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