Obesity and the Metabolic Syndrome in Children and Adolescents
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Weiss et al. (June 3 issue)1 report the prevalence of the metabolic syndrome in children and adolescents on the basis of their findings with the use of specific markers. Hepatic manifestations of the metabolic syndrome include nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.2,3 A valuable biomarker for both of these disorders is an elevated alanine aminotransferase level.4 We conducted a study involving 37 overweight children (body-mass index z score, 1.5 to 2.0) and 145 obese children (BMI z score, greater than 2.0) who were otherwise healthy to investigate the prevalence of elevated levels of liver enzymes; the mean age of the children was 9 years (range, 1 to 12). We found a significantly elevated mean level of alanine aminotransferase, which increased as the BMI z score increased (Figure 1). In 48 percent of the patients, the alanine aminotransferase level was at or above the upper limit of the normal range for age.5 Mean values for aspartate aminotransferase and -glutamyltransferase were normal. We therefore suspect that nonalcoholic fatty liver disease and nonalcoholic steatohepatitis are common features in obese and overweight children, even those who are very young. Given that these two disorders are hepatic expressions of the metabolic syndrome, we conclude that this syndrome is as common in young children as it is in older children and adolescents.
Figure 1. Liver-Enzyme Values According to the Degree of Obesity in Young Children.
The values represented by the symbols are means; the I bars represent the 95 percent confidence intervals. Of the patients studied, 37 had a body-mass index (BMI) z score of 1.5 to 2.0, 59 a z score of 2.1 to 2.5, 54 a z score of 2.6 to 3.0, and 32 a z score above 3.0. Liver enzymes were measured (in three laboratories) at 25°C until March 31, 2003, and at 37°C thereafter. To assess the levels before and after the temperature change, data were expressed as the measured value (in units per liter) divided by the upper limit of the normal range for age (in units per liter), which was defined as 2 SD above the mean of the value in a normal population. Values for the upper limit of the normal range for aspartate aminotransferase at 25°C and 37°C were 40 and 82 U per liter, respectively, up to 1 year; 24 and 48 U per liter from 1 to 3 years; 18 and 36 U per liter from 4 to 6 years; and 23 and 47 U per liter from 7 to 12 years. For alanine aminotransferase, the values at 25°C and 37°C were 29 and 54 U per liter, respectively, up to 1 year; 18 and 33 U per liter from 1 to 3 years; 16 and 29 U per liter from 4 to 6 years; and 21 and 39 U per liter from 7 to 12 years. For -glutamyltransferase, the values at 25°C and 37°C were 19 and 34 U per liter, respectively, from 6 to 12 months.
Guido Engelmann, M.D.
Henning Lenhartz, M.D.
Jürgen Grulich-Henn, M.D.
University Children's Hospital
69115 Heidelberg, Germany
guido_engelmann@med.uni-heidelberg.de
References
Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
Ruhl C, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124:71-79.
Harrison S, Di Bisceglie AM. Advances in the understanding and treatment of nonalcoholic fatty liver disease. Drugs 2003;63:2379-2394.
Fishbein MH, Miner M, Mogren C, Chalekson J. The spectrum of fatty liver in obese children and the relationship of serum aminotransferase to severity of steatosis. J Pediatr Gastroenterol Nutr 2003;36:54-61.
Fischbach F, Zawta B. Age dependent reference limits of several enzymes in plasma at different measuring temperatures. Klin Lab 1992;38:555-61.
