pathophysiology and treatment of T1DM

Question 1

what is the general phenotype of T1DM 8

Answer 1

lean

lose weight

symptomatic from the high glcuose

young

insulin deficient

Question 2

what is the general phenotype of type 2 dm *

Answer 2

obese

insulin resistant

Question 3

explain the ambiguity of the phenotypes *

Answer 3

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

Question 4

what is the prevalence of DM *

Answer 4

6-7% t2

in pop of lot of SA people - 10%

t1dm 0.25%

t2dm - majority of people with hyperglycaemia

Question 5

describe the aetiology of t1dm *

Answer 5

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

Question 6

describe the aetiology of t2 dm *

Answer 6

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

Question 7

describe the pathogenesis of t1dm *

Answer 7

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

Question 8

wy is the immune basis of t1dm important

Answer 8

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

Question 9

how can you determine the genetic risk of t1dm *

Answer 9

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

Question 10

what can explain the seasonal prevalence in t1dm *

Answer 10

the env contribution to the aetiology - probably virus - incidence is higher in winter

Question 11

what is suggested by the fact that there is different amounts of t1dm in differnet parts of the world *

Answer 11

there is environmental involvement

Question 12

what are the places affected by t1dm *

Answer 12

sardinia in italy

Question 13

what are the markers in t1dm *

Answer 13

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

Question 14

symptoms of t1dm 8

Answer 14

polyuria

nocturia

polydipsia

blurring of vision

thrush

weight loss - make feeel ill

fatigue

Question 15

what are the signs of t1dm *

Answer 15

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

Question 16

describe the effects of insulin def *

Answer 16

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

Question 17

what are the aims of treatment in t1dm *

Answer 17

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)

Question 18

describe the recommended diet for t1dm *

Answer 18

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

Question 19

where did we get insulin from before and where now

Answer 19

animals

humans

insulin anologues - now

Question 20

what is the normal insulin profile *

Answer 20

have basal level of insulin and peak after meals (when glucose incraeses)

Question 21

describe insulin treatment in t1dm *

Answer 21

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

Question 22

what does an insulin pump do *

Answer 22

gives continuous insulin delivery

has programmed basal rates

pt gives bolus when have meals

doesnt measure glucose level - so not a feedback loop

Question 23

what are the conditions for an insulin pump

Answer 23

funding difficult

have to ave poorly controlled insulin or severe hypoglycaemic episodes

Question 24

describe the principle of islet transplants *

Answer 24

rare

iselt cells inserted through the portal vein into liver and redistributed through body

Question 25

wy are iselt cells rare \*

Answer 25

have to be on immunosuppressants for all life have to be v severe waiting list long

Question 26

describe the 2 methods of capillary monitoring \*

Answer 26

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

Question 27

when do you have to check glucose \*

Answer 27

before injecting insulin

Question 28

what ddo you do with the info from CGM \*

Answer 28

see when hypos and hypers occured and try to decide why eg didnt inject enough insulin or forgot to eat etc

Question 29

how can we tell CGM is a good tool

Answer 29

HBA1c has reduced in people using it

Question 30

describe HBA1c readings for glucose \*

Answer 30

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

Question 31

what are the acute complications of t1dm \*

Answer 31

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

Question 32

what is t1dm \*

Answer 32

absolute insulin deficiency ketone prone dm classified by aetiology and phenotype

Question 33

define hypoglycaemia \*

Answer 33

plasma glucose \<3.6mmol/l

Question 34

define severe hypoglycaemia \*

Answer 34

any hypo requiring help of another person to treat - paramedic

Question 35

what is the problem with people fearing hypos \*

Answer 35

prefer to be hyper - has complications too

Question 36

why are hypos importantb

Answer 36

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

Question 37

who is at risk of a ypoglycaemia \*

Answer 37

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

Question 38

when are hypoglycaemias more likely to occur \*

Answer 38

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

Question 39

why do hypos occur \*

Answer 39

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

Question 40

what are the signs and symptoms of hypoglycaemia due to increased autonomic activation \*

Answer 40

palpitations - tachycardia tremor sweating pallor/cold extremities anxiety

Question 41

what are the signs and symptoms of hypoglycaemia due to impaired CNS function \*

Answer 41

drowsiness confusion altered behhaviour focal neurology coma

Question 42

how do you treat hypoglycaemia \*

Answer 42

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

Question 43

how do you prevent hypos \*

Answer 43

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

Question 44

what is the scheme for t1dm diet management

Answer 44

DAFNE dose adjustment for normal eating provide you wit skills to estimate te right level of carbohydrate in each meal