Correspondence
Correction
Impaired Glucose Tolerance in Obese Children and Adolescents
N Engl J Med 2002; 347:290-292July 25, 2002
- Article
To the Editor:
The report by Sinha et al. (March 14 issue)1 provides important and timely information about the association between impaired glucose tolerance and obesity in children. However, it is important to note that the study sample was derived from a clinic population that may not be the most representative sample suitable for deriving prevalence estimates. Moreover, it is interesting to note that in 1968 Paulsen et al.2 reported a very similar finding. Using the same criteria of the American Diabetes Association (ADA) used by Sinha et al. in 2002, Paulsen et al. reported that 17 percent of the 66 obese children they studied had impaired glucose tolerance, and 6 percent met the criteria for type 2 diabetes.
Thus, the association of obesity with impaired glucose tolerance and type 2 diabetes in children may not be a new phenomenon. However, the number of obese children is increasing rapidly, especially in some ethnic groups.3 Thus, the absolute number of children in the population who have impaired glucose tolerance and type 2 diabetes is increasing because of the increased numbers of obese children. Future research should focus on why an accumulation of excess body fat becomes detrimental to health. Public health efforts should focus on reducing the prevalence of obesity among children, since this factor alone is likely to have a major effect on the current and future risk of type 2 diabetes.
3 ReferencesMichael I. Goran, Ph.D.
University of Southern California, Los Angeles, CA 90033
goran@usc.edu 1
Sinha R ,Fisch G ,Teague B , et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002;346:802-810[Erratum, N Engl J Med 2002;346:1756.]
Full Text | Web of Science | Medline2
Paulsen EP ,Richenderfer L ,Ginsberg-Fellner F . Plasma glucose, free fatty acids, and immunoreactive insulin in sixty-six obese children: studies in reference to a family history of diabetes mellitus. Diabetes 1968;17:261-269
Web of Science | Medline3
Strauss RS ,Pollack HA . Epidemic increase in childhood overweight, 1986-1998. JAMA 2001;286:2845-2848
CrossRef | Web of Science | Medline
To the Editor:
Sinha et al. report that the prevalence of impaired glucose tolerance was 25 percent in children (4 to 10 years old), which was similar to the prevalence in the group of adolescents studied, who should also have had insulin resistance of puberty,1 making impaired glucose tolerance more likely. Although the purpose of this study was not only to determine the prevalence of impaired glucose tolerance, these prevalence data were given prominence in the abstract and discussion. We suggest that the unexpectedly high prevalence of impaired glucose tolerance in the group of children who were 4 to 10 years old may be due to referral bias in favor of extremely overweight children, who may have already had evidence of dysmetabolic syndrome X.
We evaluated glucose tolerance in substantially overweight black children and white children (6 to 11 years old) who were recruited from the local community and whose parents were not seeking treatment for the weight problem. The prevalence of impaired glucose tolerance was much lower in this group of children (4.1 percent; 95 percent confidence interval, 2 to 9 percent), even though they had significantly greater insulin resistance and a significantly higher index of beta-cell function than did children who were not overweight (Table 1Table 1
Results of Metabolic Studies in Overweight Children and Children of Normal Weight Who Were Recruited from the Community.). An evaluation of children in our cohort who had a mean (±SD) body-mass index of 32±5 (calculated as the weight in kilograms divided by the square of the height in meters), which was similar to the mean value in the cohort described by Sinha et al., showed that only 3 of 48 children had impaired glucose tolerance (6.3 percent; 95 percent confidence interval, 1 to 17 percent).5 ReferencesGabriel I. Uwaifo, M.D.
Jane Elberg, B.S.
Jack A. Yanovski, M.D., Ph.D.
National Institutes of Health, Bethesda, MD 20892
uwaifog@mail.nih. gov 1
Amiel SA ,Caprio S ,Sherwin RS ,Plewe G ,Haymond MW ,Tamborlane WV . Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab 1991;72:277-282
CrossRef | Web of Science | Medline2
Must A ,Dallal GE ,Dietz WH . Reference data for obesity: 85th and 95th percentiles of body mass index (wt/ht2) and triceps skinfold thickness. Am J Clin Nutr 1991;53:839-846[Erratum, Am J Clin Nutr 1991;54:773.]
Web of Science | Medline3
Sinha R ,Fisch G ,Teague B , et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002;346:802-810[Erratum, N Engl J Med 2002;346:1756.]
