Blood Glucose, Insulin, and Free Fatty Acid Levels During Oral Glucose Tolerance Tests in 158 Obese Children /. Deschamps, M.D., B. J. Giron, M.D., andH. Lestradet, M.D., Paris, France
SUMMARY
In 158 obese children, aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acid levels were measured during a standard oral glucose tolerance test carried out prior to treatment. The results were analyzed for the total sample as well as for three age groups: 0-5 years, 6-10 years, and 11-15 years and compared with those of 70 normal-weight children matched for age and sex. Glucose tolerance is normal in the obese children. It is different from the controls only two hours after glucose loading, when a slight but significant elevation is found. The glucose levels at one and two hours are significantly higher in the obese children of group III than in the younger ones. Fasting F.F.A. levels are similar in normal and obese children, but the F.F.A. decrease following glucose absorption is significantly diminished in the obese. The F.F.A. levels of the youngest obese are significantly higher than those of the older ones. A constant and important hyperinsulinism, fasting and postabsorptive, is demonstrated in obese children of all ages, even before five years and at the beginning of obesity. Age- and sex-related differences in insulin secretion are much more marked in the obese than in normal children. The degree of hyperinsulinemia is related to the degree of obesity, but not to its duration. The results suggest that hyperinsulinism is associated with obesity from its onset rather than being a long-term consequence of overweight. However, the origin of hyperinsulinism in obesity and the mechanism of insulin resistance still remain obscure. DIABETES 26:89-93, February, 1977.
It has long been recognized that insulin secretion is constantly increased in the obese condition1"3 and that this hyperinsulinism plays a very important role in the maintenance of obesity. Yet it is still questionable From the Group of Research on Diabetes and Nutrition in Children, Hopital Herold, 7, Place Rhin et Danube, 75019 Paris, France. Accepted for publication September 10, 1976. FEBRUARY, 1977
whether it also contributes to its development. Is hyperinsulinemia a secondary phenomenon appearing with and consequent to metabolic, hormonal, and tissue changes due to long-term obesity or is it the symptom of a primary anomaly bearing a direct responsibility in the development of obesity? Certainly young patients, whose obesity is of relatively recent onset and not yet complicated by secondary troubles, are most appropriate for the study of metabolic and hormonal changes in the beginning of obesity. But while there are a great number of investigations in the obese adult, rather few studies have been carried out in obese children, and these, in most cases, have been realized in a small number of subjects. A great variety of interpretations has been advanced, yet the existence of hyperinsulinemia is agreed on by most investigators. 4 " 10 The present study attempted to determine, in a large group of obese children, the importance of hyperinsulinemia in connection with blood sugar and free fatty acid levels and its relation to such other factors as age, sex, and the degree and the duration of obesity. SUBJECTS AND METHODS Before any treatment, 158 obese children, who were not suffering anything other than obesity, were selected for this study. There were 88 boys and 70 girls, and their ages ranged from three months to 15 years (mean age 10.2 years). In 83 children an excessive weight gain had been observed before the age of six, in 58 children between seven and 10 years, and in 17 children after 10 years. The average duration of obesity was 5.6 years, ranging from less than one to 13 years. Their body weight, corrected for height, exceeded by at least 2 standard deviations the mean 89
GLUCOSE, INSULIN, AND FFA LEVELS IN CHILDREN
weight of normal children of the same age. Prior to testing they received a normal diet containing at least 55 to 60 per cent of carbohydrate. During a standard glucose tolerance test (glucose load: 30 gm. per m. 2 of body surface) venous blood samples were taken at 9:00 a.m. at fasting, and 30, 60, 120, and 180 minutes after glucose ingestion for determination of plasma glucose by the Nelson-Somogyi method, 1 1 immunoreactive insulin (I.R.I.) following the radioimmunoassay of Yalow and Berson, 12 and free fatty acids (F.F.A.) by the Duncombe technique. 13 The results were submitted to statistical analysis and compared with those of 70 healthy, normalweight children matched for age and sex. RESULTS The children were divided into three groups according to age: group I: 0-5 years, group II: 6-10 years, group III: 11-15 years. The results are presented in table 1 and figure 1. Very few differences are noted in blood glucose concentrations; however, the increase of blood glucose at one and two hours between groups II and III is significant. The basal and postabsorptive glucose levels of the obese children are very similar to those of normal children except for a slight but significant elevation of the mean blood glucose at two hours in the obese. The fasting F.F.A. levels in the obese children are not different from normal, but the decrease following glucose absorption is diminished significantly in the obese. In the youngest age group of the obese, the F.F.A. levels are significantly higher than in the two older ones. The most striking differences are noticed in plasma insulin concentrations, which are elevated to about twofold normal levels in the obese children, fasting as well as postabsorptive. The analysis of the different o — • 3
group 1 ( 0 - 5
Oral glucose tolerance test in obese children Means ± S.E.M. Time (minutes) 30 0 Normal children n = 70
Blood glucose 81 mg./lOO ml. ±4.0 I.R.I. 8.4* /LtU./ml. ±3.3 F.F.A. 427 ptEq./L. ±14.6
117 ±5.1 50.4* ±6.4 249$ ±11.0
Obese children Blood glucose 83 118 ±3.6 ±5.1 total I.R.I. 16.9* 97.7* n = 158 ±3.6 ±8.5 297$ F.F.A. 405 ±14.6 ±12.6
60 105 ±5.0 43.5* ±5.9 134$ ±7.7 110 ±5.2 76.1* ±7.1 194$ ±11.2
120
86t ±4.7 22.5* ±4.8 95$ ±7.1
97f ±4.5 58.5* ±7.0 167$ ±11.1
180 73 ±4.3 10.4* 63.6 265 ±13.1 75 ±4.5 23.9* ±5.1 266 ±14.8
*, t , and $ significant differences (p
SUMMARY
In 158 obese children, aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acid levels were measured during a standard oral glucose tolerance test carried out prior to treatment. The results were analyzed for the total sample as well as for three age groups: 0-5 years, 6-10 years, and 11-15 years and compared with those of 70 normal-weight children matched for age and sex. Glucose tolerance is normal in the obese children. It is different from the controls only two hours after glucose loading, when a slight but significant elevation is found. The glucose levels at one and two hours are significantly higher in the obese children of group III than in the younger ones. Fasting F.F.A. levels are similar in normal and obese children, but the F.F.A. decrease following glucose absorption is significantly diminished in the obese. The F.F.A. levels of the youngest obese are significantly higher than those of the older ones. A constant and important hyperinsulinism, fasting and postabsorptive, is demonstrated in obese children of all ages, even before five years and at the beginning of obesity. Age- and sex-related differences in insulin secretion are much more marked in the obese than in normal children. The degree of hyperinsulinemia is related to the degree of obesity, but not to its duration. The results suggest that hyperinsulinism is associated with obesity from its onset rather than being a long-term consequence of overweight. However, the origin of hyperinsulinism in obesity and the mechanism of insulin resistance still remain obscure. DIABETES 26:89-93, February, 1977.