To the Editor: Weiss and colleagues report a strong clustering of obesity and alterations in glucose metabolism among children and adolescents in whom a range of variables relevant to the metabolic syndrome were measured. Genetic influences, however, were not considered. We studied 30 prepubertal children (18 girls and 12 boys; mean age, 9.1±1.8 years; BMI , 17.8±3.0) who had at least one diabetic parent and 30 children (16 girls and 14 boys; age, 9.0±2.5 years; BMI, 16.6±4.4) who had nondiabetic parents.1 We carried out analyses similar to those performed by Weiss and colleagues, except that we used glycosylated hemoglobin as an integrated marker of glucose metabolism. In factor analysis, the strongest clustering was that of diabetes in at least one parent and glycosylated hemoglobin. Within this factor, the loading for BMI was weak. Although these data are from lean subjects, they suggest that hereditary factors independent of fat mass may influence glucose metabolism in children. Weiss and colleagues may have information on family history that would allow a more precise delineation of the contribution of obesity ("nature vs. nurture") to features of the metabolic syndrome in their subjects.
Timothy M.E. Davis, F.R.A.C.P.
University of Western Australia
6009 Perth, Australia
tdavis@cyllene.uwa.edu.au
Choo Keng Ee, F.R.C.P.
Universiti Malaysia Sarawak
93150 Kuching, Malaysia
References
Davis TME, Ee CK, Bee LK, Hong CP. Clustering of vascular risk factors in the pre-pubertal children of diabetic and non-diabetic Malay adults. Diabetes 2004;53:Suppl 2:A427-A427. abstract.
To the Editor: Weiss et al. report that in 293 young obese subjects, C-reactive protein was related to the degree of obesity but not to the level of insulin resistance or the presence or absence of the metabolic syndrome. In 588 obese children, we observed that C-reactive protein, fibrinogen, and uric acid levels were correlated with standard deviation scores for BMI (with the following respective results: r=0.191, P<0.001; r=0.171, P<0.001; and r=0.244, P<0.001). Only uric acid was associated with insulin resistance (r=0.139, P<0.001) and waist circumference (r=0.335, P<0.01). Mean (±SE) uric acid levels increased in an assessment of insulin resistance based on a homeostasis model (5.9±0.12 vs. 6.1±0.11 vs. 6.5±0.11 mg per deciliter; P<0.001) and with the number of components of the metabolic syndrome (5.9±0.12 vs. 5.9±0.10 vs. 6.7±0.14 vs. 6.8±0.26 mg per deciliter in children with zero, one, two, or three components, respectively; P<0.001). This was not true for C-reactive protein or fibrinogen levels. The prevalence of the metabolic syndrome increased in the groups with progressively higher uric acid levels (16.2 percent vs. 27.2 percent vs. 42.3 percent; P<0.001), but not in the groups with higher C-reactive protein or fibrinogen levels. Uric acid should be considered a marker for risk screening.
Cecilia Invitti, M.D.
Luisa Gilardini, M.D.
Istituto Auxologico Italiano
20145 Milan, Italy
invitti@auxologico.it
Giancarlo Viberti, M.D.
Guy's, King's and St. Thomas' School of Medicine
London SEI 9RT, United Kingdom
The authors reply: We agree with Invitti et al. that their data confirm our results regarding the lack of a relation between C-reactive protein levels and the number of components of the metabolic syndrome in this age group. We did not test uric acid levels in our cohort and thus cannot comment on the findings they present.
Davis and Ee emphasize the important effect of genetic predisposition on glucose metabolism and other components of the metabolic syndrome. According to Davis and Ee's data, the effect of a family history of diabetes clustered with glycosylated hemoglobin more closely than it did with BMI, yet the subjects they studied were not obese. According to our results, a wide range of BMI z scores within the nonobese range has little effect on glucose metabolism; the chief effect is seen in increments within the obese range. Genetic predisposition has been shown to make a significant contribution to features of the metabolic syndrome and may potentially determine vulnerability to the additional burden of obesity. Unfortunately, we had reliable information on family history for only a subgroup of our large cohort and thus did not include it in our analysis.
