Type 2 Diabetes Flashcards
What is Type 2 diabetes characterised as?
Tissue insensitivity to insulin action (insulin resistance) and inability of pancreas to adapt so overproduction of glucose
What are the core 2 physiological changes in type 2 diabetes?
Insulin resistance and B-cell dysfunction (genetic)
What actually is insulin resistance?
Down stream pathway – the receptor is not as responsive to the insulin molecule and therefore less glucose enters the cell. This results in a build up of glucose in the blood
What causes insulin resistance?
- Ectopic Fat Accumulation and increase FFA circulation
- Increase Inflammatory mediators (CRP)
What is the classic clinical presentation for T2DM?
- Middle-aged/eldery
- obese
- often CVD/pre-diabetic symptoms beforehand
What signs may there be on examination of T2DM?
Acanthosis Nigrocans (hyper pigmentation of the skin) Signs of other endocrine diseases eg. Cushings
What is the timeline of T2DM?
- Insulin resistance occurs and initially the beta -cells compensate by producing more insulin
- However eventually the resistance overcomes the production and hyperglycaemia and elevated FFAs causes beta-cell function declines, due to the glucotoxicity and lipotoxicity
- Then blood glucose levels increase
True/False: Diabetes can be reversed by diet change
True, by reducing fat levels in the pancreas
What conditions are associated with T2DM in terms of PMH?
- Gestational diabetes
- Polycystic Ovarian Syndrome
- Pancreatitis
- Cystic fibrosis/Myotonic dystrophy
What is the general action of Biguanides, and which is the main example?
Insulin sensitisers and also reduces hepatic gluoconeogenesis - Metformin
True or False: Biguanides should not be given at a larger dose than 1g
True, there is little evidence of benefit
Which T2DM medications are at risk of causing hypos?
Sulphonylureas
Which T2DM medications are weight neutral?
Metformin (Biguanides), DPP-IV inhibitors
What are the main side effects of metformin (Biguanides)?
Lactic acidosis, GI effects (nausea, DandV), liver failure and rash
What is the first line treatment for T2DM?
Metformin
What is the general action and example of Sulphonylureas (SU)?
Insulin secretagogues - Glibencalmide, Gliceride, glipizide and glimepiride
What is the mechanism of action of sulphonylureas?
SU bind to the sulphonylurea receptor subunits of KATP channels in the pancreatic β-cells, causing them to open independent of plasma glucose concentration to promote insulin secretion
Which T2DM medications can cause weight gain?
Sulphonylureas and Thiazolidinediones
Which T2DM medications shouldn’t be used in patients with renal or hepatic failure?
Sulphonylureas but also Metformin (biguanides)
What is the general action and example of Thiazolidinediones (TZDs)/glitazones?
PPARγ agonists decreasing insulin resistance at target tissues - Pioglitazone
In what age group are Thiazolidinediones (glitazones) not recommended?
>65y, due to the risk of hip fracture and heart failure
What are the main side effects of Thiazolidinediones (glitazones?
Heart failure (due to fluid retention)
What is the incretin effect?
Glucose which enters the body orally and is digested will produce a higher insulin response (more insulin) than if it was given IV. This is because when the oral glucose reaches the stomach and duodenum, it stimulates the release of digestive hormones (gastrin, GIP, CCK, Secretin) which can further enhance insulin secretion.
What are examples of incretins?
GIP from K cells and GLP-1 from L cells (Hormones from intestines which stimulate insulin secretion in response to glucose)
What is the general action and example of GLP-1 Receptor Agonists/Incretin analogues?
Promote insulin secretion by simulating incretins (but are longer lasting) - Liraglutide, Exanatide and Lixisenatide
What is the general action and example of DPP-IV Inhibitors?
Inhibit the enzyme which breaks down incretins (DPP-4) - Vildagliptin, Sitagliptin, Saxagliptin, Linagliptin
What is the general action and example of SGLT2 Inhibitors?
Block glucose reabsorption and promote excretion - Dapagliflozin, Canagliflozin and Empagliflozin
Which T2DM medications can cause weight loss?
GLP-1 Receptor Agonists and sometimes Biguanides (Metformin)
What are the main side effects of SGLT2 inhibitors?
Increase in thrush and UTIs
Which form of insulin regime is mostly used in T2DM?
Basal insulin (less use of basal-bolus)
What T2DM medications are insulin dependent?
- Those increasing secretion of insulin: (e.g. sulfonylureas, incretin mimetics, glinides, DPP-4 inhibitors (gliptins)
- Those decreasing insulin resistance e.g. biguanides, thiazolidinediones (glitazones)]
Which T2DM medications are insulin independent?
- α-glucosidase inhibitors
- Sodium glucose type-2 (SGLT2) inhibitors]
What is the general action and example of Glinides (Meglitinides)?
Insulin secretagogues - repaglinide and nateglinide
What is the mechanism of action for Glinides (Meglitinides)/
Act similarly to the sulfonylureas – bind to SUR1 (at a distinct benzamido site) to close the KATP channel and trigger insulin release
What is the general action and example of a-Glucosidase Inhibitors?
Inhibitors of a-glucosidase (duh) which normally breaks down starch and disaccharides to absorbable glucose - Acarbose
What is the mechanism of action of Thiazolidinediones (TZDs, Glitazones)?
- Act as exogenous agonists of the nuclear receptor PPARg) which associates with retinoid receptor X (RXR) - PPARg is largely confined to adipocytes.
- Activated PPARg-RXR complex acts as a transcription factor that binds to DNA to promote the expression of genes encoding several proteins involved in insulin signalling, among other - Promote fatty acid uptake and storage in adipocytes, rather than skeletal muscle and liver
