insulin and growth hormone (GH) levels were determined during the OGTT on 125 of the subjects over 1% yr of age. Immunoreactive serum insulin and GH were determined simultaneously by a modification of the Morgan technique.6,’
Cortisone Glucose Tolerance
Testing
Three-hour CGTTs were performed on a total of 113 children in three age groups; lx/z-<4 yr, 4 yr-<8 yr, and 8-12 yr of age. These children were also ambulatory and in good health and had negative family histories for diabetes. They had all been examined 1-2 wk previously by OGTTs, the results of which conformed to the previously established standards for normal children. The distribution of subjects used in this study is shown in Table 2. The capillary blood microtechnique was used with the AutoAnalyzer and oral glucose was administered according to age and weight as described above. The total cortisone dosage was 280 mg/ M2 given in two equally divided doses 8% and 2 hr before testing.*
RESULTS
Blood Sugar,
Serum
Insulin, and GH During the OGTT
The mean blood sugar values of each of the three age groups were compared with one another for each of the sampling periods, and also with the overall mean for each period. The only significant difference in the means was between the 11/z-3-yr age group and the 3-12 yr age group at the 60-min testing period. Overall means and the values of *2 SD and the 3rd97th percentiles were determined for the three age groups combined. Values for the 22 SD are shown in Table 3. No significant differences were found either for insulin or growth hormone at any of the testing periods between all age groups or between the sexes. The values for the mean 2 SEM for serum insulin and GH for boys and girls in all age groups combined are shown in Tables 4 and 5, respectively. Blood Sugar
Values
During
the CGTT
Ninety-six tests for significance were performed in attempting to compare the children with respect to age and sex. These tests apparently isolated the 11/z to less than 4-yr age group from the others, possibly due to the relatively small size of this group, which contained only 18 males and 8 females. The values for boys plus girls in the other two age groups combined (4-12 yr) could be used for children of these ages. The values for the *2 SD range for boys and girls from 4 to 12 yr of age were: fasting, 54.4-114.0; 30 min, 96.1-202.9 mg/lOO ml; 60 min, 74.7-202.3; 90 min, 72.5-169.3; 120 min, 65.8-157.4; and 180 min, 49.6122.4 mg/lOO ml. These values, along with the mean and the 3rd and 97th percentiles, are shown in Table 6.
CARBOHYDRATE
METABOLISM
IN CHILDREN
293
DISCUSSION
Epidemiologic studies of diabetes have been increasing in number throughout the world. The importance of identifying children predisposed to this disease and evaluating the effectiveness of early therapy is obvious.2,3 Standardization of the oral glucose tolerance test in children has become essential. In the studies described in this paper, standard values for blood sugar serum insulin, and GH in children during the OGTT have been obtained. Mean glucose responses varied only between the 11/z-3 yr age group and the 3-12 yr group at 60 min postglucose administration. There were no age-related differences in insulin and GH responses. The CGTT does offer promise in the search for earlier detection of diabetes, although it must still be considered primarily a research tool.g It was considered essential to use a cortisone dosage primarily adapted for children. In the present study, the recommendations of Wajchenberg et al. were followed, using a total dose of 280 mg/M2 of cortisone acetate.* The higher values of blood sugar observed during the CGTT were probably due to increased gluconeogenesis. Decreased utilization of glucose and decreased sensitivity to endogenous insulin must also be considered. It is hoped that the data obtained in this study might be of help in identifying those children who are potential diabetics, and thus provide time for the institution of prophylactic therapy when it becomes available. REFERENCES 1. Camerini-Davalos, R. A., Caulfield, J. B., Rees, S. B., Lozano-Casteneda, O., Naldjiian, S., and Marble A.: Preliminary observations in subjects with prediabetes. Diabetes 12:508, 1963. 2. Jackson, R.: Insulin treatment of children with late stage of chemical diabetes. In Camerini-Davalos, R. A., and Cole, H. S. (Eds.): Early Diabetes. New York, Academic, 1970, p. 401. 3. Fajans, S. S., Floyd, J. C., Conn, J. W., and Pek, S.: The course of asymptomatic diabetes of children, adolescents and young adults. In Camerini-Davalos, R. A., and Cole, H. S. (Eds.): Early Diabetes. New York, Academic, 1970, p. 377. 4. Gray, D. H., Stowe, N. W., and Holden, R. A.: Rapid automated micro screening for diabetes. HSMHA Health Rep. 79:1081, 1964. 5. Hoffman,
W. S.: A rapid photoelectric
method for determination of glucose in blood urine. J. Biol. Chem. 120:51, 1937. 6. Morgan, C. R.: Immunoassay of human insulin and growth hormone simultaneously using 1311 and 1251 tracers. Proc. Sot. Exp. Biol. Med. 123~230, 1966. 7. Opperman, W., Mehtalia, S. D., Sodero, E. C., Cole, H. S., and Camerini-Davalos, R. A.: A sensitive micromethod for the simultaneous determination of insulin and growth hormone by double antibody precipitation. Clin. Biochem. 2:341, 1969. 8. Wajchenberg, B. L., Pupo, A. A., Quintao, E. R., Leon, N., and Saldanha, I’. H.: Predisposition to diabetes as evaluated by the cortisone-glucose tolerance test in children. Diabetes 13:569, 1964. 9. Fajans, S. S., and Conn, J. W.: Comments on the cortisone-glucose tolerance test. Diabetes 10:63-67, 1961.