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

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          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


                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                March 2004
                26 March 2004
                : 61
                : 4
                : 176-179
                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
                76135 Horm Res 2004;61:176–179
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 1, References: 37, Pages: 4
                Original Paper


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