Understanding the Link between Understanding the Link between Diabetes and Obesity… Diabetes and Obesity…
and What You Can Do About it!and What You Can Do About it!
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: [email protected]
February 16, 2012 - Gainesville, Florida
DIABETESDIABETES 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.
K Cusi. Current Diabetes Reports. 2010 Aug;10(4):306-15
What is Pre-DiabetesWhat 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.
Risk Factors for DiabetesRisk 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
Hemoglobin Hemoglobin A-1-CA-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.
Things to do to better to Things to do to better to manage your diabetesmanage 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
GOOD DIABETES CAREGOOD 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
Objetive for the Objetive for the “Keep on track” booklet“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
Remember to take care of your Remember to take care of your diabetes by: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.
Molecularmechanismsof lipotoxicity
• ER stress• Inflammatory
response( JNK, NF-)
• Mitochondrial function
• Insulin resistance
FFA
Lipotoxicity
− HGP− NAFLD− NASH
− insulin-mediated− glucose uptake
−-cell apoptosis− insulin secretion− T2DM
− Cardiac function (CHF?)− Risk of ischemia (?)
− Endothelial dysfunction− Pro-atherogenic damage
atherosclerosis
Healthy AdiposeTissue
Hypertrophic DysfunctionalAdipose Tissue
HypoxiaER stress
JNK
NF-Kb
Lipolysis
Necrosis
HypertropyAdipose tissue
insulinresistance
Adiponectin
Systemic effects
?• Genetic• Early life nutritional insults• Chronic over-feeding
Adipokines
Systemic effects
Adipocyte-macrophagecross-talk
Adiposetissue
infiltration
Macrophage cytokines (TNFa, IL-6, CRP, others)
Macrophage“activation”
K Cusi. Current Diabetes Reports. August 2010, 10:306-315
Diagnosis NAFLD & NASHDiagnosis 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
Imaging: Ultrasound (echogenicity): 65-80% sensitivity for NAFLD
Magnetic ResonanceImaging
Abdominal fat:Visceral and subcutaneous
Liver and Muscle fat
Cardiovascular Disease in NAFLDCardiovascular Disease in NAFLD
0%
20%
40%
60%
80%
CHD CVA PVD All CVD
Without NAFLD NAFLD
Targher G. Diabetes Care 2007;30, 1212-1218N = 2,392
* P < 0.001
**
*
*
??
NEJM 2006, 355, 2297-2307
Mechanism of Action of Thiazolidinediones
TZDinsulin sensitvity lipid storage
Muscle
Muscle
Pancreatic-cellsLiver
FFA and adipocytokines adiponectin
Adipose tissue
???
Directeffects?
K Cusi. New pharmacological approaches in type 2 diabetes mellitus. Edit. Serrano Rios & Gutierrez, Elsevier 2009
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)
0 (normal)
Before treatment biopsy
After treatment biopsy
Effect of PioglitazoneEffect of Pioglitazonein NASHin NASH
Cusi K. In Expert Review of Gastroenterology & Hepatology, 2009
Adverse Effects of TZDsAdverse Effects of TZDs
Weight gain
Water retention, CHF, CVD?
Bone loss? (females)
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
Studies of Pioglitazone in Patients with Studies of Pioglitazone in Patients with NASH (by Kenneth Cusi, M.D. and team)NASH (by Kenneth Cusi, M.D. and team)
FOR MORE INFORMATIONFOR MORE INFORMATION
Contact the
American Diabetes Association at:1-800-DIABETES (342-2383) o online at:
www.diabetes.org
Locally call: 210-829-1765
Take care of your risk Take care of your risk factors!factors!