Treatment of Type II Diabetes

Question 1

What are some chronic implications that can arise from constant hyperglycaemia?

Answer 1

1. Atherosclerosis
2. Renal failure
3. Blindness

Question 2

What are the differences between type I and type II diabetes?

Answer 2

Type 1:

• B cells are completely destroyed
• Insulin dependent
• Detected <30years old (juvenile onset)

Type 2:

• Lack of insulin production & insulin resistance
• Non-insulin dependent
• Detected >40 years old (maturity onset)
• Leads to type 1 diabetes

Question 3

What tests can be performed to check for diabetes?

Answer 3

1. Fasting plasma glucose test
2. Oral glucose tolerance test (OGTT)
3. Random plasma glucose test

Question 4

What levels during a fasting, or random test indicate hyperglycaemia?

Answer 4

Fasting = >7mmol/L

Random on 2 occasions = >11.1mmol/L

Question 5

What should normal HbA1C levels be?

Answer 5

<7% (or <48mmol/mol)

Question 6

How can diabetic ketoacidosis (DKA) occur?

Answer 6

Fats in the liver are broken down into fatty acids, which are converted to ketones which make the blood acidic.

Question 7

What is one major risk factor for type 2 diabetes?

Answer 7

Obesity

Question 8

What are the classes of drugs used to treat type 2 diabetes?

Answer 8

1. Biguanides
2. Sulfonylureas
3. Thiazolidinediones
4. DPP4 inhibitors
5. SGLT-2 inhibitors
6. GLP-1 agonists

Question 9

How do sulfonylureas (e.g. gliclazide, or glipizide) work?

Answer 9

They block K+ channels, which depolarises B cells and opens Ca2+ channels to allow insulin release.

Question 10

How do biguanides (e.g. metformin) work?

Answer 10

1. Metformin enters the cell via OCT 1
2. It then increases the conc. of AMP, activating AMPK
3. AMPK then increases glucose uptake/glycogenesis and decreases gluconeogenesis/glycogenolysis

• This all leads to a lower BG level

Question 11

How does exercise lead to lower BG levels, on a cellular level?

Answer 11

Exercise involves muscle contraction which generates AMP = activating AMPK
AMPK promotes glucose to bind to GLUT 4 receptors on cells to and lower BG levels

Question 12

How do thiazolidinediones (e.g. pioglitazone) work?

Answer 12

They modulate gene transcription of glucose metabolism.

Expression of enzymes which break down glucose is enhanced.

Question 13

How do DPP4 inhibitors (e.g. linagliptin, or sitagliptin) work?

Answer 13

They delay GLP-1 inactivation, which increases insulin secretion after meals and decreases glucagon release.