Endocrine 2 (Type 2 Diabetes | Cardio Risk ) Flashcards
What is Type 2 Diabetes
Insulin Resistance
Hyperinsulinemia
Hyperglycemia
- Later stages beta-cell destruction
Type 1 vs Type 2 Diabetes
Type 1 can be treated with insulin therapy
Type 2 can only be treated with insulin therapy at later stages
Methods to lower glucose in Type 2 Diabetes
Overcome Insulin Resistance
Insulin Independent Methods of Glucose-Lowering
Overcome Insulin Resistance
- Methods?
- Insulin Secretagogues
- Thiazolidinedione
- Metformin?
Insulin Independent Methods of Glucose-Lowering
- Methods?
Decrease Hepatic Glucose Production
- Metformin
Prevent Dietary Glucose Absorption
- Alpha-Glucosidase Inhibitors
Secretagogues
- Examples
1st Generation Sulfonylureas
- Tolbutamide, Chlorpropamide, Acetohexamide
2nd Generation Sulfonylureas
- Glyburide, Glipizide, Glimepiride
Secretagogues
- 1st vs 2nd Generation
2nd Generation Sulfonylureas:
- More potent
- Shorter half life
- Fewer side effects
Less dose needed to get insulin secretion
Secretagogues
- MOA
- Sulfonylurea binds the sulfonylurea receptor/subunit of the K(ATP) channel
- Inhibits K(ATP) channel
- Prevents K+ efflux causing depolarization
- Activates Ca2+ channels causing Ca2+ influx
- Exocytosis of insulin from insulin granules
Result: Increased Insulin Secretion to overcome Insulin resistance
Secretagogues
- Adverse Effects
- Hypoglycemia
- Weight Gain
- Cardiovascular Complications (KATP channels are important in preventing ischemic events)
Non-Sulfonylurea Secretagogues
- Example
- Repaglinide
- Nateglinide
Non-Sulfonylurea Secretagogues
- MOA
- Binds to a different site on K(ATP) Channel
- Inhibits K(ATP) channel
- Prevents K+ efflux causing depolarization
- Activates Ca2+ channels causing Ca2+ influx
- Exocytosis of insulin from insulin granules
More selective for beta cell K(ATP) channels than cardiac cell K(ATP) channels
Rapid onset and Short duration
- Lower risk of hypoglycemia
Alpha-Glucosidase Inhibitors
- Examples
- Acarbose
- Miglitol
- Voglibose
Alpha-Glucosidase Inhibitors
- MOA
- Competitive inhibitor of intestinal alpha-glucosidase enzyme.
- Preventing the breakdown disaccharides
- Delays/Decreases absorption of monosaccharides
- Reduces postprandial glucose rise
Result: Preventing dietary glucose absorption, thus, lowering glucose
Alpha-Glucosidase Inhibitors
- Adverse Effects
- Least effective oral antidiabetic drug
- Does not influence insulin = No Hypoglycemia
- Unbroken sugars cause issues GI issues
Thiazolidinediones
- Examples
Rosiglitazone, Pioglitazone, Troglitazone
Thiazolidinediones
- MOA
Insulin Sensitizer
1. Peroxisome Proliferator Activated Receptor Gamma Agonist (PPAR Gamma)
- Nuclear Receptor in Adipose Tissue
2. Manages gene expression to promote uptake and storage of fatty acids into adipose tissue
3. Improves muscle insulin sensitivity as excess fat is not stored in organs
Takes 6-12 Weeks to reach full effect
Thiazolidinediones
- Adverse Effects
- Weight Gain
- Cardiovascular (Rosiglitazone does not actually increase risk of heart attacks, however, its reputation is already ruined)
- Cancer
Biguanides
- Examples
Metformin
Biguanides
- MOA
First Line Therapy
- Increases AMPK, an important regulator in energy metabolism
- Inhibits Glucagon Signaling in Liver
- Decreases hepatic gluconeogenesis
- Promotes glucose uptake skeletal muscle
Biguanides
- AMPK
- Metformin increases AMPK
- AMPK inhibits Acetyl CoA Carboxylase (ACC)
- Increased fatty acid oxidation (Breakdown of Fat)
- Decreased Hepatic Glucose Production
(Less Fatty Liver = Less Glucose Production)
Result: Lower Blood Glucose Levels
Biguanides
- Glucagon
- Metformin inhibits Glucagon signaling
- Prevents Glucagon from activating Hepatic Gluconeogenesis
- Decreased Hepatic Glucose Production
Result: Lower Blood Glucose Levels
Biguanides
- Adverse Effects
- Independent from Insulin = No Hypoglycemia
- GI Symptoms
- Lactic Acidosis (Phenformin)
–> Build up of lactic acid does acidifies the blood
