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Genetische Studien zum Typ-2-Diabetes

Mögliche Implikationen für Prävention und Therapie

Genetic studies on type 2 diabetes

Potential implications for prevention and therapy

  • Leitthema
  • Published:
Der Diabetologe Aims and scope

Zusammenfassung

Die genomweiten Assoziationsstudien der letzten Jahre haben gezeigt, dass viele Gene mit schwachen Effekten zum Risiko für den Typ-2-Diabetes beitragen. Die bislang bekannten Risikogene erklären 5–10% der genetischen Prädisposition. Obwohl die Kombination von Genotypdaten zeigt, dass Personen mit vielen Risikoallelen ein höheres Diabetesrisiko haben als Personen mit weniger Risikoallelen, können genetische Tests zurzeit die Prädiktion durch einfache anthropometrische und klinische Daten zwar statistisch signifikant, aber nicht klinisch relevant verbessern. Die genetischen Erkenntnisse untermauern die Hypothese, dass in der Entstehung des Typ-2-Diabetes eine genetisch programmierte Betazelldysfunktion und eine durch Umwelt- und Lebensstilfaktoren ausgelöste Insulinresistenz zusammenwirken. Erste Studien legen nahe, dass das genetische Risiko durch Lebensstilintervention modifiziert wird und dass Genvarianten einen Einfluss auf den Therapieerfolg mit bestimmten Pharmaka haben können. Ein besseres Verständnis der Genetik wird eine präzisere Aufklärung der molekularen Pathogenese des Typ-2-Diabetes erlauben und bei der Entdeckung neuer Angriffspunkte für pharmakologische Therapien helfen.

Abstract

Recent genomewide association studies revealed that many genes with weak or moderate effects contribute to the risk of type 2 diabetes. The risk genes that are known so far explain 5%–10% of the genetic predisposition. Although the combination of genotype data shows that individuals with many risk alleles have a higher diabetes risk than individuals with fewer risk alleles, and genetic tests lead to a statistically significant improvement of prediction models based on simple anthropometric and clinical data only, this difference is currently not clinically relevant. The novel genetic data substantiate the hypothesis that a genetically programmed beta-cell dysfunction interacts with insulin resistance, caused by environmental and lifestyle factors, in the development of type 2 diabetes. Initial studies indicate that the genetic risk can be modified by lifestyle intervention and that gene variants can have an impact on the therapeutic efficacy of certain drugs. A better understanding of the genetics will result in a deeper insight into the molecular pathogenesis of type 2 diabetes and in the development of novel therapeutic approaches.

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  1. Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum, Leibniz-Zentrum für Diabetesforschung an der Heinrich-Heine-Universität Düsseldorf, Auf’m Hennekamp 65, 40225, Düsseldorf, Deutschland

    C. Herder M.Sc.

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Correspondence to C. Herder M.Sc..

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Herder, C. Genetische Studien zum Typ-2-Diabetes. Diabetologe 6, 203–209 (2010). https://doi.org/10.1007/s11428-009-0500-3

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