Understanding the Link between Diabetes and Obesity… and What You Can Do About it!

1. Understanding the Link between Diabetes and Obesity… and What You Can Do About it! February 16, 2012 - Gainesville, Florida Kenneth Cusi, M.D., F.A.C.P., F.A.C.E. Professor of Medicine Chief, Endocrinology, Diabetes and Metabolism Division University of Florida, Gainesville, USA E-mail: Kenneth.Cusi@medicine.ufl.edu

3. DIABETES • When you eat, your body breaks food down into sugar and sends it into your bloodstream. • Insulin (made in the pancreas) helps get the sugar from the blood into the cells to be used for energy needed for daily life. It’ • Insulin like the key that opens the door for the cells. • Diabetes is when the body does not make enough insulin and/or the insulin it makes does not work well. Too much sugar in the blood usually means that a person has diabetes.

5. K Cusi. Current Diabetes Reports. 2010 Aug;10(4):306-15

6. What is Pre-Diabetes? • Pre-diabetes is when a person has too much sugar in their blood, but not quiet high enough to be called diabetes. (100-125 mg/dl). • People with pre-diabetes: • Can make changes to their eating habits to help them lose weight and increase their physical activity to delay or prevent diabetes. • Eating healthy is for everyone, but it is especially important for managing or preventing diabetes.

7. Risk Factors for Diabetes • You are overweight • You rarely excercise • You are 45 or older • You are Hispanic/Latino • You have high blood pressure (140/90 or higher) • Someone in your family has diabetes • You are a woman who has a history of diabetes during pregnancy or has had a baby weighing more than 9lbs at birth

8. Hemoglobin A-1-C • The A1C tells you your average blood • glucose levels for the past 2 to 3 months. • Think of it as a blood test that “memorizes” your blood sugar level. • Your A1C target should be less than 7%. • The A1C test provides your health care provider with information on how well your diabetes is under control.

9. Things to do to better to manage your diabetes • Take your medication as instructed • Monitor my blood glucose more closely and record results for your health care provider • Develop a plan with your health care provider • Develop a healthy meal plan • Be more active and lose weight

10. GOOD DIABETES CARE • Be physically active everyday • Meal planning, be mindful of what and how much you eat • Take your diabetes medications as prescribed • Check your blood glucose levels. Talk with your healthcare provider about how often you should • Visit your healthcare provider as recommended

11. Objetive for the “Keep on track” booklet • Create awareness of the importance of getting your A1C, blood pressure and cholesterol checked • Take with you to every doctor’s visit to record progress. • Have a list of emergency contacts

12. Remember to take care of your diabetes by: • Using a meal plan and being active • Taking your diabetes medications or insulin • Talking to your healthcare provider if your plan isn’t working or not meeting your goals.

15. Healthy Adipose Tissue Macrophage “activation” Hypertrophic Dysfunctional Adipose Tissue Macrophage cytokines (TNFa, IL-6, CRP, others) Adipose tissue infiltration ? Hypoxia ER stress • Genetic • Early life nutritional insults • Chronic over-feeding Hypertropy JNK Adipose tissue insulin resistance NF-Kb Adipocyte-macrophage cross-talk Necrosis Lipolysis Molecular mechanisms of lipotoxicity Adiponectin Adipokines FFA Lipotoxicity • ER stress • Inflammatory response( JNK, NF-Kb) • Mitochondrial function • Insulin resistance Systemic effects Systemic effects atherosclerosis • b-cell apoptosis • insulin secretion • T2DM • HGP • NAFLD • NASH • insulin-mediated • glucose uptake • Endothelial dysfunction • Pro-atherogenic damage • Cardiac function (CHF?) • Risk of ischemia (?) K Cusi. Current Diabetes Reports. August 2010, 10:306-315

16. Imaging: • Ultrasound (echogenicity): 65-80% sensitivity for NAFLD Diagnosis NAFLD & NASH • Clinical findings: • Few clinical symptoms (i.e., right upper quadrant discomfort) • Requires a high degree of clinical suspicion • Laboratory: • May be associated with elevated liver aminotransferases (ALT>AST) • May NOT be associated with an elevation in ALT/AST

17. Abdominal fat: Visceral and subcutaneous Magnetic Resonance Imaging Liver and Muscle fat

18. * P < 0.001 * Cardiovascular Disease in NAFLD * * * N = 2,392 Targher G. Diabetes Care 2007;30, 1212-1218

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22. NEJM 2006, 355, 2297-2307

23. Adipose tissue TZD  insulin sensitvity lipid storage ?  FFA and adipocytokines  adiponectin ? Direct effects? ? Mechanism of Action of Thiazolidinediones Muscle Pancreatic b-cells Muscle Liver K Cusi. New pharmacological approaches in type 2 diabetes mellitus. Edit. Serrano Rios & Gutierrez, Elsevier 2009

24. Effect of Pioglitazonein NASH Before treatment biopsy After treatment biopsy Cusi K. In Expert Review of Gastroenterology & Hepatology, 2009

25. Adverse Effects of TZDs • Weight gain • Water retention, CHF, CVD? • Bone loss? (females)

26. Studies of Pioglitazone in Patients with NASH (by Kenneth Cusi, M.D. and team) • University of Florida/Shands - NASH study • Screening for patients with fatty liver • Free state-of-the-art metabolic assessments and advice on long-term management • Done by Dr. Cusi and team • VA Gainesville, FL - NASH study • Patients with T2DM • Vitamin E +/- pioglitazone vs. placebo

27. FOR MORE INFORMATION Contact the American DiabetesAssociation at: 1-800-DIABETES (342-2383) o online at: www.diabetes.org Locally call: 210-829-1765

28. Take care of your risk factors!