1. Understanding the Link between Diabetes and Obesity… and What You Can Do About it!
February 16, 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

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

16. Diagnosis NAFLD & NASH Clinical findings: Laboratory: Imaging:
Ultrasound (echogenicity): 65-80% sensitivity for NAFLD
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. Visceral and subcutaneous
Magnetic Resonance
Imaging
Abdominal fat:
Visceral and subcutaneous
Liver and Muscle fat

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

19. ?

22. NEJM 2006, 355,

23. Mechanism of Action of Thiazolidinediones
Adipose tissue
TZD
 insulin sensitvity
 lipid storage ?
 FFA and adipocytokines
 adiponectin ?
Direct
effects? ?
Figure 4. Mechanism of action of thiazolidinediones (TZDs). Reversal of dysfunctional adipose tissue plays a major role in the beneficial metabolic changes mediated by TZDs in obesity and type 2 diabetes mellitus. This involves restoration of adipose tissue insulin sensitivity with reduction of elevated plasma free fatty acid (FFA) levels and of FFA-associated systemic lipotoxicity, as well as a decrease in adipose-derived cytokine production and subclinical inflammation. An increase in plasma adiponectin is also an important feature of TZD therapy. Whether TZDs restore glucose and lipid metabolism in humans also by direct effects on muscle, liver and pancreatic b-cells is under intense investigation.
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 Pioglitazone in NASH
Before treatment biopsy
64 y.o. CF (IGT)
Before
After
BMI (kg/m2)
30.9
32.4
FPG (mg/dl)
109 87
ALT (U/L) 43 17
NASH activity score / Fibrosis 5 2
0 (normal)
After treatment biopsy
Pio D1 (low magn. X 4x objective = 40 x times)
FB 19 and 24
S -3
N/I -2
F 0
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
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. American Diabetes Association at:
FOR MORE INFORMATION
Contact the
American Diabetes Association at:
1-800-DIABETES ( ) o online at:
Locally call:

28. Take care of your risk factors!