Engelmann et al. emphasize the potential importance of testing for nonalcoholic fatty liver disease as a component of the metabolic syndrome. Indeed, we have been investigating the prevalence of elevated alanine aminotransferase levels (defined as those above 35 U per liter) in 282 obese children and adolescents. Like Engelmann et al., we found that the degree of obesity was related to the prevalence of elevated alanine aminotransferase levels; 11 percent of the moderately obese subjects and 21 percent of the severely obese subjects had elevated alanine aminotransferase levels (P=0.039). The differences in the definitions of abnormal alanine aminotransferase levels and the significant differences in the age groups studied may explain the lower prevalence rates in our population. We agree that nonalcoholic fatty liver disease is most likely a hepatic manifestation of the metabolic syndrome and thus deserves clinical attention.
Ram Weiss, M.D.
Catherine W. Yeckel, Ph.D.
Sonia Caprio, M.D.
Yale University School of Medicine
New Haven, CT 06512
sonia.caprio@yale.edu
Figure 1. Liver-Enzyme Values According to the Degree of Obesity in Young Children.
The values represented by the symbols are means; the I bars represent the 95 percent confidence intervals. Of the patients studied, 37 had a body-mass index (BMI) z score of 1.5 to 2.0, 59 a z score of 2.1 to 2.5, 54 a z score of 2.6 to 3.0, and 32 a z score above 3.0. Liver enzymes were measured (in three laboratories) at 25°C until March 31, 2003, and at 37°C thereafter. To assess the levels before and after the temperature change, data were expressed as the measured value (in units per liter) divided by the upper limit of the normal range for age (in units per liter), which was defined as 2 SD above the mean of the value in a normal population. Values for the upper limit of the normal range for aspartate aminotransferase at 25°C and 37°C were 40 and 82 U per liter, respectively, up to 1 year; 24 and 48 U per liter from 1 to 3 years; 18 and 36 U per liter from 4 to 6 years; and 23 and 47 U per liter from 7 to 12 years. For alanine aminotransferase, the values at 25°C and 37°C were 29 and 54 U per liter, respectively, up to 1 year; 18 and 33 U per liter from 1 to 3 years; 16 and 29 U per liter from 4 to 6 years; and 21 and 39 U per liter from 7 to 12 years. For -glutamyltransferase, the values at 25°C and 37°C were 19 and 34 U per liter, respectively, from 6 to 12 months.
Guido Engelmann, M.D.
Henning Lenhartz, M.D.
Jürgen Grulich-Henn, M.D.
University Children's Hospital
69115 Heidelberg, Germany
guido_engelmann@med.uni-heidelberg.de
References
Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
Ruhl C, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124:71-79.
Harrison S, Di Bisceglie AM. Advances in the understanding and treatment of nonalcoholic fatty liver disease. Drugs 2003;63:2379-2394.
Fishbein MH, Miner M, Mogren C, Chalekson J. The spectrum of fatty liver in obese children and the relationship of serum aminotransferase to severity of steatosis. J Pediatr Gastroenterol Nutr 2003;36:54-61.
Fischbach F, Zawta B. Age dependent reference limits of several enzymes in plasma at different measuring temperatures. Klin Lab 1992;38:555-61.
To the Editor: Weiss and colleagues report a strong clustering of obesity and alterations in glucose metabolism among children and adolescents in whom a range of variables relevant to the metabolic syndrome were measured. Genetic influences, however, were not considered. We studied 30 prepubertal children (18 girls and 12 boys; mean age, 9.1±1.8 years; BMI , 17.8±3.0) who had at least one diabetic parent and 30 children (16 girls and 14 boys; age, 9.0±2.5 years; BMI, 16.6±4.4) who had nondiabetic parents.1 We carried out analyses similar to those performed by Weiss and colleagues, except that we used glycosylated hemoglobin as an integrated marker of glucose metabolism. In factor analysis, the strongest clustering was that of diabetes in at least one parent and glycosylated hemoglobin. Within this factor, the loading for BMI was weak. Although these data are from lean subjects, they suggest that hereditary factors independent of fat mass may influence glucose metabolism in children. Weiss and colleagues may have information on family history that would allow a more precise delineation of the contribution of obesity ("nature vs. nurture") to features of the metabolic syndrome in their subjects.
Timothy M.E. Davis, F.R.A.C.P.
