1 - diabetes and its treatment Flashcards
negative consequences of diabetes
decreases life expectancy
contributes to kidney failure and CV diseases (MI and stroke)
diabetes mellitus type 1
hyperglycemia due to insufficient insulin secretion by the pancreas
relative percentages of people with T1 or T2 diabetes
10% of people with diabetes are Type 1
90% are T2
monogenic causes of diabetes
single gene defects of beta cells
MODY
maturity onset diabetes of the young
types of monogenic causes of diabetes
MODY (autosomal dominant gene mutation) neonatal diabetes (e.g. mutation in K+ATP channel)
properties of people with T2 diabetes
often older, overweight, commonly genetic cause
thirsty
polyuria
tiredness
lifestyle treatment for T2 diabetes
better diet
more exercise
pharmaceutical treatment for T2 diabetes
drugs to improve insulin sensitivity
e.g. metformin
drugs to stimulate insulin secretion
e.g. GLP-1 agonist
drugs to promote glucose excretion via kidneys
type 2 diabetes
long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin
type 1 diabetes
autoimmune destruction of insulin-producing pancreatic beta cells
signs of T1 diabetes
presence of autoantibodies and autoreactive T cells
total loss of beta cells within an islet
alpha cells remain intact
targets of autoreactive T cells in T1 diabetes
islet cells or their antigenic constituents
properties of people suffering from type 1 diabetes
young
rapid onset
thin/underweight at diagnosis
treatment of T1 diabetes
insulin replacement therapy
- injections or pump
monitoring of blood glucose
carbohydrate counting
transplantation of pancreas/islets
biomarkers for diabetes
HbA1c
anti-GAD
serum c-peptide
HbA1c testing
long-term –> tests average blood glucose over last 2-3 months
high HbA1c –> too much blood glucose
normal range for diabetes = 48 mmol/mol
who gets their HbA1c tested
patients that know they have diabetes already
what is HbA1c
Haemaglobin A1c
(glycated haemaglobin)
secreted when glucose builds up and sticks to blood vessels
anti-GAD as a diagnostic test
presence of anti-GAD identifies someone with T1 diabetes
–> suggestive of autoimmunity
blood test (from the arm) measuring whether the body is producing antibodies targeted to destroy its own GAD cells
what is GAD
glutamic acid decarboxylase enzyme
acts as an autoantigen –> stimulates antibodies to be released
which test determines which type of diabetes someone has
anti-GAD blood test
serum c-peptide test
what does serum c-peptide test for
shows how well the body is making insulin
how is serum c-peptide tested
blood or urine sample taken
what is c-peptide
released by beta cells when they make insulin
proinsulin + c-peptide = insulin
why is c-peptide a good biomarker for insulin production
C-peptide and insulin are present in pancreatic beta cells in equal amounts
C-peptide remains in your blood for approximately 5 times as long as insulin, and is therefore present in your blood at approximately 5 times the concentration
normal serum c-peptide range
0.5-2.0 ng/ml
what c-peptide results would indicate T1 diabetes
low serum c-peptide levels and high blood glucose
what c-peptide results would indicate T2 diabetes
high serum c-peptide levels and low blood glucose levels
most common mutation causing MODY
glucokinase mutation
MODY 2
alternative mutation causing MODY
HNFa mutation
(hepatocyte nuclear factor)
(MODY 1 and 3)
which type of diabetes is associated with insulin resistance
type 2
method and advantages of most common method of insulin delivery
insulin pen
insulin injected into subcutaneous tissue
little pain, easy, accurate therefore good for kids
disadvantages of insulin pen
exPENsive
not all insulin types available
alternative methods of insulin delivery
implantable insulin pump
external insulin pump
‘smart insulin’
insulin inhaler
methods of blood glucose monitoring
finger pricks (most common)
non-invasive monitoring (measures interstitial fluid)
flash glucose monitor (scan small white disk)
continuous glucose monitor
what is an artificial pancreas
system that measures blood sugar levels using a continuous glucose monitor (CGM)
transmits information to an insulin pump that calculates and releases the required amount of insulin into the body
benefits and disadvantages of artificial pancreas
no immunosuppressants required
little risk of infection
hard to connect glucose monitor to insulin pump
2 methods of beta cell replacement therapy
regeneration of remaining beta cells
islet transplants
process of regeneration of beta cells
some T1 diabetes patients still have detectable levels of c-peptide
chemicals can be used to enhance proliferation of beta cells
(transdifferentiation)
advantages and disadvantages of islet transplants
+
effective treatment –>reduces hypoglycaemic events
-
potential immune rejection
injecting islets into the liver can cause clots
insulin dependence may not last that long –> requires repeats
what is iPS cell treatment
induced pluripotent stem cell treatment
reverts cells back to stem cells so specialised cells can then be derived from them
advantages and disadvantages of iPS cell treatments
+
don’t need an embryo
fewer ethical issues
-
expensive
what is ES cell-based generation
embryonic stem cell-based generation
hijacking normally occurring differentiation pathways and replicating them in culture to produce specific specialised cells
how does ES cell-based generation work
replicate differentiation pathways of embryo from endoderm stage into mature pancreatic tissue
transcription factors change at every stage of differentiation therefore can be used as markers of specific stage
disadvantages of embryonic stem cell-based generation
difficult to generate fully functional cells in vivo
ethical issues from source of cells
transdifferentiation in mice
inject specific transcription factors to convert liver cells to beta cells or alpha cells to beta cells
importance of changing properties of insulin
changes the rate of absorption
properties of naturally occurring insulin
stored in the pancreas in tetramer crystals
tetramers broken up into monomers
rapid acting insulin
usually taken straight before a meal
peaks after 1 hour
often used with long-acting insulin
short-acting insulin
taken 30 mins before a meal
peaks after 2-3 hours
often used with long-acting insulin
intermediate acting insulin
covers glucose elevations when rapid-acting stops working
peaks after 4-12 hours
long-acting insulin
sustained basal insulin rate throughout day
can lower glucose levels for 24 hours
taken before bed
artificial pancreas is an example of …
a closed loop insulin delivery system
where does the artificial pancreas get its name?
it monitors and adjusts insulin levels just as the pancreas does in people without diabetes.
evidence that the artificial pancreas is effective
People using the system spent 14% more time with their glucose levels in the ideal range, compared to people using standard insulin therapy
They also had lower average overnight blood glucose levels without increasing hypos.