Full Text | Web of Science | Medline4
Katz A ,Nambi SS ,Mather K , et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402-2410
CrossRef | Web of Science | Medline5
Kosaka K ,Hagura R ,Kuzuya T . Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose tolerance but later developed definite diabetes. Diabetes 1977;26:944-952
Web of Science | Medline
To the Editor:
We have recently studied the prevalence of impaired glucose tolerance and the relation between cardiovascular risk factors and levels of glycemia in 710 grossly obese Italian children and adolescents (age range, 6 to 18 years; mean age, 14 years; standard-deviation score for body-mass index, 3.8±0.7), all of whom were of European origin for at least two generations. The frequency of impaired glucose tolerance and of type 2 diabetes was 4.5 percent and 0.1 percent, respectively — figures that are consistently lower than those reported by Sinha et al. in their cohort of obese American children. The obese Italian children had considerably lower values for insulin resistance, calculated by homeostatic model assessment, than their American counterparts. In a multivariate analysis, glucose values measured two hours after an oral glucose dose (1.75 g per kilogram) were significantly and independently related to insulin resistance (P<0.001) and to insulin secretion, measured as the insulinogenic index (P<0.001), suggesting that both an impaired insulin response and reduced insulin sensitivity contributed to the hyperglycemia in the Italian children. We believe that differences in ethnic background and in lifestyle and dietary habits may account for the striking disparity in the prevalence of impaired glucose tolerance between these two cohorts of obese children.
Cecilia Invitti, M.D.
Luisa Gilardini, M.D.
Istituto Auxologico Italiano, 20145 Milan, Italy
invitti@auxologico.it Giancarlo Viberti, M.D.
Guy's Hospital, London SE1 9RT, United KingdomTo the Editor:
It would be helpful if Sinha and colleagues would comment on the usefulness of screening 22 million obese children worldwide with an oral glucose-tolerance test rather than a simpler and less expensive method. Table 2 of their report shows a significant difference in the fasting insulin level between obese children and adolescents with normal glucose tolerance and those with impaired glucose tolerance. If this difference is consistent and reproducible, why not use the insulin-resistance index as a screening tool?
Phyllis W. Speiser, M.D.
Schneider Children's Hospital, New Hyde Park, NY 11042
pspeiser@lij.edu To the Editor:
The findings reported by Sinha et al. provide strong evidence that, even in childhood, obesity with its associated conditions represents an epidemic with substantial effects on public health. In the accompanying editorial by Rocchini,1 the final paragraph, on effective strategies to combat obesity-related diabetes, contains a statement that concerns me. Rocchini notes that the prevention of obesity is an obvious strategy but states that “despite all our best efforts, prevention of childhood obesity eludes our grasp.” Rocchini suggests that a more effective strategy would be to identify obese children who are at high risk for diabetes on the basis of oral glucose-tolerance testing and to target them for intensive weight-loss treatment.
In my opinion, the solution to the obesity epidemic must be based on much broader public health and clinical strategies. The time has come to develop comprehensive national obesity-prevention programs that include educational, behavioral, and environmental components analogous to those already in place for tobacco use. Examples of effective prevention programs that focus on children and adolescents are school-based interventions designed to increase physical activity and consumption of healthier foods and home-based interventions designed to reduce television viewing.2,3 Physicians and other health care professionals, elected officials, educators, and parents need to recognize the impact of this major health problem and have the will and energy to correct it through preventive approaches.
3 ReferencesHannes Gaenzer, M.D.
University of Innsbruck, A-6020 Innsbruck, Austria
hannes.gaenzer@uibk. ac. at 1
Rocchini AP . Childhood obesity and a diabetes epidemic. N Engl J Med 2002;346:854-855
Full Text | Web of Science | Medline2
Gortmaker SL ,Peterson K ,Wiecha J , et al. Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health. Arch Pediatr Adolesc Med 1999;153:409-418
Web of Science | Medline3
Robinson TN . Reducing children's television viewing to prevent obesity: a randomized controlled trial. JAMA 1999;282:1561-1567
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Caprio replies:
To the Editor: I agree with Dr. Goran that prevalence rates are best derived from non–clinic-based samples. Of note is the recent school-based study by Grey et al.,1 involving 42 obese adolescents whose parents were not seeking treatment. In this group, the prevalence of impaired glucose tolerance was 21.4 percent, and the prevalence of type 2 diabetes was 4.6 percent — findings that are very similar to ours. I disagree with Dr. Goran's statement that our findings were very similar to those reported by Paulsen et al. in 1968; they did not use the same ADA definitions that we used. When we recalculated the prevalence of impaired glucose tolerance in their study using the ADA criteria that we had used in our study, impaired glucose tolerance was present in 11 percent of the children, and 6 percent had type 2 diabetes mellitus.
The low prevalence of impaired glucose tolerance (6.3 percent) reported by Uwaifo et al. in obese children recruited from the community is probably due to a low insulin-resistance index. In fact, the mean insulin-resistance index in their obese children was 3.4±2.7, whereas in our children it was 5±0.6 in children with normal glucose tolerance and 7.2±1 in those with impaired glucose tolerance.
