type 1 diabetes Flashcards
what is the pathophysiology of type 1 diabetes
autoimmune condition in which insulin producing b-cells of pancreas are attacked and destroyed by the immune system.
result of pathology in type 1 diabetes biochemiclaly and clinically
partial or complete defficiency of insulin production leading to hyperglycemia which requires life long treatment
(ALSO see diagram on ppt slide 7) - what diabetes classifications did WHO verify in 2019? (5)
type 1
type 2
other
unclassified
during pregnanct
what is monogenic diabetes?
some different types of diabetes in the “other” category that are all caused by a specific gene mutation (caused by one gene: monogenic).
so the genetic component is a direct cause rather than predisposition as in other types.
what are some examples of monogenic diabetes?
MODY (maturity onset diabetes of he young) mitochondrial diabetes
what type of diabates (1/ 2) can monogenic diabetes phenotypically present as? (what is the common misconception?)
can be both, in the past many people think mainly of type 2
after what kind of condition can diabetes commonly follow?
pancreatic damage or other endocrine disease :ex. cystic fibrosis
in what types of diabetes can you get diabetic ketoacidosis? and common misconception
both 1 and 2 (misconception: only in 1 )
what age can t2d prenet in?
most common in older but can be childhood too
can autoimmune diabetes present in later life?
YES latent autoimmune Diabetes in adults LADA, in every decade of life
what is a difficulty experts face considering that type 1 can develop later in adults?
clinicians are faced with a challenge trying to differentiate adult onset type 1 diabetes form the much large number of cases of type 2
what are the stages of development of type 1 diabetes? (look at graph slide 10 b-cell mass over age)
b cell mass normal:
1) genetic predisposition
2) potential precipitating event
b cell mass declining:
3) overt immunological abnormalities (ex. self antibodies present ect) - 1 autoantibody
normal insulin release
> or= 2 autoantibodies:
4) progressive loss of insulin release
glucose normal
5) overt diabetes
c- peptide present (representing: some self insulin )
6) no c peptide present
which component(s) of the immune system are defective in type 1 diabetes?
both
explain firefly process of autoimmunity in type 1 d (check diagram slide 13)
1) APC presents auto anitgen to CD4
2) CD4 T cell activates (b cell and ) CD8 t cell
3) cd8 goes to islets and starts lysing beta cells in pancreas expressing auto antigen
4) this is exacerbrated by inflammatory cytokines (released by the lysed cells?)
this is also supported by defective (wrongly trained from thymus) T reg cells that fail to supress autoimmunity
do all type 1 diabetes patients eventually lose all their insulin production? does that matter in terms of treatment?
Some people with type 1 diabetes continue to produce small amounts of insulin
Not enough to negate the need for insulin therapy
however Even this little is good, in research they were less likely to have complicaitons and less likely to have low blood sigars after treat ect
what us the gene that detemrones siceptibility to type 1 diabetes?
HLA-DR gene
what allleles are significant risk?
DR3 DR4
WHAT ALLeles only have slight risk?
DR1, DR5, DR8 (neutral/ slight risk)
what alleles have different effects on specific ethnic groups?
DR9 (Risk in Chinese, Japanese, Korean descent)
DR7 (Protective. Risk in African descent)
what are 4 categories of functions of loci that have been identified on people with t1d in gneome wide associations?
insulin production and metabolism,
immunity
b cell apoptosis protection
unknown function
what are some factors that have been associated as evironmental triggers of t1d.
-Enteroviral infections
-Cow’s milk protein exposure
-Seasonal variation: less patients showing up in summer
-Changes in microbiota
at what stage of t1d are pancreatic autoantibodies most apparent in sera of patients? (why?: not in bullets but key for understanding)
at diagnosis, because down the line the more the b cells are destroyed over years., there isnt anything to attack any more really so antibodies decrease
what does NICE recommend we use pancreatic autoantibody levels for? what specific antibodies/ substances?
diagnosis,
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GAD-65) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2)
Zinc-transporter 8 (ZnT8)
symptoms of t1d
4ts:
thirsty
thinner
tired
toilet polyuria and nocturia
blurring of vision
reccurent infections eg thrush
signs of t1d (dont come holding some gun kon)
dehydration
cachexia (muscle wasting)
hyperventilation
smell of ketones
glycosuria
ketonuria
why may you have cachexia and weigh loss (one of the mechs) in t1d? (muscle wasting
because the body cant use glucose for energy so it uses stored fat (lipolysis resulting in nefa and gly) and protein from muscles (proteinolysis gives aas) also glycolysis from liver
why may you hyperventilate in t1d?
if you have ketoacidosis, blood body tries to excrete as much co2 as possible by hyperventilating to make the blood less acidic (co2- carbonic acid in blood- acidic blood)
what are the main components to make a t1d diagnosis and what are some aditional less essential ones?
