Poster 2- treatment of diabetes

Question 1

Generalised treatment of type 1 diabetes

Answer 1

Insulin therapy to get glycemic control. Done using a basal bolus regimen

Question 2

Generalised treatment of type 2 diabetes

Answer 2

First start with healthy diet and exercise to lose weight.
Then add oral therapy
Then injection therapy.
Exogenous insulin is the last line of treatment and occurs when all the beta cells have been destroyed.

Question 3

Treatment ladder for type 2 diabetes

Answer 3

Metformin
Metformin + sulphonylurea (consider swapping for a DPP4 inhibitor or TZD if contraindicated)
Add TZD or insulin
Metformin + sulphonylurea + insulin
Increase insulin dose and intensify regime.

Question 4

Metformin is a….. drug

Answer 4

Biguanide

Question 5

Metformin does…. to the body

Answer 5

Reduces hepatic gluconeogenesis (therefore the liver isn’t contributing to raising the blood glucose)
Increases glucose uptake in skeletal muscles
Reduces carbohydrate absorption
Increases oxidation of fatty acids

Question 6

Dosage of metformin

Answer 6

Max- 3g daily

Usually start on 500g OD or BD

Question 7

Positive outcomes for patients on metformin

Answer 7

Reduction in HbA1c of 15-20mmol by lowering insulin resistance
Weight loss
Reduction in bp
No hypos
Prevents microvascular and microvascular complications
Safe in pregnancy

Question 8

Which drugs can metformin be used alongside

Answer 8

Sulphonylureas, glitazones and insulin

Question 9

Examples of sulfonylureas and their doses

Answer 9

Glicazide (40mg OD to 160mg BD)
Glipizide (2.5mg to 15mg)
Glibenclamide

Question 10

How do sulfonylureas work?

Answer 10

They work by binding to the ATP dependent potassium channel closing it. This causes depolarisation of the cell that then leads to calcium channels opening. Calcium influx then stimulates insulin release.

Question 11

Describe the Katp channel

Answer 11

Made up of 4 Kir6 subunits and 4 SUR1 subunits.
Usually the ATP binds to the 4 Kir6 subunits closing the channel.
ADP-Mg binds to the SUR1 channels thus opening the channels.
Sulfonylureas displace the ADP-Mg keeping the channel patent.

Question 12

Positive effects of sulfonylureas

Answer 12

Drop HbA1c by 15-20mmol.
Prevent microvascular complications (however not macrovascular)
More rapid effects than metformin

Question 13

Adverse effects of sulfonylureas

Answer 13

Weight gain
Hypoglycaemia risk (especially in elderly)

Question 14

Why might sulfonylureas fail to work in late stages of disease?

Answer 14

Sulfonylureas need functioning beta cells to work and in late stages of disease they may all be destroyed.

Question 15

Examples of TZD’s

Answer 15

Pioglitazone

Question 16

How do TZD’s work?

Answer 16

They work on nuclear receptors causing transcription of insulin sensitive genes.

Question 17

Positive effects of TZD’s

Answer 17

Increase fatty acid and triglyceride uptake (less likely to get DKA because less free fatty acids)
Increased sensitivity to insulin
Reduce hepatic glucose output
Prevent macrovascular complications (not microvascular)

Question 18

Adverse effects of TZD’s

Answer 18

Hypoglycaemia
Weight gain
Heart failure (due to them causing fluid retention because they promote Na+ reabsorption)

Question 19

When are TZD’s contraindicated?

Answer 19

In patients with osteoporosis or bone fractures

In patients with increased cardiovascular risk

Question 20

What are incretins?

Answer 20

GLP-1 or GIP drugs.

They stimulate hormones that increase the secretion of insulin from beta cells after meals.

Question 21

Positive effects of incretins

Answer 21

They reduce HbA1c
Weight loss
Increased insulin secretion
Decreased glucagon secretion
Slow gastric emptying

Question 22

Incretin analogues

Answer 22

Mimic the effects of incretins but are longer lasting.

They bind to GPCR GLP1 receptors that increase intracellular cAMP.

Question 23

Negative effects of GLP-1 drugs

Answer 23

Cause nausea

Have to be injected

Question 24

Example of a GLP1 drug?

Answer 24

Exenatide

Question 25

How do SGLT2 inhibitors work?

Answer 25

They inhibit the reabsorption of glucose in the proximal tubule of the kidney to deliberately cause glucosuria. They block S1 channels which is where 90% of the glucose is reabsorbed.

Question 26

Positive effects of SGLT2 inhibitors

Answer 26

Cause weight loss

Reduce CV risk

Question 27

Adverse effects of SGLT2 inhibitors

Answer 27

More likely to develop thrush and urine infections.

Question 28

Name some SGLT2 inhibitors

Answer 28

Dapagliflozin
Canagliflozin
Empagliflozin

Question 29

How do alpha glucosidase inhibitors work?

Answer 29

For dietary carbohydrate to be absorbed it needs to be in its monomer form. A brush border enzyme called alpha glucosidase does this. The drug works by delaying this enzyme therefore you don’t have the spike in blood glucose post prandially.

Question 30

Positive effects of alpha glucosidase inhibitors

Answer 30

No risk of hypoglycaemia.

Question 31

Adverse effects of alpha glucosidase inhibitors

Answer 31

GI upset- flatulence, abdominal pain, loose stools ect.

Question 32

Why would you maybe consider not using insulin therapy on obese patients?

Answer 32

For insulin therapy to work- you can’t have complete insulin resistance which tends to occur in people with obesity.