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      Trabecular Bone Mineral Density and Bone Geometry of the Distal Radius at Completion of Pubertal Growth in Childhood Type 1 Diabetes

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          Abstract

          Aim: To identify disease-related risk factors for an altered bone mineral density (BMD) and geometry at young adulthood in patients with diabetes mellitus type 1 (DM1). Methods: Fifty-six DM1 patients (23 females, 33 males) with prepubertal onset of diabetes were studied after completion of skeletal growth. Bone parameters at the distal radius were investigated by peripheral quantitative computed tomography. Disease-related parameters, in particular average HbA1c during the 2 years around peak height velocity, were analyzed. Forty-seven healthy controls (32 females, 15 males) were studied. Results: Trabecular BMD was similar between DM1 patients and controls. The mean (±SD) cross-sectional bone area (CSA) was smaller in DM1 patients compared to controls (282.5 ± 45.4 vs. 326.7 ± 52.2 mm<sup>2</sup>, p = 0.002 and males 391.0 ± 61.3 vs. 423.4 ± 81.9 mm<sup>2</sup>, p = 0.1). In female DM1 patients, the CSA z-score correlated negatively with the body mass index z-score (r = -0.52, p = 0.01) and positively with the height z-score (r = 0.49, p = 0.02). Conclusions: DM1 patients are at risk for smaller bone sizes at the distal radius at the end of pubertal growth, especially females with increased adiposity. Diabetes-specific parameters seem to have a low impact on forearm volumetric apparent mineral density.

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          Most cited references21

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          Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes.

          Patients with insulin-dependent diabetes mellitus often have poor metabolic control during puberty. To determine whether puberty is associated with decreased insulin-stimulated glucose metabolism, we compared the results of euglycemic insulin-clamp studies in adults and prepubertal and pubertal children with and without insulin-dependent diabetes. In nondiabetic pubertal children, insulin-stimulated glucose metabolism (201 +/- 12 mg per square meter of body surface area per minute) was sharply reduced, as compared with that of prepubertal children and adults (316 +/- 34 and 290 +/- 21 mg per square meter, respectively; P less than 0.01), despite comparable hyperinsulinemia (insulin levels of 80 to 90 microU per milliliter). Similarly, the response to insulin was 25 to 30 percent lower in the diabetic pubertal children than in the diabetic prepubertal children (P less than 0.05) and adults (P = 0.07). At each stage of development, the stimulating effect of insulin on glucose metabolism was decreased by 33 to 42 percent in the children with diabetes (P less than 0.01). In all the groups of children studied, the response to insulin was inversely correlated with mean 24-hour levels of growth hormone (r = -0.52, P = 0.01). Among the diabetic children, the glycosylated hemoglobin levels were substantially higher in the pubertal children than in the prepubertal children (P less than 0.02), although the daily insulin doses tended to be higher. These data suggest that insulin resistance occurs during puberty in both normal children and children with diabetes. The combined adverse effects of puberty and diabetes on insulin action may help explain why control of glycemia is so difficult to achieve in adolescent patients.
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            References for growth and pubertal development from birth to 21 years in Flanders, Belgium.

            Due to the secular trend in length and height, growth references need to be updated regularly. Reference charts that were until recently used in Belgium are based on samples collected more than 30 years ago, and references for body mass index (BMI) and pubertal development have not been established before. To establish contemporary cross-sectional reference charts for height, weight, BMI, head circumference, and pubertal development from birth to 21 years of age, based on a representative sample of children from Flanders, Belgium. 15 989 healthy subjects of Belgian origin, 0-25 years of age, were measured in 2002-2004. Growth curves were fitted with the LMS method, and percentiles for the pubertal development were estimated with generalized additive models on status quo data from 8690 subjects aged 6-22 years of age. A positive secular trend in height and weight is observed in children above 5 years of age. Adult median height has increased by 1.2 cm/decade in boys and 0.8 cm/decade in girls; median weight by 0.9 kg/decade in boys, and 1.0 kg/decade in girls, and the weight distribution became more skewed. The BMI curve is comparable to that of other populations, except for higher percentiles. This reflects the increasing prevalence of overweight and obesity. Median age at menarche (13.0 years) has not advanced any more over the past 50 years. Median ages at menarche and B2 in girls and G2 or T4 in boys are comparable to other West European estimates, but approximately 10% enter G2/T4 before 9 years of age. The ongoing secular trend in height and weight makes growth charts previously used in Belgium obsolete. New representative charts for growth and pubertal development are introduced. For weight monitoring, it is advised that the now-available BMI growth charts are used.
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              Bone densities and bone size at the distal radius in healthy children and adolescents: a study using peripheral quantitative computed tomography.

              Peripheral quantitative computed tomography (pQCT) has the ability to improve the diagnostic utility of densitometry in children and adolescents, because bone size and volumetric bone mineral density (vBMD) can be measured independently. Nevertheless, detailed reference data are lacking. We therefore performed pQCT (XCT-2000 scanner, Stratec, Inc., Pforzheim, Germany) at the distal radius in 371 healthy children, adolescents, and young adults (185 males and 186 females, ages 6-23 years) and in 107 of their parents (19 men and 88 women, ages 29-40 years). Total vBMD, trabecular, and "cortical + subcortical" vBMD as well as cross-sectional area (CSA) were determined at the "4% site" of the distal radius. This location was defined as the site whose distance to the most distal portion of the growth plate or to the radial articular surface corresponded to 4% of the forearm length. In both genders, total vBMD remained stable between 6 and 15 years of age and then increased by 30% in girls and by 46% in boys. Regarding pubertal development, total vBMD remained almost constant throughout pubertal stages 1-4 and thereafter increased in both genders. Trabecular vBMD did not change with age in girls, whereas in boys an increase with age of about 10% was noted after 15 years of age. Males had higher trabecular vBMD than females. This gender difference increased from 6% in prepubertal children to 23% in adults. The variation with age and pubertal stage in "cortical + subcortical" vBMD-cort was similar to that of total vBMD. CSA roughly doubled between 6 and 15 years of age in both genders. In conclusion, the availability of this reference material will provide a basis for the use of pQCT in the assessment of pediatric bone diseases.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2013
                March 2013
                05 February 2013
                : 79
                : 2
                : 68-74
                Affiliations
                Departments of aPediatrics and bRadiology, UZ Brussel, Brussels, Belgium
                Author notes
                *Jean De Schepper, Department of Pediatrics, Laarbeeklaan 101, BE-1090 Brussels (Belgium), E-Mail jean.deschepper@uzbrussel.be
                Article
                346686 Horm Res Paediatr 2013;79:68-74
                10.1159/000346686
                23391966
                5ea3e634-35c9-4e55-bb4f-bc8464717daf
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 05 June 2012
                : 20 December 2012
                Page count
                Figures: 3, Tables: 3, Pages: 7
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Bone mineral density,Type 1 diabetes mellitus,Glycemic control,Peripheral quantitative computed tomography ,Adolescence

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