1) clinical features
2) presence of ketones
potentially also pancreatic autoantibodies and c peptide
what does DKA stand for
diabetic ketoacidosis
what are 3 ketone bodies
acetyl coA
acetoacetate
acetone + 3 OH-B
in what organ/cell does the conversion of fatty acyl coa to ketone bodies happen?
in liver- hepatocyte
which pancreatic hormone inhibits and which prommotes acyl coa to ketone body conv?
insulin inhibits
glucagon promotes
what is NEFA and what is fatty acyl coa
non esterified fatty acid (means not bound to acyl group- means free fatty acid), and fatty acil co ais bound…
What is the role of NEFA in ketogenesis?
NEFA are another substrate (other than glucagon) that can be converted to ketone bodies
what are the aims of type 1 diabetes treatment?
(glucose, insulin, ketones, complications)
prevent acute metabolic decompensation (crises such as ketoacidosis ect.)
restore a close to physiological insulin profile
maintain glucose levels without excessive hypoglycaemia
prevent microvascular (eyes) and macrovascular complications (ischaemic heart disease for ex.)
complications of hyperglycemia acute
diabetic ketoacidosis
complications of hyperglycaemia chronic 2 types and examples
macrovascular: ischaemic heart disease, cerebrovascular disease, peripheral vascular disease
and microvascular : retinopathy, neuropathy, nephropathy
what are the different methods of management of type 1 diabetes and what type of condition is diabetes considered in terms of management?
-self-managed condition
- insulin treatment
- dietary support / structured educations
- technology (the new glu level monitor)
- transplantation (pump)
what is a physiological insulin profile (see slide 25)
insulin is never completely suppressed, there is basal insulin which has a flat profile
prandial (post food) peak has 2 phases ( first is high peak, then lower peak then drops towards basal)
In treatment, how is this pattern of insulin replicated?
1) different types of insulin given for the different insulin levels (prandial and basal) - short- quick acting/ long acting: basal (theres also an intermediate acting type)
2) different frequencies of administration for each type
what is short acting insulin (molecular level) and examples of brands?
either exact molecular replicate of human insulin (actrapid)
or insulin analogue (lispro, aspart, glulisine)
what is long acting insulin (molecular level)+ brands
either insulin bound to zinc or protamine (neutral protamine hagedorn (NPH)
OR
insulin analogue (glargine, determir, degludec)
what is the typical basal bolus regime
3/d prandial: short acting after each meal
1/ d long acitng OR 2/ day if intermediate acting is used
what does the insulin pump do (doses/ freq and method) and what do you have to do?
general:
insulin delivered in subcutaneous space
for bolus insulin:
1) you need to actively set it for when you have meals
2) pump can do continuous delivery (meaning not just injection at once, it can give the dose slowly over a few minutes/ hour?) of short acting insulin analogue
for long acting:
1) programme the device to deliver fixed units/ hour throughout the day (basal)
what are some benefits of the insulin pump and what is the single greatest benefit
variable basal rates : biggest benefit
extended boluses
greater flexibility
what are the 3 principles of dietary advice for people with t1d?
1) dose adjustment for carbohydrate content food
2) all patients should recieve training for cRBOHDRATE COUNTING
3) substitution of refined carbohydrate containing foods where possible
nice guidlines dor type 1 diabetes (training patients related) 3 points
All people with type 1 diabetes should be offered a Structured Education Programme
e.g. DAFNE (dose adjustment for normal eating) but many others
5 day course on skills and training in self-management
what is a hybrid closed loop system
implant of 2 devices that commnicate:
1) real time continuous glucose sensor (new thing)
2) glucose pump: a) will use an algorithm to calc insulin req from gluc level
Is hybrid closed loop system available on NHS?
yes
where do you get the cells for a islet cell transplant?
1) isolate human islets from pancreas of deceased donor
where do you transplant the derived islet cells form donor?
