Insulin and Hypoglycaemics Flashcards
What is glucosuria
elevated glucose levels saturate the glucose re-uptake mechanisms in the kidneys
diagnostic of underlying pathology = diabetes mellitus
leads to osmotic diuresis = thirst, dehydration, increased urine output, unconsciousness, death!
Homeostasis of hypergylcaemia
food intake/endogenous glucose production =
increase in plasma glucose =
insulin release from pancreatic B cells =
insulin action in liver, muscles, CNS =
decrease plasma glucose
Homeostasis of hypoglycaemia
fasting =
decrease in plasma glucose =
glucagon release by pancreatic A cells =
endogenous glucose production, action on liver, muscles, CNS =
increase in plasma glucose
Pancreatic Islets of Langerhans
approx. 1.5 mil per pancreas contain different cell types: - B cells that release insulin - A cells that release glucagon PP cells that release pancreatic polypeptide E cells that release ghrelin
How does glucose stimulate insulin release?
food intake = digestion = glucose uptake by B cells = inhibition of Katp channels (molecules which close K-channels mimic actions of glucose, used to treat hyperglycaemia - insulin secretagogues - . molecules which open K-channels inhibit the actions of glucose, used to treat hypoglycaemia - hypeglycaemia-inducing drugs) = depolarization of the cell = calcium influx = insulin release.
Glucose homeostasis; integration with digestion
food intake =
digestion =
release of gut hormones =
rise in serum GLP-1 =
activation on the GLP-1 receptor (incretin effect)=
cell signalling =
insulin release.
oral glucose faster insulin response compared to i.v
- glucagon-like peptide 1 and gastric inhibitory peptide are incretin hormones
Functional effects of insulin
increases glucose - glycogen (stored in skeletal muscle, liver)
increases glucose - fat (stored as adipose tissue)
increases amino acids - proteins (muscle)
increases glucose and amino acid transport to cells
decreases glycogen breakdown
decreases glucose formation (gluceoneogenesis)
Insulin therapy
treatment for people with type 1 diabetes mellitus
3 preparations:
- short duration; rapid onset (30-60 mins)
soluble insulin and rapid onset insulin analogues: eg. insulin aspart, insulin glulisine, insulin lispro (s.c, i.v)
- intermediate action
eg. isophane insulin; can be porcine, human or bovine (s.c)
- longer lasting; slow onset and lasts for longer
eg. protamine zinc suspension - porcine, human or bovine (s.c)
insulin detemir, insulin glargine - recombinat human (s.c)
What are the 3 preparations in insulin therapy made up of?
short duration - insulin aspart, insulin glulisine, insulin lispro (s.c, i.v)
intermediate action - isophane insulin; can be porcine, human or bovine (s.c)
longer lasting - protamine zinc insulin, insulin zinc suspension - porcine, human or bovine (s.c)
insulin detemir, insulin glargine - recombinant human (s.c)
Short action insulin
peal action 2-4 hours
duration of 8 hours
injected just before or just after food, only lasts long enough for meal at which it was taken
Intermediate/longer acting insulin
onset 1-2 hours
peak action 4-12 hours
duration is 16-35 hours
Biphasic insulin preperations
mixture of intermediate and fast acting
rapid onset
longer-lasting actions
Eg. biphasic insulin aspart and lispro, biphasic isophane insulin
Other treatments for type 1 diabetes mellitus
islet/pancreas transplantation
prevention: immune-mediated destruction of B-cells
Insulin administration
subcut injection 3-4 times daily
- used needle/syringe pens
- portable infusion pump of continuous short acting insulin infusion
Glucagon therapy
for hyperglycaemia-inducing: first treatment for severe hypoglycaemia when oral glucose is not possible - given m=by i.m, i.v, s.c to increase plasma glucose levels - SE = nausea, headaches - glucagon promotes > glycogenolysis > gluconeogenesis > lipolysis
Sulphonylureas
Secretagogues I
oral treatment for hypoglycaemia in type 2 diabetes mellitus
boosts insulin release
small molecule antagonist of the Katp channel receptor
oral agents: 1/2 doses daily before or with a meal
- short acting:
eg. Tolbutamide (Sulphonylureas)
longer lasting:
eg. Chlorpropamide, Glibenclamide (Sulphonylureas)
risk of hypoglycaemia with both
Prandial glucose regulators/ Meglitinides
Secretagogues I oral treatment for hypoglycaemia in type 2 diabetes mellitus boosts insulin release eg. Nateglinide decreased risk of hypoglycaemia
Diazoside
used to treat congenital hyperinsulism in infancy
small molecule antagonist of the Katp channel
SE = anorexia, nausea and vomiting, hypotension, tachycardia, arrhythmias
Exenatide/ Liraglutide
secretagogues II - incretin mimetic injectable agent, s.c combined with other therapies reduced risk of hypoglycaemia eg. Byetta SE = GI disturbances, dizziness, headaches
DPP-4 inhibitors/ Gliptins
secretagogues III incretin mimetic inhibitors of DPP-4 oral tablet eg. Sitagliptin, Vildagliptin can be combined with other medications SE = GI disturbances, peripheral oedema, headache, upper respiratory infections
Biguanides
insulin sensitiser - improves sensitivity of target organs to insulin
2 modes of action:
- prevents hepatic production of glucose
- improves insulin sensitivity
eg. Metformin
- taken up to 3 times a day, immediately after a meal
- doesn’t cause weight gain, best choice for patients who have heart failure
available in combination
Thiazolidinediones/ Glitazones
insulin sensitiser - improves sensitivity of target organs to insulin
oral; one/two times daily
activates a regulatory protein involved in transcription of insulin-sensitive genes which regulate glucose and fat metabolism
principle target = adipocytes
eg. Pioglitazone
history of concerns in aptients wth diabetes and ischaemic heart disease
Alpha glucosidase inhibitor
delay glucose absorption
eg. Acarbose
- a-glucosidase converts oligosaccharides to glucose
- acarbose inhibits this enzyme
absorption of starchy foods in slowed = slowing-down rises n plasma glucose following a meal
SE = flatulence, diarrhoea, nausea, indigestion, intestinal problems
SGLT2 inhibitors (flozins)
Sodium-coupled glucose transporter
promote glucose loss in the urine to reduce hyperglycaemia
potential advantages: weigh loss, insulin independent,
eg. Dapagliflozin, Canagliflozin
