Diabetes

Question 1

Define T1DM?

Answer 1

Autoimmune destruction of B-cells = insulin deficiency leading to:

1. Hyperglycaemia
2. Ketonaemia

Question 2

Define T2DM?

Answer 2

Based on genetic and environmental factors it is:

1. Abnormal insulin production
2. Impaired insulin action (resistance) from muscle/liver/adipose tissue

Question 3

Describe how metformin works and name four side-effects?

Answer 3

Inhibits hepatic gluconeogenesis (50% of endogenous insulin acts on the liver) - causes weight loss

• Diarrhoea and increased flatulence and nausea
• C/I if GFR<30 due to lactic acidosis

Question 4

Describe how sulphonylureas work, give three examples and name two side-effects?

Answer 4

Insulin secretagogues - bind to Su receptors on the B-cell and this opens K+ channels and depolarises the cell membrane leading to the release of insulin

1. Gliclazide
2. Gliterpirimide
3. Tolbutamide
   - Weight gain and hypoglycaemia

Question 5

Describe how thiazolodinediones work and name three side-effects?

Answer 5

PPAR-Y agonists

1. Enhance lipogenesis
2. Decrease lipolysis
3. Decrease plasma FFA
   - weight gain and increased fracture risk and bladder cancer

Question 6

Describe how incretins work?

Answer 6

Hormones secreted bu intestinal endocrine cells in response to food:
1. Enhance glucose-dependent insulin release (from remaining B-cells)
2. Works on a-cells to suppress glucagon secretion
3. Works on the liver to decrease hepatic glucose output
4. Works on the stomach to decrease the rate of gastric emptying (early satiety)
= Weight loss and NO hypoglycaemia

Question 7

Give two examples of incretins and describe why they need to be given with adjunct treatment?

Answer 7

GLP-1
GIP
Have a short half-life because they are broken down by DDP-IV - therefore need to be given with DDP-IV inhibitors (sitagliptin)

Question 8

Describe how SGLT2 inhibitors work and name two side-effects?

Answer 8

Prevent renal glucose reabsorption vis inhibiting SGLT-1 in the proximal tubule - weight loss
- Increased UTI risk and increased thrush risk due to increased peeing of sugars

Question 9

Give two examples of rapid acting and long-acting insulins respectively?

Answer 9

Rapid acting = Humalog and Novorapid

Long-acting = Glagine amd Detemir

Question 10

Describe the 5 step-wise approach to the treatment of T2DM?

Answer 10

1. Lifestyle
2. Metformin
3. Add sulphonyurea - Gliclazide
4. Add either GLP-1 or SGLT2 inhibitor (triple therapy)
5. Insulin

Question 11

Describe how statins work directly?

Answer 11

Hydroxy-methylglutaryl-CoA reductase inhibitor =
Blocks the 1st step of cholesterol biosynthesis in the liver therefore:
1. Direct reduction of cholesterol (inhibiting biosynthesis)
2. Increased uptake of cholesterol to the liver

Question 12

Describe how statins work in-directly?

Answer 12

1. Improve endothelial functioning
2. Decrease inflammation
3. Plaque stabilisation
   - All of which lead to the inhibition of thrombin formation

Question 13

Name four side-effects stated with statins?

Answer 13

Myositis/myopathy
Rash
GI upset
Sleep disturbance