pathophysiology and treatment of T1DM Flashcards
what is the general phenotype of T1DM 8
lean
lose weight
symptomatic from the high glcuose
young
insulin deficient
what is the general phenotype of type 2 dm *
obese
insulin resistant
explain the ambiguity of the phenotypes *
older people (40) can present with insulin def - not have the penotype of type 1 - found to have ab to pancreas at late stage - were diagnosed with ‘latent aautoimmune diabetes in adults’ - now classify as t1dm
t2dm may present in childhood - increased prev of obesity
diabetic ketoacidosis can be seen in t2 - when they present, they’re insulin deficient because of irritation to panc - treat with insulin - then follow up with metformin to treat t2
genetic abnormlaity in B cells - monogenic dm presents as type 1 or 2 eg MODY and mitochondrial dm - strong FH at a young age
might be present following panc damage or other endocrine diseases eg pheaocytochroma or cusings, alcool damage panc = panc insufficiency
what is the prevalence of DM *
6-7% t2
in pop of lot of SA people - 10%
t1dm 0.25%
t2dm - majority of people with hyperglycaemia
describe the aetiology of t1dm *
environmental (incidence change through time of year - virus) and genetics (less than in t2)
these cause autoimmune destruction of the b cells - cause insuil deficiency
this causes yperglycaemia
describe the aetiology of t2 dm *
genetics and obesity
cause insulin resistance - at start a lot of insulin is produced then the b cells pack up
b cell failure
hyperglycaemia - need insulin in the end
describe the pathogenesis of t1dm *
may have period of high glucose but little bit of insulin still produced - then have severe insulin def happen very quickly - then have high glucose and low insulin (c-peptide measured - proetin that is bound to insulin)
b cell (immune) produce ab and ab attack the pancreas = b cell (panc) destruction = hyperglycaemia
suggestion that it is relapsing remitting - imbalance between effect t cells and those that control B cell proliferation - in lab big increase in b cells whic is what causses their destruction
wy is the immune basis of t1dm important
increased prev of other autoimmune conditions
risk of autoimmunity in relatives
if family as a lot of autoimmune conditions - individual is more at risk
more complete desctruction of b cells
auto-ab used clinically - measure ab - determine whether type 1 or type 2
immune modulation offers the potential of treatment - target the auto-ab - not happening now - b cells dont change therapy
how can you determine the genetic risk of t1dm *
look at the HLA markers - more done in research than practice
HLA-DR allelle on chromosome 6
DR3 and DR4 - significant risk of t1 dm
what can explain the seasonal prevalence in t1dm *
the env contribution to the aetiology - probably virus - incidence is higher in winter
what is suggested by the fact that there is different amounts of t1dm in differnet parts of the world *
there is environmental involvement
what are the places affected by t1dm *
sardinia in italy
what are the markers in t1dm *
islet cell ab (iCA) - group o human pancreas
isumin ab (IAA)
glutamic acid decarboxylase ab (gada) - widespread neurotransmitter
insulinoma-associated-2 autoab (IA-2A)- receptor like family
people with t1dm ave more of these ab than in normal pop or t2
symptoms of t1dm 8
polyuria
nocturia
polydipsia
blurring of vision
thrush
weight loss - make feeel ill
fatigue
what are the signs of t1dm *
dehydration
cachexia - if deficient for a while
hyperventialtion - kussmaul breathing - because of metabolic acidosis - try to blow off CO2
smell of ketones on breath
glucosuria
ketonuria
describe the effects of insulin def *
insulin reduces HGO - without iunsulin - glucose leaves liver
without glucose insulin acnt enter the muscle - so stays in the blood
insulin def also means aa are released from the muscle - enter the liver - turned into glucose = increased hgo
also TG broken down in adipose - insuin def mean glycerol and nefa leave adipose and enter liver
glycerol is converted to glucose = increase in HGO
without insulin fatty acids turned into ketone bodies (detect in circulation and urine) - enter muscle for energy - uptake not as good as glucose uptake
insulin inhibits all of these processes normally
what are the aims of treatment in t1dm *
reduce early mortalit
avoid acute metabolic decompensation
need exogenous insulin to live - maintain the metabolic imbalance
prevent long temr complications: retinopathy, nephropathym neuropathy, vascular disease (stroke/MI, peripheral arterial disease)
describe the recommended diet for t1dm *
reduce calories as fat
reduce calories as refined carb - otherwise glucose level is difficult to control
increase soluble fibre
balanced distribution of food over course of day with regular meals and snacks
where did we get insulin from before and where now
animals
humans
insulin anologues - now
what is the normal insulin profile *
have basal level of insulin and peak after meals (when glucose incraeses)
