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      Type 2 Diabetes mellitus in Children and Adolescents: A Review from a European Perspective

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          Abstract

          Changes in food consumption and exercise are fuelling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development, an increasing rate of type 2 diabetes mellitus has been recorded in children and adolescents in the USA and, more recently, in many countries around the world. Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Lower susceptibility in white Caucasians and higher susceptibility in Asians, Hispanics and blacks have been noted. There is a high hidden prevalence and a lack of exact data on the epidemiology of the disease in Europe: in Germany only 70 patients below the age of 15 years were identified in the systematic, nationwide DPV (Diabetessoftware für prospektive Verlaufsdokumentation) diabetes survey, but our calculations suggest that more than 5000 young people in Germany at present would meet the diagnostic criteria of type 2 diabetes. In Australasia, the prevalence of type 2 diabetes is reportedly high in some ethnic groups and again is linked very closely to the obesity epidemic. No uniform and evidence-based treatment strategy is available: many groups use metformin, exercise programmes and nutritional education as a comprehensive approach to treat type 2 diabetes in childhood and adolescence. The lack of clear epidemiological data and a strong need for accepted treatment strategies point to the key role of preventive programmes. Prevention of obesity will help to counteract the emerging worldwide epidemic of type 2 diabetes in youth. Preventive programmes should focus on exercise training and reducing sedentary behaviour such as television viewing, encouraging healthy nutrition and supporting general education programmes since shorter school education is clearly associated with higher rates of obesity and hence the susceptibility of an individual to acquire type 2 diabetes.

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          Most cited references 10

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          Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.

          Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents. All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose. Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance. Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.
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            Epidemic increase in childhood overweight, 1986-1998.

            Overweight is the most common health problem facing US children. Data for adults suggest that overweight prevalence has increased by more than 50% in the last 10 years. Data for children also suggest that the prevalence of overweight continues to increase rapidly. To investigate recent changes in the prevalence of overweight within a nationally representative sample of children. The National Longitudinal Survey of Youth, a prospective cohort study conducted from 1986 to 1998 among 8270 children aged 4 to 12 years (24 174 growth points were analyzed). Prevalence of overweight children, defined as body mass index (BMI) greater than the 95th percentile for age and sex, and prevalence of overweight and at-risk children, defined as BMI greater than the 85th percentile for age and sex. The roles of race/ethnicity, sex, income, and region of residence were also examined. Between 1986 and 1998, overweight increased significantly and steadily among African American (P<.001), Hispanic (P<.001), and white (P =.03) children. By 1998, overweight prevalence increased to 21.5% among African Americans, 21.8% among Hispanics, and 12.3% among non-Hispanic whites. In addition, overweight children were heavier in 1998 compared with 1986 (P<.001). After adjusting for confounding variables, overweight increased fastest among minorities and southerners, creating large demographic differences in the prevalence of childhood overweight by 1998. The number of children with BMI greater than the 85th percentile increased significantly from 1986 to 1998 among African American and Hispanic children (P<.001 for both) and nonsignificantly among white children (P =.77). Childhood overweight continues to increase rapidly in the United States, particularly among African Americans and Hispanics. Culturally competent treatment strategies as well as other policy interventions are required to increase physical activity and encourage healthy eating patterns among children.
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              Beneficial effects of metformin in normoglycemic morbidly obese adolescents.

              Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals. It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults. To evaluate the antiobesity effect of metformin, we conducted a randomized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents (body mass index [BMI] >30 kg/m(2)). All subjects were placed on a low-calorie (1,500 kcal for women and 1,800 kcal for men) meal plan. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 15.6 +/- 0.4 and 41.2 +/- 1.8, respectively) received metformin (850 mg twice daily) for 8 weeks, and 12 subjects (mean +/- SE for age and BMI, 15.7 +/- 0.5 and 40.8 +/- 1.4, respectively) received placebo. Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P <.01), greater decrease in body fat (P <.001), greater increase in fat-free mass to body fat ratio (P <.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P <.001). This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P <.01). This corresponded to a significant reduction in plasma leptin (P <.005), cholesterol, triglycerides, and free fatty acid (FFA) levels (P <.05) only in the metformin-treated subjects. Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone. Copyright 2001 by W.B. Saunders Company
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-7539-3
                978-3-318-00942-2
                1663-2818
                1663-2826
                2003
                January 2003
                17 November 2004
                : 59
                : Suppl 1
                : 77-84
                Affiliations
                aHospital for Children and Adolescents, University of Leipzig, and bMedical Department III, University Hospital, Leipzig, and cChildren’s Hospital, University of Ulm, Ulm, Germany
                Article
                67829 Horm Res 2003;59(suppl 1):77–84
                10.1159/000067829
                12566725
                © 2003 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.

                Page count
                Figures: 2, Tables: 5, References: 59, Pages: 8
                Categories
                Type 2 Diabetes in Childhood

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