Glycaemic control in long-established diabetes Flashcards
What are the major modifiable risk factors for macrovascular disease?
Diabetes Hypertension Smoking Dyslipidaemia Lack of exercise
What is the mechanism of action of the Sulfonylureas?
Increase pancreatic insulin secretion.
In which patients would the Sulfonylureas be used as a first-line treatment?
Patients with type 2 diabetes in whom hypoinsulinaemia (rather than insulin resistance) is the predominant cause of hyperglycaemia
What are four examples of sulfonylureas?
Glibenclamide
Gliclazide
Glipizide
Glimepiride
How are sulfonylureas used in most T2DM patients?
as second-line treatment, after metformin
What is the mechanism of action of Thiazolidinediones?
Increase peripheral insulin sensitivity.
Decreases hepatic glucose output.
( Agonist of peroxisome proliferator-activated receptor gamma, which regulates genes involved in lipid and glucose metabolism)
How are Thiazolidinediones used in glycaemic control?
Reserve for patients unable to take other antidiabetics
Name 2 Thiazolidinediones
Rosiglitazone
Pioglitazone
What is the mechanism of action of acarbose?
Reduces carbohydrate absorption in gut. Prevents the breakdown of polysaccharides to monosaccharides. (e.g. sucrose to glucose)
To which group of drugs does metformin belong?
Biguanides
What is the mechanism of action of metformin?
The glucose-lowering, insulin-sensitizing agent metformin works mainly by reducing gluconeogenesis and opposing glucagon-mediated signalling in the liver and, to a lesser extent, by increasing glucose uptake in skeletal muscle
The primary site of metformin action is the mitochondrion
The antihyperglycaemic effect of metformin is probably owing to defective protein kinase A signalling
Metformin affects lipid metabolism primarily via 5′-AMP-activated protein kinase (AMPK) activation
What tests are performed to monitor the microvascular complications of diabetes?
neuropathy: clinical examination
nephropathy: urine albumin creatinine ratio
retinopathy: ophthalmological retinal screening
What are the microvascular complications of diabetes?
Neuropathy
Nephropathy
Retinopathy
What is a possible complication of using sulfonylureas?
Hypoglycaemia
What is the first line treatment for T2DM?
Metformin
What is the major side effect of Metformin?
Gastrointestinal upset (1/3 of patients)
What is the daily dose of Metformin?
250-1000mg daily
How is metformin cleared from the body?
Renally (100%)
What is the mechanism of action of GLP-1 Analogues?
Analogues of glucagon-like peptide‑1 (an incretin);
- increase glucose-dependent insulin secretion
- suppress inappropriate glucagon secretion.
- delay gastric emptying, which slows glucose absorption,
- decrease appetite.
What is an example of a GLP-1 Analogue?
Semaglutide
Exenatide
Dulaglutide
Liraglutide
What is the mode of administration of exenatide?
Subcutaneous
What is the dosing regimen for exenatide?
Initially 5mg SC BD
If tolerated, 10mg SC BD
What is the mechanism of action of DPP-IV inhibitors?
Stimulate insulin secretion and suppress glucagon release by increasing concentrations of GLP-I and related peptides by blocking their metabolism.
How are DPP-IV inhibitors used to treat T2DM?
In combination with metformin or a sulfonylurea
What is the name of a DPP-IV inhibitor?
Sitagliptin Linagliptin Saxagliptin Alogliptin Vildagliptin
How is sitagliptin cleared from the body?
Renally (100%)
In which patients are Thiazolidinediones contraindicated?
In patients with heart failure.
How often should one monitor HBA1c levels?
HbA1c most accurately reflects the patient’s glycaemic control for the previous eight to 12 weeks. Testing every 3 months is sufficient.
How can patients mitigate the gastrointestinal side-effects of metformin?
Taking with meals, gradual dose titration or using the extended release preparation.
What is one rare but significant risk of metformin usage? And what feature of a patient would make this outcome more likely?
Lactic acidosis. Renal impairment.
What proportion of patients will not respond to thiazolidinediones?
up to 1/3
What are the common adverse effects of sulfonylureas?
Weight gain and hypoglycaemia
What are the benefits of initiating insulin therapy early?
Potentially improves or preserves beta-cell function
Prevents loss of glycaemic control
Reduces the risk of microvascular complications.
