revison Flashcards
What is diabetes mellitus
symptoms of type 1 and type 2
diagnosis
causes of type 1 diabetes
treatment of type 1
side effects
A common group of metabolic disorders that are characterised by chronic hyperglycaemia.
symptoms;
Symptoms of Type I diabetes are often acute:
2-4 week history of thirst, polyuria, weight-loss, lethargy.
Symptoms of Type II diabetes are often sub-acute and less marked:
History of thirst, polyuria, lethargy, visual disturbances, infections, which occur over several months.
diagnosis
Detection of glucose in urine (not definitive).
Random venous plasma glucose test (≥11.1mmol/L is suggestive of diabetes).
Fasting venous plasma glucose test (≥7.0mmol/L is suggestive of diabetes).
Oral glucose tolerance test (is used if borderline diagnosis, or in gestational diabetes screening).
Glycated haemoglobulin (HbA1c) levels of ≥6.5% (48mmol/mol) in some people with diabetes (WHO, 2011).
causes
Type I diabetes is characterised by complete insulin deficiency.
Complete insulin deficiency normally results from autoimmune destruction of insulin-secreting pancreatic beta-cells.
treatment
Treatment aims to provide insulin replacement in a way that mimics the insulin secretion pattern observed in individuals without diabetes.
side effects:
redness, swelling, and itching at the injection site.
changes in the feel of your skin, skin thickening (fat build-up), or a little depression in the skin (fat breakdown)
weight gain.
constipation.
what is the treatment of type 2 diabetes
Lifestyle interventions (first line)
Diet and weight loss
Exercise,
Education
Then add drug treatments:
Oral hypoglycaemic agents
Insulins
what is the mechanism of action of blood glucose lowering medicines?
- drug classes and location
LIVER - biguanides and thiazolidineodiones reduces glucose production
-SMALL intestine - alpha- glucosidase inhibitors slow down absorption of sucrose and starch
-PANCREAS - GLP-1 (incretins) improve response to glucose levels
insulin secretogogues: sulphonylureas and megiltitnides increase insulin production
-SKELETAL MUSCLE and ADIPOSE TISSUE - thiazolidinediones and biguanides reduce insulin resistance
what is insulin sensitisers and examples?
Enhance the effect of endogenous circulating insulin, increasing the sensitivity of peripheral tissues to insulin and decreasing glucose production in liver
Biguanide, metformin, and thiazolidinediones (“glitazones”) are insulin sensitisers
what is the drug class of metformin, aims, common side effects and cautions.
moa
Metformin is the only biguanide currently available and is the “first line” treatment for type II diabetes
moa : It activates energy sensor AMP kinase which promotes cellular energy uptake
Suppresses appetite, helps achieve weight loss and has a cardio-protective effect (reduced mortality and morbidity)
Common side effects (e.g. abdominal pain, nausea, diarrhoea) minimised by gradual increases to reach therapeutic dose or by modified release formulations
Metformin cannot be used in patients with renal impairment, cardiac failure or liver failure as it is associated with lactic acidosis (potentially fatal)
what is the mode of action of thiazoldinediones?
Bind to peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and, through regulation of gene transcription, enhance glucose and fatty acid uptake and utilisation in adipocytes, reduce secretion of cytokines that inhibit insulin action
Reduced availability of fatty acids in muscle improves insulin sensitivity
Reduce hepatic glucose output
Can take up to 3 months to see maximal effect as have indirect effect on blood glucose but, once achieved, effect is comparable to metformin and sulphonylureas
what can glitazones increase the risk of? - pioglitazone
cardiovasular
what is insulin secretagogues
Stimulate insulin release from the pancreas
Aim to restore early phase insulin release and return plasma insulin levels to pre-prandial levels rapidly to avoid post-meal hypoglycaemia
Sulphonylureas and meglitinides are insulin secretogogues
what is the moa of Both sulphonylureas and meglitinides
close K+ ATP channel but do so by binding to different (but related receptors)
name a short acting Sulphonylureas
gliclazide or tolbutamide
what is long acting sulphonyureas
glibenclamide
what is the moa of sulphonylurea
common side effects
Increase insulin release from the pancreas by binding to sulphonylurea receptor, closing the K+ ATP channel, which causes a rise in intracellular calcium and insulin release
Typically will reduce HbA1c by 1.5-2%.
Common side effects include weight gain (not first choice for overweight patients).
Can cause sustained hypoglycaemia (worse in elderly or with hepatic impairment; often requiring hospital treatment)
Can be used in combination with insulin sensitisers
