Diabetes

Question 1

What is MODY?

Answer 1

Maturity onset diabetes of the young - autosomal dominant condition.

Question 2

What is the most common type of MODY?

Answer 2

HNF-1a (hepatic nuclear factor).

Puts a hold on production of islet transcription factors for enzymes and regulation of insulin release - therefore no insulin release.

Question 3

What are the other causes of MODY?

Answer 3

Glucokinase absence/abnormality
HNF-4a
HNF-1b
Neonatal - deficiency of ATP sensitive K+ channel.

Question 4

What is the first line treatment for type 2 diabetes mellitus?

Answer 4

Metformin - a biguanide.

Question 5

What is metformin’s mechanism of action?

Answer 5

Thought to decrease gluconeogenesis by blocking PEPCK (allows pyruvate to bypass PK to form glucose) and G6Pase (G6P to glucose).

Also increases insulin sensitivity by increasing glucose uptake and stimulating glycolysis.

Question 6

What is a potential side effect of metformin?

Answer 6

GI side effects - generally well tolerated if dose is slowly increased.

Question 7

Give 2 examples of sulphonylureas.

Answer 7

Gliclazide and glibenclamide.

Question 8

What is the mechanism of action of sulphonylureas?

Answer 8

Inhibit ATP sensitive K+ channels in B cells to promote insulin release.

Question 9

What are potential side effects of sulphonylureas?

Answer 9

Weight gain and hypoglycaemia.

Question 10

Give an example of a thiazolidinedione.

Answer 10

Pioglitazone.

Question 11

What is the mechanism of action of pioglitazone?

Answer 11

It is a ligand to PPAR-y which stops inappropriate deposition of lipids in non-adipose tissue - essentially causes fat redistribution.

Question 12

What are potential side effects of pioglitzone?

Answer 12

Weight gain
Fluid retention
Increased risk of HF

Question 13

Give 3 examples of DDP-4 inhibitors.

Answer 13

Saxagliptin
Sitagliptin
Vildagliptin

Question 14

What is the mechanism of action of DDP-4 inhibitors?

Answer 14

Prevent the breakdown of GLP-1 and GIP.

Question 15

What are potential side effects of DDP-4 inhibitors?

Answer 15

Nausea.

Question 16

Give 2 examples of GLP-1 receptor agonists.

Answer 16

Exenatide

Liraglutide

Question 17

What is the mechanism of action of GLP-1 receptor agonists?

Answer 17

Physiologically the same as GLP-1, however resist breakdown by DDP-4.

Question 18

What are potential side effects of GLP-1 agonists?

Answer 18

Nausea

Acute pancreatits

Question 19

Give 3 examples of SGLT2 inhibitors.

Answer 19

Canaglifozin
Dapaglifozin
Empaglifozin

Question 20

What is the mechanism of action of SGLT2 inhibitors?

Answer 20

Block SGLT2 channels in the proximal kidney, stopping 25% of glucose being reabsorbed.

Question 21

What are potential side effects of SGLT2 inhibitors?

Answer 21

Increase UTIs and fungi genital infections.
Dehydration if also vomiting/diarrhoea (water moves with glucose)
Ketoacidosis if not on established insulin therapy.

Question 22

What occurs in the early stages of retinopathy?

Answer 22

Non-proliferative.

Hyperglycaemia damages the vessel wall, forming microaneurysms. If these rupture then dot haemorrhages and micro infarcts form.

When blood drains away, protein and fluid remain - hard exudates.

Question 23

What occurs in the later stages of retinopathy?

Answer 23

Proliferative.

Veins are damaged causing venous budding and blockage of the blood supply, causing ischamia.

Ischaemia causes VEGF and GFs to be released which cause neovascularisation (proliferative retinopathy). These vessels are fragile and are prone to bursting.

If they burst can cause a vitreous haemorrhage.

Question 24

What is the progressive of nephropathy?

Answer 24

• Renal enlargement and hyperfiltration.
• This causes glomerular damage (thickened bm, capillary damage)
• This leads to microalbuminuria
• Then macroalbuminuria
• Then eventually may lead to end stage kidney disease.

Question 25

What symptoms occur in peripheral neuropathy?

Answer 25

Numbness Pain Unusual sensitivity/tenderness when feet are touched Decreased vibratory sensation then pressure sensation Reflexes go with progression

Question 26

What is diabetic foot?

Answer 26

Neuropathy and peripheral vascular disease leading to infection, ulcers and ischaemia.

Question 27

What is charcot's foot?

Answer 27

A medical emergency - dysregulated blood flow with increased bone turnover. This leads to fragile bones. Neuropathy means there is repetitive microtrauma to the foot, leading to stress fractures.

Question 28

What effects can autonomic neuropathy have on the CV system?

Answer 28

Vagal neuropathy - tachycardia Loss of sympathetic tone to peripheral arterioles - postural hypotension

Question 29

What effects can autonomic neuropathy have on the GI system?

Answer 29

Vagal neuropathy - gastroparesis Damage to parotid gland - gustatory sweating - forehead, face, scalp and neck after ingesting food.

Question 30

What effects can autonomic neuropathy have on the GU system?

Answer 30

Erectile dysfunction - due to atherosclerosis and nerve damage. Bladder - loss of tone, incomplete emptying

Question 31

What is diabetic amyotrophy?

Answer 31

Painful proximal neuropathy, usually on the buttock or thigh.

Question 32

What is mononeuritis multiplex?

Answer 32

Painful, asymmetric motor and sensory neuropathy affecting two or more nerves.

Question 33

How can retinopathy be treated?

Answer 33

Laser VEGF inhibitors (stop proliferative retinopathy) Vitrectomy

Question 34

How can neuropathy be managed?

Answer 34

If microalbuminuria - | ACE inhibitor or Ang II receptor blocker to prevent profession to macroalbuminuria