1 / 15

Thomas Mandrup-Poulsen, MD, DMSc Professor in Medical Research Methodology

Forårsmøde, Dansk Selskab for Intern Medicin 07.03.08 Frontiers of Internal Medicine. Type 2 diabetes- en inflammatorisk sygdom?. Thomas Mandrup-Poulsen, MD, DMSc Professor in Medical Research Methodology Core Unit for Medical Research Methodology Institute for Biomedical Sciences

adeola
Télécharger la présentation

Thomas Mandrup-Poulsen, MD, DMSc Professor in Medical Research Methodology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Forårsmøde, Dansk Selskab for Intern Medicin 07.03.08 Frontiers of Internal Medicine Type 2 diabetes- en inflammatorisk sygdom? Thomas Mandrup-Poulsen, MD, DMSc Professor in Medical Research Methodology Core Unit for Medical Research Methodology Institute for Biomedical Sciences University of Copenhagen Research Director Department for Translational Diabetology Steno Diabetes Center

  2. Etio-pathogenesis of Type 2 Diabetes Genetic susceptibility Obesity Inflammation b-cell dysfunction/apoptosis Insulin resistance + Type 2 diabetes

  3. Adipokine expression and secretion by adipose tissue in lean subjects Bastard J-P Eur Cytokine Netw 2006; 17: 4-12

  4. Adipokine expression and secretion by adipose tissue in insulin-resistant, obese subjects Bastard J-P Eur Cytokine Netw 2006; 17: 4-12

  5. Model of integration of inflammatory and metabolic pathways that interfere with insulin action Hotamisligil GS Diabetes 2005; Suppl.2: S73-78

  6. Low-grade elevated systemic levels of CRP and IL-6 in Type 2 diabetes CRP IL-6 Kolb H, Mandrup-Poulsen T. Diabetologia 2005; 48: 1038-50

  7. Intervention studies on surrogate end-points Drug Acronym Surrogate Ref Pravastatin PRINCE CRP indep. of LDL 1 Pravastatin CARE CRP ” 2 Glitazones CRP, leptin, PAI-1, TNFa 3 Aspirin BG 3, 4 NSAID BG 5 Anti TNF, short term Insulin sensitivity, no effect 6-9 1 Albert MA et al JAMA 2001; 286: 64-70 2 Ridker PM et al Circulation 1999; 100: 230-5 3 Dandona P et al JCEM 2003; 88: 2422-9 4 Ebstein W. Berlin Klin Wochenschrift 1876; 13: 337 5 Robertson RP Diabetes 1983; 32: 231-4 6 Ofei F et al Diabetes 1996; 45: 881-5 7 Paquot N et al JCEM 2000; 85: 1316-19 8 Di Rocco P et al Obes Res 2004; 12: 734-9 9 Dominguez H et al J Vasc Res 2005; 42: 517-25

  8. Etio-pathogenesis of Type 2 Diabetes Inflammation b-cell dysfunction/apoptosis

  9. Islet inflammation and IL-1 in Type 2 diabetes • IL-1 causes functional inhibition and apoptosis of b-cells1 • Macrophage infiltration in islets of Type 2 diabetic animals and patients2 • Glucose-induced human b-cell apoptosis prevented by IL-1Ra3 • b-cells express IL-1 mRNA in Type 2 diabetic patients4 1 Mandrup-Poulsen T et al Diabetologia 1986; 29: 63‑67 2 Ehses J et al Diabetes 2007; 56: 2356-70 3 Maedler K et al J Clin Invest 2002,110;851-60 4 Boni-Schnetzler M et al ADA 2007 Diabetes 2007 (suppl. 1)

  10. Larsen CM et al N Engl J Med 2007; 356; 1517-26

  11. Larsen CM et al N Engl J Med 2007; 356; 1517-26

  12. Larsen CM et al N Engl J Med 2007; 356; 1517-26

  13. Conclusions • This study provides proof-of-principle that IL-1 is an important mediator of impaired glycemia in Type 2 diabetes by affecting b-cell function • The results suggest that long-term inhibition of IL-1 action may preserve b-cell function in Type 2 diabetic patients

  14. Investigators The Steno Team The Zürich Team Modelling and biostatistics

More Related