1. Treatment of Type 2 Diabetes: Pathophysiology Conclude: do so without Hypoglycemia or Visceral Fat Weight Gain 1

2. Natural History of Type 2 Diabetes- Insulin Resistance
Age
Envir.+ Other Disease
Genes
Macrovascular Complications
Obesity
Poor Diet Inactivity
IR phenotype Atherosclerosis obesity hypertension HDL, TG
Endothelial dysfunction PCO
Disability
Insulin Resistance
MI CVA Amp
IGT Type II DM
DEATH
 Beta Cell Secretion
d.ec 1st phase
Inc 2nd phase
Blindness Amputation CRF
Eye Nerve Kidney
Risk of Dev. Complications
ETOH BP Smoking
Disability
Microvascular Complications 2

4. Greater the Insulin Level, > CV Risk

5. Peripheral Insulin Resistance- Induced Hyperinsulinemia has Adverse Downstream Effects
Metabolic pathway
(PI3K)
Mitogenic pathway
(MAPK)
Proliferation, ENDOTHELIAL DYSFUCTION, INFLAMMATION
Hyperglycemia
Glucose transport
Glykogen synthese

6. Multiple Causes of Insulin Resistance-More Ubiquitous and Multiple Therapies Available
Central IR
Weight Reduction
DM MEDS- SGLT-2 inh.
GLP-1 RAs
Appetite suppressants
Bromocriptine-QR
Hyperinsulinemia
Biome IR
OBESITY-
Peripheral IR
Inflam-
mation IR
Anti-
Inflam.
Incretins
Pro-
Biotics,
Pre-Biotics’
Antibiotics
Pioglitazone
Metformin

7. Implications for Therapy
Understand and Treat Central Mechanisms IR
Understand and Treat Peripheral IR- fat, liver, muscle
Understand and Treat Inflammation
Understand and Treat Biome