Diabetes

Question 1

How is glucose regulated?

Answer 1

2 hormones:
1. Insulin - decrease blood glucose levels
2. Glucagon - increase blood glucose levels

Question 2

What is diabetes?

Answer 2

Diabetes Mellitus is a group of metabolic diseases
High blood glucose = hyperglycemia

Question 3

What are the 2 main subtypes of diabetes?

Answer 3

Type 1: immune-mediated, juvenile-onset. 5-10% of all cases
Type 2: non-insulin-dependent, adult-onset. 90-95% of all cases

Question 4

What is Type 1 Diabetes?

Answer 4

Autoimmune disease:
Impaired insulin production by beta cells due to its destruction by T-cells (hyperreactive response)

Question 5

What causes Type 1 Diabetes?

Answer 5

Unknown
Likely due to genetics, environment (viral infection)

Question 6

What are symptoms of Type 1 Diabetes?

Answer 6

Polyuria (urinate often), polyphagia (extreme hunger), polydipsia (extreme thirst)
Ketoacidosis

Question 7

What causes diabetic ketoacidosis?

Answer 7

Not enough insulin -> liver breaks down fat to fatty acids (lipolysis) -> release ketone bodies -> energy, increase blood acidity

Question 8

What are 2 serious conditions resulting from ketoacidosis?

Answer 8

1. Kussmaul breathing (deep, laboured)
2. Hyperkalemia (high blood K+)

Question 9

How is Type 1 Diabetes treated?

Answer 9

Bolus/basal insulin injection (subcutaneous)

Question 10

Bolus Insulin Injection: When is it used, example

Answer 10

Used following a meal
Short acting: Insulin regular

Question 11

Basal Insulin Injection: When is it used, example

Answer 11

Used during periods of fasting, between meals/overnight
Long acting: Insulin glargine

Question 12

What is Type 2 Diabetes?

Answer 12

Adult onset disease:
Cells not able to adequately respond to insulin (beta cell failure), insulin resistance

Question 13

What causes Type 2 diabetes?

Answer 13

1. Lifestyle
2. Genetics

Question 14

What are symptoms of Type 2 diabetes?

Answer 14

Polyuria (incd. urination), polyphagia (incd. hunger), polydipsia (incd. thirst), Hyperosmolar hyperglycemic state (HHS) - high blood glucose levels

Question 15

What is hyperosmolar hyperglycemic state (HHS)?

Answer 15

Complication where high blood glucose levels -> increased plasma osmolarity
More water taken in -> increased urination -> total body dehydration

Question 16

How is Type 2 Diabetes treated?

Answer 16

Lifestyle change
Pharmacological management

Question 17

What classes of drugs are used to treat diabetes? (6)

Answer 17

1. Biguanide
2. Sulfonylurea
3. Alpha-glucosidase Inhibitors
4. GLP-1 Receptor Agonists
5. DPP-4 Inhibitors
6. SGLT2 Inhibitors

Question 18

Biguanide: MOA

Answer 18

1. Inhibit mitochondrial Complex I->decrease hepatic gluconeogenesis
2. Increase tyrosine kinase activity->increase insulin sensitivity
3. Increase GLUT4 glucose transporter activity->increase glucose uptake by skeletal cells
4. Increase glucose metabolism in enterocytes-> reduced net glucose uptake across intestinal wall

Question 19

Biguanide: Example, Side effects

Answer 19

Example: Metformin (oral) -> Type 2 Diabetes
Side effects: Gastrointestinal irritation, lactic acidosis (rare, at risk for patients with compromised kidney function)

Question 20

Sulfonylurea: MOA

Answer 20

1. Bind ATP sensitive K+ channel
2. Channel closes, prevent K+ from leaving -> K+ buildup
3. Depolarization of beta cell membrane
4. Ca2+ channels open -> Ca2+ influx
5. High Ca2+ conc. -> insulin vesicles migrate to beta cell membrane
6. Insulin vesicles fuse to membrane -> insulin exocytosed (released)

Question 21

Sulfonylurea (example, side effects)

Answer 21

Example: glyburide
Side effects: Hypoglycemia, weight gain

Question 22

Alpha-glucosidase inhibitors: MOA

Answer 22

Inhibits alpha-glucosidase activity
Glucosidase: on brush border of small intestine, breaks down starch/disaccharide -> glucose -> facilitate absorption through intestinal wall

Question 23

Alpha-glucosidase inhibitors: Example, side effects

Answer 23

Example: Acarbose (oral)
Side effects: gastrointestinal (abdominal/stomach pain, flatulence, diarrhea)

Question 24

SGLT2 Inhibitors: MOA

Answer 24

Inhibit sodium-glucose transport protein (SGLT)
SGLT: reabsorbs glucose from kidney (renal glucose resorption)

Question 25

SGLT2 Inhibitors: Example, side effects

Answer 25

Example: Canagliflozin (oral)
Side effects: Increased urinary tract infection, urination, risk of ketoacidosis

Question 26

GLP-1 Receptor Agonists: MOA

Answer 26

1. Incretin mimetic, binds GLP-1 receptor of pancreatic beta cells
2. Elevates levels of cytosolic Ca2+ -> increases exocytosis of insulin-containing granules

Question 27

GLP-1 Receptor Agonist: Example, side effects

Answer 27

Example: Ozempic (subcutaneous)
Side effects: gastrointestinal, acute prancreatitis, hypoglycemia risk, stomach paralysis, weight loss

Question 28

DPP4 inhibitors: MOA

Answer 28

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)

Question 29

DPP-4 Inhibitors: Example, side effects

Answer 29

Example: Sitagliptin (oral)
Side effects: Headaches, leg welling, upper respiratory tract infections, hypoglycemia, pancreatitis, joint pain