Diabetes Therapies

Question 1

What to aim for when treating Type 2 diabetes?

Answer 1

10-15% reduction in weight to BMI of 20-25

Question 2

Why is oral hyperglycaemic therapy required?

Answer 2

Regulate blood glucose

Question 3

How much ATP from one molecule of glucose?

Answer 3

Glycolysis = 2
Citric Acid = 2
Electron Transfer = 26
» Total = 30 ATP

Question 4

How does insulin act on glucose levels?

Answer 4

1. Insulin binds to the insulin receptor
2. Receptor is phosphorylated
3. Activates the cell signalling
4. Releases GLUT4
5. GLUT4 imports glucose therefore loweing BG

Question 5

What does the insulin structure consist of?

Answer 5

Two peptide chains linked by two disulfide bonds

Question 6

What is the 2 phase release from beta cells?

Answer 6

1st phase - rapid release of stored insulin
2nd phase - slow release following synthesis

Question 7

What is the half life of endogenous insulin?

Answer 7

3-5 minutes

Question 8

How does zinc affect insulin preparations?

Answer 8

• Increases stability of insulin
• Delays site absorption

Question 9

What are the 4 classes of injectable insulins?

Answer 9

• Rapid acting (5-15 min onset)
• Short acting (peak 2-3hr)
• Intermediate (peak 6-12hr)
• Long-acting (10-24hr)

Question 10

What are the undesirable effects of insulin?

Answer 10

• Hypoglycaemia (brain damage/cardiac arrest)
• DKA
• Insulin allergy
• Lipdystrophy (animal insulin)

Question 11

How is insulin release controlled?

Answer 11

SUR1/potassium pump

Question 12

What alters the monomer/hexamer formation?

Answer 12

Amino acid modification

Question 13

What are the 3 strategies to lower blood glucose?

Answer 13

• Increase cellular sensitivity to insulin
• Increase insulin release
• Reduce/delay glucose absorption into the blood

Question 14

How is metformin eliminated?

Answer 14

100% renally eliminated, NOT metabolised

Question 15

What is the plasma half-life of metformin?

Answer 15

1-5hrs

Question 16

What does pioglitazone bind to?

Answer 16

Receptor in the nucleus called peroxisome proliferator-activated receptor (PPAR)

Question 17

What does altering the gene transcription lead to?

Answer 17

• Insulin sensitisation
• Increased glucose uptake in the cells

Question 18

How does pioglitazone impact cytokines ?

Answer 18

• Decreases IL-6 (- regulator of insulin receptor)
• Increases adiponectin (+ regulator of insulin receptor)

Question 19

What drugs may impact Thiazolidinedione levels?

Answer 19

Drugs effecting CYP3A4

Question 20

What are the effects of Thiazolidinediones?

Answer 20

• Weight gain
• Liver dysfunction (rare)
• Fluid retention (kidneys)

Question 21

How do GLP mimetics work?

Answer 21

Increase insulin, lowers glucagon, lowers BG
Excreted by kidneys so not approved for patients with a eGFR <30ml/min

Question 22

What is the role of SGLT2?

Answer 22

Glucose reabsorption

Question 23

What are glifozins?

Answer 23

Competitive reversible inhibitors of SGLT2

Question 24

What are the drugs of the following 3 stratergies?
1. Increase cellular sensitivity to insulin
2. Increase insulin release
3. Alter glucose absorption

Answer 24

1. Metformin (alter gluconeogenesis)
   Thiazolidinediones (increase GLUT & insulin receptor genes)
2. Sulphonylurease (block Sur1 to increase insulin release
   Intecrin activation (following digestion)
   GLP-1 agonists (activate)
   DPP4 inhibitors (prevent GLP-1 breakdown)
3. SGLT2 inhibitors (block kidney transporter so glucose is urinated out)