Interestingly, Invitti et al. report that the cohort of children they studied, although grossly obese, had a considerably lower insulin-resistance index than our obese American cohort. As in our study, insulin resistance was found to be strongly and independently related to the glucose level at two hours. However, in contrast to our findings, the insulinogenic index was related to the glucose level at two hours. It is conceivable that our cohort was not large enough for us to detect differences in beta-cell function in patients with impaired glucose tolerance. We concur that differences in insulin resistance related to ethnic background and lifestyle may explain the striking disparity in the prevalence of impaired glucose tolerance between the two cohorts.
In response to Dr. Speiser's two important questions: we suggest that children with marked obesity undergo screening for fasting hyperinsulinemia and other features of the metabolic syndrome. The reproducibility of the insulin-resistance index (determined by homeostatic model assessment) is not known and varies greatly according to the method used to measure insulin and glucose levels. Furthermore, its predictive value in children needs to be determined.
We would also like to note that in our report, the values for proinsulin and for the ratio of proinsulin to insulin on page 806 and in Figure 2 are incorrect. All reported values for proinsulin and for the ratio of proinsulin to insulin should be divided by a factor of 10. In addition, the second part of the last sentence of the legend to Figure 2 should read, “to convert values for proinsulin to picomoles per liter, divide by 0.00939.”
1 ReferencesSonia Caprio, M.D.
Yale School of Medicine, New Haven, CT 06520-8064
sonia.caprio@yale. edu Author/Editor Response
The editorialist replies:
To the Editor: There are two commonly used strategies to combat a major public health problem such as adolescent obesity. One is a population-based strategy, as suggested by Dr. Gaenzer. The other strategy is to identify persons at high medical risk (e.g., obese adolescents with impaired glucose tolerance) and target them for disease-specific therapy. The population-based strategy works well when the program is both effective in preventing or curing the problem and low in cost. An excellent example of an outstanding population-based strategy is the use of vaccinations to prevent childhood diseases. However, there is no effective low-cost treatment for childhood obesity. I agree with Dr. Gaenzer that the time has come to develop comprehensive national obesity-prevention programs similar to programs aimed at tobacco use. However, until we have a prevention program that has been proved to reduce the incidence of childhood obesity significantly, I stand by my recommendation to identify obese children who are at high risk for diabetes and target them for intensive weight-loss treatment.
Albert P. Rocchini, M.D.
University of Michigan Medical Center, Ann Arbor, MI 48109
rocchini@med.umich. edu - Citing Articles (8)
Citing Articles
1
Ebe D'Adamo, Nicola Santoro, Sonia Caprio. (2011) Metabolic Syndrome in Pediatrics: Old Concepts Revised, New Concepts Discussed. Pediatric Clinics of North America 58:5, 1241-1255
CrossRef2
Lana M Bell, Jacqueline A Curran, Sue Byrne, Heather Roby, Katie Suriano, Timothy W Jones, Elizabeth A Davis. (2011) High incidence of obesity co-morbidities in young children: A cross-sectional study. Journal of Paediatrics and Child Healthno-no
CrossRef3
Ebe D'Adamo, Nicola Santoro, Sonia Caprio. (2009) Metabolic Syndrome in Pediatrics: Old Concepts Revised, New Concepts Discussed. Endocrinology & Metabolism Clinics of North America 38:3, 549-563
CrossRef4
T H Inge, S A Xanthakos, M H Zeller. (2007) Bariatric surgery for pediatric extreme obesity: now or later?. International Journal of Obesity 31:1, 1-14
CrossRef5
Dee Pei, Chin-Fu Hsiao, Yi-Jen Hung, Chang-Hsun Hsieh, Sandra-Chi Fang, Wei-Chen Lian, Wen-Lin Hsu, Chen-Chung Fu, Hsin-Dean Chen, Shi-Wen Kuo. (2006) The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese. Diabetes/Metabolism Research and Reviews 22:1, 26-33
CrossRef6
LS Conwell, JA Batch. (2004) Oral glucose tolerance test in children and adolescents: Positives and pitfalls. Journal of Paediatrics and Child Health 40:11, 620-626
CrossRef7
Julia Steinberger. (2003) Diagnosis of the metabolic syndrome in children. Current Opinion in Lipidology 14:6, 555-559
CrossRef8
D. M. Barton, V. Baskar, D. Kamalakannan, H. N. Buch, K. Gone, E. Wilson, J. Anderson, T. A. M. Abdu. (2003) An assessment of care of paediatric and adolescent patients with diabetes in a large district general hospital. Diabetic Medicine 20:5, 394-398
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