It has long been recognized that insulin secretion is constantly increased in the obese condition1"3 and that this hyperinsulinism plays a very important role in the maintenance of obesity. Yet it is still questionable From the Group of Research on Diabetes and Nutrition in Children, Hopital Herold, 7, Place Rhin et Danube, 75019 Paris, France. Accepted for publication September 10, 1976. FEBRUARY, 1977
whether it also contributes to its development. Is hyperinsulinemia a secondary phenomenon appearing with and consequent to metabolic, hormonal, and tissue changes due to long-term obesity or is it the symptom of a primary anomaly bearing a direct responsibility in the development of obesity? Certainly young patients, whose obesity is of relatively recent onset and not yet complicated by secondary troubles, are most appropriate for the study of metabolic and hormonal changes in the beginning of obesity. But while there are a great number of investigations in the obese adult, rather few studies have been carried out in obese children, and these, in most cases, have been realized in a small number of subjects. A great variety of interpretations has been advanced, yet the existence of hyperinsulinemia is agreed on by most investigators. 4 " 10 The present study attempted to determine, in a large group of obese children, the importance of hyperinsulinemia in connection with blood sugar and free fatty acid levels and its relation to such other factors as age, sex, and the degree and the duration of obesity. SUBJECTS AND METHODS Before any treatment, 158 obese children, who were not suffering anything other than obesity, were selected for this study. There were 88 boys and 70 girls, and their ages ranged from three months to 15 years (mean age 10.2 years). In 83 children an excessive weight gain had been observed before the age of six, in 58 children between seven and 10 years, and in 17 children after 10 years. The average duration of obesity was 5.6 years, ranging from less than one to 13 years. Their body weight, corrected for height, exceeded by at least 2 standard deviations the mean 89
GLUCOSE, INSULIN, AND FFA LEVELS IN CHILDREN
weight of normal children of the same age. Prior to testing they received a normal diet containing at least 55 to 60 per cent of carbohydrate. During a standard glucose tolerance test (glucose load: 30 gm. per m. 2 of body surface) venous blood samples were taken at 9:00 a.m. at fasting, and 30, 60, 120, and 180 minutes after glucose ingestion for determination of plasma glucose by the Nelson-Somogyi method, 1 1 immunoreactive insulin (I.R.I.) following the radioimmunoassay of Yalow and Berson, 12 and free fatty acids (F.F.A.) by the Duncombe technique. 13 The results were submitted to statistical analysis and compared with those of 70 healthy, normalweight children matched for age and sex. RESULTS The children were divided into three groups according to age: group I: 0-5 years, group II: 6-10 years, group III: 11-15 years. The results are presented in table 1 and figure 1. Very few differences are noted in blood glucose concentrations; however, the increase of blood glucose at one and two hours between groups II and III is significant. The basal and postabsorptive glucose levels of the obese children are very similar to those of normal children except for a slight but significant elevation of the mean blood glucose at two hours in the obese. The fasting F.F.A. levels in the obese children are not different from normal, but the decrease following glucose absorption is diminished significantly in the obese. In the youngest age group of the obese, the F.F.A. levels are significantly higher than in the two older ones. The most striking differences are noticed in plasma insulin concentrations, which are elevated to about twofold normal levels in the obese children, fasting as well as postabsorptive. The analysis of the different o — • 3
group 1 ( 0 - 5
Oral glucose tolerance test in obese children Means ± S.E.M. Time (minutes) 30 0 Normal children n = 70
Blood glucose 81 mg./lOO ml. ±4.0 I.R.I. 8.4* /LtU./ml. ±3.3 F.F.A. 427 ptEq./L. ±14.6
117 ±5.1 50.4* ±6.4 249$ ±11.0
Obese children Blood glucose 83 118 ±3.6 ±5.1 total I.R.I. 16.9* 97.7* n = 158 ±3.6 ±8.5 297$ F.F.A. 405 ±14.6 ±12.6
60 105 ±5.0 43.5* ±5.9 134$ ±7.7 110 ±5.2 76.1* ±7.1 194$ ±11.2
120
86t ±4.7 22.5* ±4.8 95$ ±7.1
97f ±4.5 58.5* ±7.0 167$ ±11.1
180 73 ±4.3 10.4* 63.6 265 ±13.1 75 ±4.5 23.9* ±5.1 266 ±14.8
*, t , and $ significant differences (p
