Poster 2- treatment of diabetes Flashcards
Generalised treatment of type 1 diabetes
Insulin therapy to get glycemic control. Done using a basal bolus regimen
Generalised treatment of type 2 diabetes
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.
Treatment ladder for type 2 diabetes
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.
Metformin is a….. drug
Biguanide
Metformin does…. to the body
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
Dosage of metformin
Max- 3g daily
Usually start on 500g OD or BD
Positive outcomes for patients on metformin
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
Which drugs can metformin be used alongside
Sulphonylureas, glitazones and insulin
Examples of sulfonylureas and their doses
Glicazide (40mg OD to 160mg BD)
Glipizide (2.5mg to 15mg)
Glibenclamide
How do sulfonylureas work?
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.
Describe the Katp channel
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.
Positive effects of sulfonylureas
Drop HbA1c by 15-20mmol.
Prevent microvascular complications (however not macrovascular)
More rapid effects than metformin
Adverse effects of sulfonylureas
Weight gain Hypoglycaemia risk (especially in elderly)
Why might sulfonylureas fail to work in late stages of disease?
Sulfonylureas need functioning beta cells to work and in late stages of disease they may all be destroyed.
Examples of TZD’s
Pioglitazone
How do TZD’s work?
They work on nuclear receptors causing transcription of insulin sensitive genes.
Positive effects of TZD’s
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)
Adverse effects of TZD’s
Hypoglycaemia
Weight gain
Heart failure (due to them causing fluid retention because they promote Na+ reabsorption)
When are TZD’s contraindicated?
In patients with osteoporosis or bone fractures
In patients with increased cardiovascular risk
What are incretins?
GLP-1 or GIP drugs.
They stimulate hormones that increase the secretion of insulin from beta cells after meals.
Positive effects of incretins
They reduce HbA1c Weight loss Increased insulin secretion Decreased glucagon secretion Slow gastric emptying
Incretin analogues
Mimic the effects of incretins but are longer lasting.
They bind to GPCR GLP1 receptors that increase intracellular cAMP.
Negative effects of GLP-1 drugs
Cause nausea
Have to be injected
Example of a GLP1 drug?
Exenatide
How do SGLT2 inhibitors work?
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.
Positive effects of SGLT2 inhibitors
Cause weight loss
Reduce CV risk
Adverse effects of SGLT2 inhibitors
More likely to develop thrush and urine infections.
Name some SGLT2 inhibitors
Dapagliflozin
Canagliflozin
Empagliflozin
How do alpha glucosidase inhibitors work?
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.
Positive effects of alpha glucosidase inhibitors
No risk of hypoglycaemia.
Adverse effects of alpha glucosidase inhibitors
GI upset- flatulence, abdominal pain, loose stools ect.
Why would you maybe consider not using insulin therapy on obese patients?
For insulin therapy to work- you can’t have complete insulin resistance which tends to occur in people with obesity.
