Type 1 Diabetes Flashcards
what are GAD antibodies characteristic of?
type 1 diabetes
rare presentation of T1DM?
headaches
muscle spasms
anxiety
how can T1DM be found incidentally?
GAD antibodies can appear on lumbar puncture
when in gestational diabetes diagnosed?
2nd or 3rd trimester of pregnancy
types of monogenic diabetes syndromes?
MODY
neonatal diabetes
type 1 vs type 2?
1 = absolute insulin deficiency 2 = relative insulin deficiency
what mediates type 1?
T cells
what other diseases is type 1 associated with?
other autoimmune diseases - thyroid, coeliac, addisons, pernicious anaemia, vitiligo
epidemiology of type 1?
genetic susceptibility
environmental trigger
prolonged prodrome (months to years)
80-90% loss of beta cell function before marked hyperglycaemia
what is LADA?
latent autoimmune diabetes of adulthood middle aged diagnosis so misdiagnosed as type 2 non-obese and slower onset HLA positive (GAD) low C peptide no family history mild IR 80% of those who are GAD positive are insulin dependant within 6 years
what is polyglandular endocrinopathy?
diseases associated with type 1
- ………
histology of type 1 and type 2 ?
type 1 = lymphocyte infiltration
type 2 = amyloid deposition
major islet antibodies?
IA-2 IA-2beta GAD Zn-T8 - all intracellular
how specific are islet autoantibodies?
present in 70-80% of new type 1 diagnoses
depends on age, gender, ethnicity and quality of assay
how can islet antibodies predict disease?
1 positive = 20-25% chance
2 present = 50-60% chance
3 present = 70% chance of developing T1DM within 5 years
most important autoantibody?
GAD
75-84%
………..
is there any genetic component to T1DM?
yes
increased risk if family member affected
genetic association with T1DM?
chromosome 6 HLA DR3, ………………
environmental effect on T1DM?
incidence higher in winter than summer
pathogenesis of T1DM?
beta cell mass decreases over time
immune dysregulation (event?) at early age decreases beta cell mass
environmental triggers and regulators and age cause mass to decrease further over time until diabetes presents when beta cells reach a certain low enough level
larger immune dysregulation event = earlier onset as beta cell mass has less to lose before reaching the point
main regulator of glucose homeostasis?
insulin and glucagon
interaction/balance of the two (especially in the liver) controls blood glucose levels
insulin functions?
increases glucose uptake (skeletal muscle)
decreases gluconeogenesis
decreases lipolysis (fat accumulation)
glucagon functions?
stimulates gluconeogenesis and lipolysis
features of insuin deficiency?
“accelerated starvation”
reduces glucose uptake in muscle so muscle wasting due to protein breakdown/catalysis
increases lipolysis so weight loss
counterregulatory effects of beta cell loss in T1DM?
alpha cells become less responsive
= alpha cell disregulation
how does T1DM present?
weight loss
fatigue
frequent urination (osmotic diuresis)
thirst
features of DKA?
vomiting abdominal pain altered consciousness acidotic breathing pH <7.3 dehydrated urine ketones +ve can lead to coma or death if untreated
which type is a family history more common in?
type 2
when does type 1 most commonly present?
pre school
peri-adolescence
small peak in 30s
60% <30 yrs
specific type 1 diagnosis?
history and presentation can be enough
autoantibodies more specific
how are insulin levels divided in normal people?
background insulin accounts for 50% - fairly constant level
meal time insulin accounts for 50% - varies with eating
problems with external insulin delivery?
given subcutaneously so need twice as much to get round circulation and into portal system where it would be produced normally
means everyone on insulin is hyperinsulinaemic
effects of high insulin as anabolic - hypertrophy, weight gain etc
what can day to day glucose variability in type 1 diabetics even when controlling condition with same insulin delivery every day?
failure to mix insulin adequately
accuracy of device
dynamics of delivery
leak from injection site
external factors - exercise, temperature
tissue - accidental injection into muscle, lipohypertrophy, blood supply
carbohydrate delivery - meal consituents, gsatroparesis
2 main types of insulin therapy?
meal time - lispro, aspart
long acting - glargine, detemir
function of insulin pump?
continuously regulates insulin by delivering specific insulin amounts?
best at maintaining basal levels
closed loop insulin?
sensor to sense glucose/insulin? levels and pump to deliver correct amount of insulin
what is DAFNE?
educational programme
dose adjusting for normal eating
risks of long term hyperglycaemia?
micro and macro vascular complications
- retinopathy
- nephropathy
- neuropathy
- MI/stroke
what is HbA1c?
glycated haemoglobin
glucose sticks to haemoglobin A1 so the more
how can glucose be monitored?
…
home blood glucose monitoring?
effective but not frequently used as inconvenient in daily life
need to measure pre and psost prandial
flash glucose monitoring?
abbot free style libre
can quickly measure glucose via device on arm at any time
smart insulin?
once a day self regulating insulin injection
causes glucose responsivity
not widely used?