describe insulin treatment in t1dm *
try to mirror normal insulin profile
give long acting background insulin lasts for 18-24 hrs - bound to zinc or protamine - last longer - insulin analogue (glargine, determir, degludec)
give with meals - short acting, human insulin - more commonlu - insulin analogue (lispro, aspart, glulisine)
genetic engineering to alterr absorption, distribution, metabolism and excretion
give short acting with meal - flexibility - depend on the size of the meal and time of meal
can give 2 lots of long acting through day, or long acting at night, or very long acting for 24 hrs
what does an insulin pump do *
gives continuous insulin delivery
has programmed basal rates
pt gives bolus when have meals
doesnt measure glucose level - so not a feedback loop
what are the conditions for an insulin pump
funding difficult
have to ave poorly controlled insulin or severe hypoglycaemic episodes
describe the principle of islet transplants *
rare
iselt cells inserted through the portal vein into liver and redistributed through body
wy are iselt cells rare *
have to be on immunosuppressants for all life
have to be v severe
waiting list long
describe the 2 methods of capillary monitoring *
CGM - continuous glucose monitoring - give real time reading - not ass accurate as venous reading
prick fingers - measure in blood - not as accurate as venous
give an idea of trend
when do you have to check glucose *
before injecting insulin
what ddo you do with the info from CGM *
see when hypos and hypers occured and try to decide why eg didnt inject enough insulin or forgot to eat etc
how can we tell CGM is a good tool
HBA1c has reduced in people using it
describe HBA1c readings for glucose *
red cell reacxt with glucose - irrreversible, non covalent bond
depend on red cell life span- rate of glycation faster in some individuals - if have sickle cell/renal disease - hba1c not reflective
gives an idea of glucose control for 3months - 120 days is normal lifespan of red cells
show you the level of glucose
forms an ideal measure of long term control and is related to risk of complications
lowering hba1c associated with lower risk of micro and macrovascular complications
what are the acute complications of t1dm *
come to hospital v sick
hyperglycaemia - reduced tissue glucose utilisation and increased go
severe met acidosis low ph, bicarb and co2- have circulating acetoacetate and hydroxybutyrate = osmotic deydration and poor tissue perfusion
what is t1dm *
absolute insulin deficiency
ketone prone dm
classified by aetiology and phenotype
define hypoglycaemia *
plasma glucose <3.6mmol/l
define severe hypoglycaemia *
any hypo requiring help of another person to treat - paramedic
what is the problem with people fearing hypos *
prefer to be hyper - has complications too
why are hypos importantb
most mental processes impaired <3mmol/l
consciousness impaired <2mmol/l
severe may cause arrhythmia and death
long term effects on brain
recurrent hypos = loss of warnings - dont get symptoms so suddenly become unconscious - ‘hypoglycaemia unawareness’ - autonomic change means not aware
who is at risk of a ypoglycaemia *
main risk factor is quality of glycaemic control - people who aim for really tight control over do it
more freq in pts with low hba1c
when are hypoglycaemias more likely to occur *
anytime but often clear pattern
pre lunch/dinner
nocturnal hypos common - not always recognised - body make catecolamines when have hypo = high glucose in morning - need cgm to see if had hypo
why do hypos occur *
unaccoustemed exercise - and dont eat more or change insulin
miss meals in attempt to lose weight
inadequate snacks
alcohol - have too much and dont give insulin
inappropriate insulin regieme - miscalculate how much to give
what are the signs and symptoms of hypoglycaemia due to increased autonomic activation *
palpitations - tachycardia
tremor
sweating
pallor/cold extremities
anxiety
what are the signs and symptoms of hypoglycaemia due to impaired CNS function *
drowsiness
confusion
altered behhaviour
focal neurology
coma
how do you treat hypoglycaemia *
feed pt - glucose gel or tablet - then complex carb so have glucose when simple glucose has been used
if unconcious - give paranatal - IV destrose eg 10% glucose infusion, 1mg IM glucagon - cause glucose to be released out of liver - put if fasting glucose reserves will have been used so this wont work,. avoid concentrated solutions in possible eg 50% glucose
vcan be trained to use glucagon themselved then treat with iv glucose when come into hospital
how do you prevent hypos *
regualrly measure blood sugar
dont miss meals
always carry sugary snack
carry glucoiagon injection kit
dont drink too much alcohol in shrot space of time or on empty stomach
eat carby snack before exercise
eat carby snack before sleep
what is the scheme for t1dm diet management
DAFNE
dose adjustment for normal eating
provide you wit skills to estimate te right level of carbohydrate in each meal
