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      Altered Distribution of the Debrisoquine Oxidative Phenotypes in Children with Type 1 Diabetes mellitus

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          Abstract

          Objective: The recently observed increase in the incidence of type 1 diabetes mellitus (Type 1 DM) suggests a major role of environmental factors in the etiopathogenesis of the disease. The individual variation in cytochrome P<sub>450</sub>IID6 may influence the individual susceptibility to environmentally linked diseases. We aimed to evaluate the prevalence of cytochrome P<sub>450</sub>IID6 phenotypes in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n = 100). Methods: Debrisoquine was administered orally and debrisoquine hydroxylation phenotype was determined as a metabolic ratio of urinary recovered debrisoquine and 4-hydroxydebrisoquine. Results: Eight of the 100 healthy subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome P<sub>450</sub>IID6 poor metabolizer phenotype (metabolic ratio ≧12.6). Conclusion: Cytochrome P<sub>450</sub>IID6’s activity may play a role in the development of Type 1 DM.

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          Most cited references 7

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          Putative environmental factors in Type 1 diabetes.

           M Knip,  H. Åkerblom (1998)
          Various environmental triggers, e.g. certain viruses and dietary factors, are thought to initiate the autoimmune process, leading to the destruction of pancreatic beta-cells and consequent Type 1 diabetes. A genetic predisposition is another prerequisite allowing the autoimmune process to progress. Twin studies, major geographical variations in incidence rates, temporal trends in the incidence and findings in migrant studies indicate that environmental factors play a crucial role in the development of Type 1 diabetes. In the present review the major focus is on dietary factors, and among them particularly the possible role of cow's milk proteins. The cow's milk and Type 1 diabetes hypothesis was developed more than 10 years ago, and the issue is still not settled. Among viral infections, enteroviruses are today the most interesting group of viruses in this respect, as recent prospective studies indicate that these viruses may trigger and potentiate existing beta-cell autoimmunity. Among toxins, particularly N-nitroso compounds are of potential interest, as they are probably involved in the aetiology of some cases. Finally, psychosocial factors and the interaction between genetic predisposition and environmental factors are briefly discussed.
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            Determination of debrisoquine and its 4-hydroxy metabolite in biological fluids by gas chromatography with flame-ionization and nitrogen-selective detection

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              “It's the genes, stupid” Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism

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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
                1663-2818
                1663-2826
                2004
                March 2004
                26 March 2004
                : 61
                : 4
                : 176-179
                Affiliations
                aFirst Department of Paediatrics, Semmelweis University, Budapest; bSecond Department of Paediatrics, Postgraduate University of Budapest and Children’s Health Center, Miskolc County Hospital, Miskolc, Hungary
                Article
                76135 Horm Res 2004;61:176–179
                10.1159/000076135
                14726620
                © 2004 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: 1, References: 37, Pages: 4
                Categories
                Original Paper

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