Inflammation and Type 2 Diabetes: Results from KORA Augsburg

Zusammenfassung

Typ-2-Diabetes ist mit einer subklinischen systemischen Entzündung verbunden. Erhöhte systemische Spiegel an Glykoproteinen und Akutphaseproteinen sowie erhöhte Leukozytenzahlen in Patienten mit Typ-2-Diabetes wurden bereits in den 1960er-Jahren in Querschnittsstudien nachgewiesen. Später zeigten prospektive Studien, dass erhöhte Spiegel verschiedener Akutphaseproteine und Zytokine prädiktiv für die Entwicklung eines Typ-2-Diabetes sind. Immungenvarianten modulieren im Tiermodell und im Menschen Insulinresistenz und Diabetesinzidenz und die Therapie des Typ-2-Diabetes mit Pharmaka, Ernährung oder körperlicher Bewegung reduziert signifikant die systemische Konzentration verschiedener Immunmediatoren. Immunologische Untersuchungen im Rahmen des KORA-Surveys S4 (1999/2001) belegten, dass die Konzentrationen von zirkulierenden Akutphaseproteinen wie CRP stark mit den Serumspiegeln von IL-6 korrelieren und nicht nur bei manifestem Typ-2-Diabetes, sondern bereits im Stadium der gestörten Glukosetoleranz erhöht sind. Dies deutet darauf hin, dass diese Mediatoren in die Pathogenese des Typ-2-Diabetes involviert sind. TNFα hingegen war weder mit CRP koreguliert, noch mit dem Diabetesstatus assoziiert. Unsere Ergebnisse zeigen daher, dass Typ-2-Diabetes von einer nicht-zufälligen und differenziell regulierten Aktivierung der natürlichen Immunität begleitet wird, und implizieren, dass dieser Entzündungsstatus mit der Entstehung der Erkrankung in engem Zusammenhang steht. Weitere Arbeiten werden das Spektrum der Untersuchungen auf Chemokine ausdehnen und die Assoziation der Immunmarker mit Adipositas prüfen, um zu klären, ob dieser klassische Diabetes-Risikofaktor relevant für die Entstehung der subklinischen Entzündung ist.

Abstract

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFα was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.

Diabetes - gestörte Glukosetoleranz - Entzündung - Interleukin-6 - natürliche Immunität

Diabetes - impaired glucose tolerance - inflammation - interleukin-6 - innate immunity

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