University of Western Australia
6009 Perth, Australia
tdavis@cyllene.uwa.edu.au
Choo Keng Ee, F.R.C.P.
Universiti Malaysia Sarawak
93150 Kuching, Malaysia
References
Davis TME, Ee CK, Bee LK, Hong CP. Clustering of vascular risk factors in the pre-pubertal children of diabetic and non-diabetic Malay adults. Diabetes 2004;53:Suppl 2:A427-A427. abstract.
To the Editor: Weiss et al. report that in 293 young obese subjects, C-reactive protein was related to the degree of obesity but not to the level of insulin resistance or the presence or absence of the metabolic syndrome. In 588 obese children, we observed that C-reactive protein, fibrinogen, and uric acid levels were correlated with standard deviation scores for BMI (with the following respective results: r=0.191, P<0.001; r=0.171, P<0.001; and r=0.244, P<0.001). Only uric acid was associated with insulin resistance (r=0.139, P<0.001) and waist circumference (r=0.335, P<0.01). Mean (±SE) uric acid levels increased in an assessment of insulin resistance based on a homeostasis model (5.9±0.12 vs. 6.1±0.11 vs. 6.5±0.11 mg per deciliter; P<0.001) and with the number of components of the metabolic syndrome (5.9±0.12 vs. 5.9±0.10 vs. 6.7±0.14 vs. 6.8±0.26 mg per deciliter in children with zero, one, two, or three components, respectively; P<0.001). This was not true for C-reactive protein or fibrinogen levels. The prevalence of the metabolic syndrome increased in the groups with progressively higher uric acid levels (16.2 percent vs. 27.2 percent vs. 42.3 percent; P<0.001), but not in the groups with higher C-reactive protein or fibrinogen levels. Uric acid should be considered a marker for risk screening.
Cecilia Invitti, M.D.
Luisa Gilardini, M.D.
Istituto Auxologico Italiano
20145 Milan, Italy
invitti@auxologico.it
Giancarlo Viberti, M.D.
Guy's, King's and St. Thomas' School of Medicine
London SEI 9RT, United Kingdom
The authors reply: We agree with Invitti et al. that their data confirm our results regarding the lack of a relation between C-reactive protein levels and the number of components of the metabolic syndrome in this age group. We did not test uric acid levels in our cohort and thus cannot comment on the findings they present.
Davis and Ee emphasize the important effect of genetic predisposition on glucose metabolism and other components of the metabolic syndrome. According to Davis and Ee's data, the effect of a family history of diabetes clustered with glycosylated hemoglobin more closely than it did with BMI, yet the subjects they studied were not obese. According to our results, a wide range of BMI z scores within the nonobese range has little effect on glucose metabolism; the chief effect is seen in increments within the obese range. Genetic predisposition has been shown to make a significant contribution to features of the metabolic syndrome and may potentially determine vulnerability to the additional burden of obesity. Unfortunately, we had reliable information on family history for only a subgroup of our large cohort and thus did not include it in our analysis.
Engelmann et al. emphasize the potential importance of testing for nonalcoholic fatty liver disease as a component of the metabolic syndrome. Indeed, we have been investigating the prevalence of elevated alanine aminotransferase levels (defined as those above 35 U per liter) in 282 obese children and adolescents. Like Engelmann et al., we found that the degree of obesity was related to the prevalence of elevated alanine aminotransferase levels; 11 percent of the moderately obese subjects and 21 percent of the severely obese subjects had elevated alanine aminotransferase levels (P=0.039). The differences in the definitions of abnormal alanine aminotransferase levels and the significant differences in the age groups studied may explain the lower prevalence rates in our population. We agree that nonalcoholic fatty liver disease is most likely a hepatic manifestation of the metabolic syndrome and thus deserves clinical attention.
Ram Weiss, M.D.
Catherine W. Yeckel, Ph.D.
Sonia Caprio, M.D.
Yale University School of Medicine
New Haven, CT 06512
sonia.caprio@yale.edu