Transplant into hepatic portal vein
what other action is required for islet cell transplant to work
life long immunosupression
what procedure increases the survival of pancreas graft?
a simultaneous pancreas and kidney transplant:
transplanting the pancreas graft ALONG WITH KIDNEYs (we dont know why exactly)
again requires life long immunosupression
what is the aim/ benefits of transplants?
try to restore physiological insulin production to the extent that insulin can be stopped
Even if incomplete, often results in better control
limitations fo transplants
Limitations: availability of donors, complications of life-long immunosuppression
how do people without the continuous glucose monitoring device monitor glucose levels?
with capillary (finger prick) blood glucose monitoring
what does HBA1c reflect and why so?
last 3 months of glycaemia
bc thats the lifepsan of a rbc and HBA1c is basically glycated haemoglobin
what is a disadvanatge of HbA1c?
-Biased to the 30 days preceding measurement
means that if reflects more the glu levels in the past 30 days bc old glycated rbcs are starting to get replaced by new rbcs
what is the difference between glycosylation and glycation and which process ois relevant to HbA1c
glycosylation is enzymatic- glycation is non enzymatic so its a linear chemical reaction
relevant is glycation
what is the first step of the glycation reactions of hb? is it fats or slow ? is it an equillibrium?
N-terminal valine residue b-chain and glucose —–> <—– (equilibrium) Schiff base
its fast- takes hours
what is the second step of the glycation reactions of hb? is it fats or slow ? is it an equillibrium?
slow-takes days
Schiff base—-> Amadori product (HbA1c)
is this glycation a reversible reaction?
no
other reasons why HBa1c is not a perfect measurement
(slide 36)
what is used to guide insulin doses?
self-monitoring of blood glucose results at home and HbA1c results every 3-4 months
what are acute complications from type 1 diabetes?
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
what are acute complications of t1d
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
when is ketoacidosis more common? (type of diabetes and phase in disease)
new onset type 1 diabetes
(but can occur in any type)
what are some triggers of ketoacidosis
Acute illness
Missed insulin doses
Inadequate insulin doses
is ketoacidosis life threatening?
yes
Diabetic ketoacidosis diagnosis. (4 things)
pH <7.3,
ketones increased (urine or capillary blood),
HCO3- <15 mmol/L and
glucose >11 mmol/L
how common (not percentage expected just describe) is hypoglycaemia in type 1 diab patients?
To some extent an inevitable feature of the self-management of type 1 diabetes bc: Lost normal physiology and homeostasis’
numerical def of hypoglycaemia
(variable) <3.6 mmol/L
what is meant by severe hypoglycaemia?
any event requiring 3rd party assistance (this just means you lose ability to self manage, doesn’t mean you have too low level of glu-
when can hypoglycaemia become a problem>?
Excessive frequency
Impaired awareness (unable to detect low blood glucose) (lack of adrenergic symptoms ) (i think this is severe hypoglycaemia)
Nocturnal hypoglycaemia (this is also severe)
Recurrent severe hypoglycaemia
risks of hypoglycaemia
Seizure / coma/ death (dead in bed)
Impacts on emotional well-being
Impacts on driving
Impacts on day to day function
Impacts on cognition
role of HbA1c in hypoglycaemia identifiction?
HbA1c itslef may not be helpful
what are some risk factors for hypoglycaemia
Exercise
Missed meals
Inappropriate insulin regime
Alcohol intake
Lower HbA1c
Lack of training around dose-adjustment for meals
strategie sto support problematic hypoglycaemia
Indication for insulin-pump therapy (CSII)
May try different insulin analogues
Revisit carbohydrate counting / structured education
Behavioral psychology support
Transplantation
acute management of hypoglycaemia if alert and orientated
Oral Carbohydrates
Rapid acting;
juice / sweets
Longer acting;
sandwich
acute management of hypoglycaemia: Drowsy / confused but swallow intact
Buccal glucose
e.g. Hypostop / glucogel
Complex carbohydrate
acute management of hypoglycaemia:Unconscious or concerned about swallow
IV access
20% glucose IV
20% glucose IV
if Deteriorating / refractory /insulin induced /difficult IV access?
consider IM /SC 1mg Glucagon
is giving cake a good way to spike sigars?
no, if has fat, slows doen glu bsorption, you want pure sugar like choc, sweets ect
why important language matters
What you tell them they think of that after bc they carry the diseas ewith them, so its better to use motivating language
this matter sbc its a self managed disease, so psych infl how well they manage themselves
phrases to avoid
poor control’ ‘diabetes sufferer’
‘not coping’ ‘poor compliance’
‘how’s your control’
‘they’re diabetic’
‘you can’t eat that’
more motivaitn emowering stuff
person living with diabetes’
‘it sounds like your diabetes has been challenging to manage recently’
‘what are your thoughts on your recent glucose levels’
‘let’s talk through different options and see what suits you’
