Diabetes Flashcards
How is glucose regulated?
2 hormones:
1. Insulin - decrease blood glucose levels
2. Glucagon - increase blood glucose levels
What is diabetes?
Diabetes Mellitus is a group of metabolic diseases
High blood glucose = hyperglycemia
What are the 2 main subtypes of diabetes?
Type 1: immune-mediated, juvenile-onset. 5-10% of all cases
Type 2: non-insulin-dependent, adult-onset. 90-95% of all cases
What is Type 1 Diabetes?
Autoimmune disease:
Impaired insulin production by beta cells due to its destruction by T-cells (hyperreactive response)
What causes Type 1 Diabetes?
Unknown
Likely due to genetics, environment (viral infection)
What are symptoms of Type 1 Diabetes?
Polyuria (urinate often), polyphagia (extreme hunger), polydipsia (extreme thirst)
Ketoacidosis
What causes diabetic ketoacidosis?
Not enough insulin -> liver breaks down fat to fatty acids (lipolysis) -> release ketone bodies -> energy, increase blood acidity
What are 2 serious conditions resulting from ketoacidosis?
- Kussmaul breathing (deep, laboured)
- Hyperkalemia (high blood K+)
How is Type 1 Diabetes treated?
Bolus/basal insulin injection (subcutaneous)
Bolus Insulin Injection: When is it used, example
Used following a meal
Short acting: Insulin regular
Basal Insulin Injection: When is it used, example
Used during periods of fasting, between meals/overnight
Long acting: Insulin glargine
What is Type 2 Diabetes?
Adult onset disease:
Cells not able to adequately respond to insulin (beta cell failure), insulin resistance
What causes Type 2 diabetes?
- Lifestyle
- Genetics
What are symptoms of Type 2 diabetes?
Polyuria (incd. urination), polyphagia (incd. hunger), polydipsia (incd. thirst), Hyperosmolar hyperglycemic state (HHS) - high blood glucose levels
What is hyperosmolar hyperglycemic state (HHS)?
Complication where high blood glucose levels -> increased plasma osmolarity
More water taken in -> increased urination -> total body dehydration
How is Type 2 Diabetes treated?
Lifestyle change
Pharmacological management
What classes of drugs are used to treat diabetes? (6)
- Biguanide
- Sulfonylurea
- Alpha-glucosidase Inhibitors
- GLP-1 Receptor Agonists
- DPP-4 Inhibitors
- SGLT2 Inhibitors
Biguanide: MOA
- Inhibit mitochondrial Complex I->decrease hepatic gluconeogenesis
- Increase tyrosine kinase activity->increase insulin sensitivity
- Increase GLUT4 glucose transporter activity->increase glucose uptake by skeletal cells
- Increase glucose metabolism in enterocytes-> reduced net glucose uptake across intestinal wall
Biguanide: Example, Side effects
Example: Metformin (oral) -> Type 2 Diabetes
Side effects: Gastrointestinal irritation, lactic acidosis (rare, at risk for patients with compromised kidney function)
Sulfonylurea: MOA
- Bind ATP sensitive K+ channel
- Channel closes, prevent K+ from leaving -> K+ buildup
- Depolarization of beta cell membrane
- Ca2+ channels open -> Ca2+ influx
- High Ca2+ conc. -> insulin vesicles migrate to beta cell membrane
- Insulin vesicles fuse to membrane -> insulin exocytosed (released)
Sulfonylurea (example, side effects)
Example: glyburide
Side effects: Hypoglycemia, weight gain
Alpha-glucosidase inhibitors: MOA
Inhibits alpha-glucosidase activity
Glucosidase: on brush border of small intestine, breaks down starch/disaccharide -> glucose -> facilitate absorption through intestinal wall
Alpha-glucosidase inhibitors: Example, side effects
Example: Acarbose (oral)
Side effects: gastrointestinal (abdominal/stomach pain, flatulence, diarrhea)
SGLT2 Inhibitors: MOA
Inhibit sodium-glucose transport protein (SGLT)
SGLT: reabsorbs glucose from kidney (renal glucose resorption)
SGLT2 Inhibitors: Example, side effects
Example: Canagliflozin (oral)
Side effects: Increased urinary tract infection, urination, risk of ketoacidosis
GLP-1 Receptor Agonists: MOA
- Incretin mimetic, binds GLP-1 receptor of pancreatic beta cells
- Elevates levels of cytosolic Ca2+ -> increases exocytosis of insulin-containing granules
GLP-1 Receptor Agonist: Example, side effects
Example: Ozempic (subcutaneous)
Side effects: gastrointestinal, acute prancreatitis, hypoglycemia risk, stomach paralysis, weight loss
DPP4 inhibitors: MOA
Block Dipeptidyl peptidase-4 (DPP-4) -> increase incretin levels -> increase insulin secretion, inhibit glucagon release
DPP-4: Transmembrane glycoprotein that degrades incretins (eg. GLP-1, faciliates insulin secretion)
DPP-4 Inhibitors: Example, side effects
Example: Sitagliptin (oral)
Side effects: Headaches, leg welling, upper respiratory tract infections, hypoglycemia, pancreatitis, joint pain
