Published online May 2, 2005
PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1441-1442 (doi:10.1542/peds.2005-0251)

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Improvement of Glucose Homeostasis After Weight Loss in Obese Children: In Reply

Thomas Reinehr, MD
Werner Andler, MD
Vestische Kinder- und Jugendklinik
University of Witten/Herdecke
45711 Datteln, Germany

Wieland Kiess, MD
Thomas Kapellen, MD
Hospital for Children and Adolescents
University of Leipzig
04317 Leipzig, Germany

In Reply.—

We are grateful to Santoro et al for their comments and for sharing their data with us. We totally agree with their general concept and conclusion. However, it is difficult to compare our data¹ with theirs. Santoro et al used other BMI percentiles (which were not defined) to define the degree of overweight than we did, because the mean SD score (SDS) BMI at baseline was 5.0 in their study. In our study, consisting of obese and extremely obese children, the median SDS BMI was 2.2. Overweight is defined by an SDS BMI of >1.3, obesity is defined by an SDS BMI of >1.9, and extreme obesity is defined by an SDS BMI of >2.3 in the percentiles underlying our study.² Furthermore, if the LMS method is not used to calculate SDS BMI, the effect of weight reduction could be overestimated in the study of Santoro et al compared with our study, because BMI percentiles are not distributed normally. Therefore, only relative changes and not absolute changes of SDS BMI can be compared between the data of Santoro et al and our data.

The clinical data of Santoro et al demonstrate that a reduction of 30% of overweight leads to a clinically relevant improvement in insulin sensitivity in obese children with impaired glucose tolerance, in concordance with our study in obese children.¹ A reduction of >30% overweight (median decrease SDS BMI: 0.88; baseline median SDS BMI; 2.74) (see Table 1) is also associated with a relevant improvement of insulin sensitivity in overweight children with type 2 diabetes mellitus.³ Diagnosis of type 2 diabetes mellitus was established in these white children by the criteria of the American Diabetes Association⁴: fasting plasma glucose of >126 mg/dL (7.0 mmol/L) and/or >200 mg/dL (11.1 mmol/L) after 2 hours in the oral glucose-tolerance test by repeated testing on different days. Autoantibodies were negative in all patients. The degree of overweight (SDS BMI) was calculated on the basis of the German percentiles and the LMS method.² The insulin-resistance index (calculated by using the homeostasis model assessment [HOMA-IR]) was determined by the following formula: HOMA-IR = (insulin [mU/L] x glucose [mmol/L])/22.5. Weight loss was achieved in the patients by physical exercise, a low-fat, high-carbohydrate diet, and behavioral therapy. Of the 5 children losing weight, 4 (patients 1, 3, 4, and 5) were initially treated with metformin over 6 months and none with insulin. None of the patients needed medication after weight loss.

View this table: [in this window] [in a new window]   TABLE 1. Weight Status and Glucose Metabolism at Baseline and in Follow-up in 5 Children With Type 2 Diabetes Mellitus

 
An important question is how adipose tissue can lead to insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. The adipose tissue–derived hormones adiponectin, visfatin, and leptin are thought to be the link between insulin resistance and adipose tissue.^5,6 Although increasing leptin levels are hypothesized to impair insulin sensitivity, decreasing adiponectin levels are postulated to decrease insulin sensitivity. In the meanwhile, we could demonstrate in additional studies of obese children that a reduction of >0.5 SDS BMI (30% reduction of the overweight) was associated with a significant increase in adiponectin concentrations and a significant decrease in leptin levels parallel to an improvement of insulin sensitivity.^7,8 These findings integrate with the clinical data of improvement in insulin sensitivity resulting from a reduction of overweight by >30%.

We have to keep in mind that the sample sizes in the Santoro et al study and of our diabetic patients are very small. Probably a lower degree of weight loss will lead to significant improvement of insulin sensitivity in larger collectives, as well. However, we can conclude that at least a reduction of 30% overweight or 0.5 SDS BMI based on the German BMI percentile² (which is a reduction of BMI of 2 or a stable weight over a 1-year period among growing children) is associated with a clinically relevant improvement of insulin sensitivity in obese children, obese children with impaired glucose tolerance, and obese children with type 2 diabetes mellitus.

REFERENCES

1. Reinehr T, Kiess W, Kapellen T, Andler W. Insulin sensitivity among obese children and adolescents, according to degree of weight loss. Pediatrics. 2004;114 :1569 –1573[Abstract/Free Full Text]
2. Kromeyer-Hauschild K, Wabitsch M, Geller F, et al. Percentiles of body mass index in children and adolescents evaluated from different regional German studies. Monatsschr Kinderheilkd. 2001;149 :807 –818[CrossRef]
3. Reinehr T, Andler W, Kapellen T, et al. Clinical characteristics of type 2 diabetes mellitus in overweight European Caucasian adolescents. Exp Clin Endocrinol Diabetes. 2005: In press
4. American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care. 2000;23 :381 –389[Web of Science][Medline]
5. Stefan N, Stumvoll M. Adiponectin—its role in metabolism and beyond. Horm Metab Res. 2002;34 :469 –474[CrossRef][Web of Science][Medline]
6. Hug C, Lodish HV. Visfatin: a new adipokine. Science. 2005;307 :366 –367[Abstract/Free Full Text]
7. Reinehr T, Roth C, Menke T, Andler W. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab. 2004;89 :3790 –3794[Abstract/Free Full Text]
8. Reinehr T, Roth CL, Alexy U, Kersting M, Kiess W, Andler W. Ghrelin levels before and after reduction of overweight due to a low fat high carbohydrate diet in obese children and adolescents. Int J Obes. 2005: In press

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PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics

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Improvement of Glucose Homeostasis After Weight Loss in Obese Children

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Related articles in Pediatrics Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Reinehr, T. Articles by Kapellen, T. Search for Related Content PubMed PubMed Citation Articles by Reinehr, T. Articles by Kapellen, T. Related Collections Endocrinology Social Bookmarking                         What's this?