diabetes & insulin Flashcards
does insulin resistance cause increased risk of alzheimer’s?
yes
what causes insulin production to fall as insulin resistance increases in type 2 diabetes?
B- cell dysfunction
what factors in type 2 diabetes cause heart failure?
hyperlipidemia and hyperglycaemia
does insulin resistance have symptoms?
no
what are the 3 mechanisms of insulin resistance?
impairment of insulin signalling (e.g. skeletal muscle insulin resistance)
inflammation (e.g. adipose tissue insulin resistance)
pathways selective hepatic insulin resistance
what is the gold standard for measurement of insulin sensitivity?
hyperinsulinemic-euglycemic clamp
how is insulin resistance reversed?
eating less, exercise, medication
what is the definition of diabetes?
loss of glucose homeostasis leading to hyperglycaemia
what fasting blood glucose level is classed as hyperglycaemia?
> 7mM
what fasting blood glucose level indicates pre-diabetes?
6-7mM (4-6 would be normal, and <4 is hypoglycaemia)
what do the different cells of pancreatic islets secrete?
alpha cells - secrete glucagon
beta cells - secrete insulin
delta cells - secrete somatostatin
PP cells - secrete pancreatic polypeptide
where is insulin synthesised?
rough endoplasmic reticulum of pancreatic beta cells as preproinsulin
it is then cleaved to form insulin
what is the structure of insulin?
2 polypeptide chains linked by disulfide bonds and a connecting peptide
what is the shortest acting insulin?
insulin lispro
what is the longest acting insulin?
insulin glargine- can be administered as a single bedtime dose
what are the 2 phases of insulin release?
5 % of insulin granules are immediately available for release – RRP – readily releasable pool
Reserve pool must undergo preparatory reactions to become mobilised and available for release
what happens to insulin release in T2DM?
In poorly controlled T2DM insulin secretion weakens and flattens.
This is likely due to downregulation of the sensing process (e.g. limited glucokinase activity flux, mitochondrial exhaustion –> reduced ATP production, or run down of insulin stores).
how do sulphonylureas work?
they mimic the action of ATP to depolarise beta cells
what is type 1 diabetes?
autoimmune destruction of pancreatic beta cells
what do you need to diagnose type 1 diabetes?
presence of specific antibodies and declining C-peptide production.
how do you diagnose gestational diabetes?
FBG > 5.5
declining beta cell function
diagnosed in the second or third trimester
how do you treat gestational diabetes and what are the risks?
metformin and lifestyle advice
big risk factor for developing T2DM in future (12x increased risk)
what is MODY?
maturity onset diabetes of the young
has common features of types 1 & 2
monogenic diabetes with beta cell dysfunction but no autoimmune destruction
can be misdiagnosed as type 1
what is donohue syndrome (leprechaunism)?
- Rare autosomal recessive mutation in the insulin receptor gene
- Severe insulin resistance
- Developmental abnormalities
– elfin facial appearance
– growth retardation
– absence of subcutaneous fat, decreased muscle mass - Caused by defects in insulin binding or insulin receptor signalling
what is rabson mendenhall syndrome?
- Rare autosomal recessive genetic trait
- Severe insulin resistance, hyperglycemia and
compensatory hyperinsulinemia - Developmental abnormalities
- Acanthosis nigricans (hyperpigmentation)
- Fasting hypoglycaemia (due to hyperinsulinemia)
- Diabetic ketoacidosis
- Severe cases linked to mutations in the insulin receptor that reduce sensitivity
what are the symptoms of diabetic ketoacidosis?
Vomiting
Dehydration
Increased heart rate
Distinctive acetone smell on breath
what is the most common cause of diabetic ketoacidosis?
type 1- not taking insulin properly e.g. missing a dose
what are the diagnostic thresholds of blood glucose?
random or 2 hr glucose >=11.1mmol/L
or
fasting glucose >=7mmol/L
or
HbA1c >= 48mmol/L
if asymptomatic, repeat confirmatory test must also be done
threshold is set on relation to the risk of diabetic retinopathy
what are the threshold levels for gestational diabetes set by?
risk to foetus (not retinopathy)
what is a marker of endogenous insulin secretion?
C-peptide - can show how well the pancreas is working
what are the symptoms of high blood glucose?
Polyuria
Thirst and polydipsia
Blurred vision
Genital Thrush
Fatigue
Weight loss
can rarely also have loss of vision or retinal changes
what is the HbA1c?
measure of the amount of glycated haemoglobin (glucose attached to haemoglobin) over 90 days
what is Hb1Ac measured in?
mmol/mol (used to be %)
what is the target HbA1c in patients with type 2 diabetes on treatment?
53mmol/mol (7%)
a target of 48mmol/mol (6.5%) can be used at diagnosis.
targets can be individualised to patients.
what is the glycaemic index (GI)?
rank of rate at which food makes blood glucose rise
what type of exercise causes hyperglycaemia?
Anaerobic activity, competition or insufficient insulin
Avoid exercise if BG >14 mmol/L or ketones present (additional fast acting insulin may be required)
what are the 2 types of prandial insulins and what is the difference between them?
insulin analogues-
onset 10-15 mins
peak action 60-90 mins
duration 4-5 hours
soluble insulin-
onset 30-60 mins
peak 2-4 hours
lasts 5-8 hours
what are the 2 types of basal insulins and what are the differences?
isophane ‘basal’ insulins-
intermediate/long acting
peak after 4-6 hours
analogue basal insulin-
long duration of action
less peak activity (flatter profile)
can be given once or twice a day
what type of insulin should most T1DM patients be on?
analogue basal insulin (e.g. glargine)
when is diabetes found in cystic fibrosis?
CTRDM is found in >25% at 20 years
usually found in severe mutations
prone to complications
preferrebly insulin treated
what types of pancreas transplantation are there?
kidney-pancreas transplant- end stage renal failure, severe hypo or metabolic complication, incapacitating clinical/ emotional problems, high chance of rejection
islet autotransplantation- same indications to receive
when would you consider weight reduction surgery in diabetes?
BMI over 40, or BMI over 35 with obesity related co-morbidity e.g. T2DM
what is the risk of a child getting T1DM if both parents have it?
30%
what is the risk of a child getting T2DM if both parents have it?
around 70% (40% if only 1 parent has it)
