1. Obesity & Inflammation: Relationships to Type 2 Diabetes and CVD Hannah Coakley January 10 th, 2014

2. Obesity & Inflammation: a Delicate Balance

3. The Adipocyte: An Endocrine Entity

4. The Overlapping Work of the Adipocyte and the Macrophage

5. JNK/IKK: Pro-Inflammatory Insulin Inhibitors (the Grandaddies of TNF & IL-6)

6. The Inflammatory Troublemakers: TNF-alpha and IL-6 TNF-alpha -- is an adipokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase immune reaction (fever, cell death, inflammation) IL-6 – pro-inflammatory cytokine and myokine, secreted from both smooth muscle cells and macrophages

7. Inflammatory Signaling and Insulin Resistance: An Overview

8. What’s Blood Got To Do (Got To Do) With It?

9. Tying It All Together, Part 1… http://www.youtube.com/watch?v=fwlLddvcBsc

10. Tying It All Together, Part 2…

11. Where Do We Fit In? Everywhere! There is no clear evidence on the direction of causality – does Type 2 Diabetes directly exacerbate CVD or does the general pro- inflammatory environment cause both? Does inflammation cause insulin resistance or vice versa?

12. However, What IS clear is that patients who have decreased their A1c (even by 1%) have better long-term cardiovascular outcomes than those whose elevated A1cs remain unchanged. ANY steps towards decreasing inflammation (through overall weight loss, lipid management, glucose management or decreased blood pressure) will result in better overall heart health outcomes

13. References 1) The Art and Science of Diabetes Self-Management Education Desk Reference, 2 nd Edition, Chapter 24 2) Does Inflammation Trigger Insulin Resistance and Diabetes?, Scientific American, 12/16/2009 3) Elmquist, Joel et al. Neuroendocrine and Endocrine Pathways of Obeisty. JAMA. 2012 4) Wellen, Kathryn et al. Inflammation, stress, and diabetes. Journal of Clinical Investigation. 2005 5) American Journal of Physiology: Endocrinology and Metabolism (figure credit) 6) The National Diabetes Center. diabetesmellitus.org (figure credit)