Diabetes management and therapeutics Type 1 Flashcards
type 1 diabetes also know as insulin depends diabetes mellitus is what
autoimmune destruction on pancreatic beta cells resulting in less insulin produced so insulin insufficient
the body destroys the beta cells so no insulin produced and more glucose in the blood as glucose cannot move into the cells causing high blood sugar levels
what age group often get type 1
younger
common presentation of type
polyuria
polydipsia
unintentional weight loss
and/or DKA
main treatment for type 1 diabetes
insulin injection
what are incretins
regulate the amount of insulin that is secreted after eating.
what is the incretin effect
The incretin effect describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals.
what is the structure of insulin
peptide chain ( A and B ) connected bu 2 disulphide bridges
what is the structure of glucagon
one long polypeptide chain like 27 amino acts
genes coding insulin are transcribed to mRNA in the nucleus. formation offinsulin starts with preproinsulin in ribosome of rough er it is then cleaved to proinsulin. this is transported to the Golgi and packaged into secretory granules in equal amounts of two substances what are they
c-peptide
insulin
what is c peptide used for
marker for endogenous insulin production
insulin is aggregated into hexameters with zine
but dissociate into what
active monomer form
how can we give insulin dose
not orally as insulin is inactivated by gastrointestinal enzymes so cannot be given orally.
solution use a parenteral route such as IV ( DKA and surgery) and SC ( injection in abdomen or thigh
how do you overcome the problem of exogenous insulin reflecting endogenous insulin release. ( i.e. the basal release and the peaks)
use insulin preparations with different duration of action
use intermediate and long acting insulin for basal levels and rapid/ shot acting insulin before meals
what type of insulin do you use before meals
rapid or short acting
what insulin do you use to maintain basal levels
long or intermediate acting
half life of insulin
30mins
from rapid to long acting insulin what is the trend
longer duration of action
i.e. rapid is 2-4 hours
short 6-8, intermediate 11-18 and long 20-24
onset of action increases time
so rapid works in 15min, short 30-60min
intermediate and long are 1-2h
example of rapid acting insulin example
prevent them readily forming dimers or hexameters leading to faster absorption and fast onset and short duration
aspart ( analoge)
used to mimic insulin bolus that occurs with intake
example os short acting
regular insulin ( aka soluble) human insulin
used to mimic insulin bolus that occurs with intake
example of intermediate acting insulin
suspension of insulin with protamine so dissolve slowly and delayed absorption
NPH ( isophane insulin ) human insulin
used to mimic basal insulin
often mixed with short for biphasic regimes
example of long acting insulin
glargine or determir
analgoues
detemir adds fatty acid chain and increase hexameter formation and albumin binding so aid slower absorption and albumin dissociation
glargine adds 2 additional arginine residues and glycine replaces asparagine reducing solubility at physiological pH
human insulin I produced by recombinant DNA and uses sam aa as human insulin
insulin analogies are recombinant modifications of human insulin but invovle some AA changes - this allows for modifications of what
absorption , duration and or onset of action
what type of insulin is mixed with short acting for biphasic regimes
intermediate
when choosing a regime a basal level of insulin with insulin boluses prior to intake is best looking at factors such as age and lifestyle and preference
what regimes can you have
e
explain them all
what is first recommendation by NICE
multiple daily injection MDIs - long acting at breakfast an bedtime plus rapid acting before meals - first line recommendation by nice
biphasic ( mixed) - both short and intermediate in same twice daily before breakfast and evening meal - stable eating habits
continuosu SC insulin infusion CSII
CGM - continuous glucose monitors
nice recommends what as first line for Typ1
MDIs - long acting at bed and breakfast and rapid or short before meals - need go flexibility
what is best is stable activity and eating habits
biphasic - twice daily before break and evening meal
what is recommended if you ova recurrent hypoglycaemia with MDIs or presistant hyperglycaemia despite MDIs
CSII
delivered by subcutaneous insulin infusion pump
continuou basal insulin infusion and patent activated bolus doses at meals
connected to monitors to
what method would be best for someone who likes to examine trends and avoids wild glucose levels and alarms fro episodes
CGM - sensors inserted in subcutaneous tissue measures itnstitial glucose levels and transmitted to receiver
Suri is an 8-year-old girl who has been diagnosed with type 1 diabetes. She is an active girl who enjoys frequent snacking and playing with her friends. Suri is also a keen swimmer and a ballet dancer.
Which one of the following insulin regimens would be best for Suri?
Once daily regimen with a long or intermediate acting insulin analogue before bedtime
Twice daily regimen with a long-acting analogue before evening meal and short-acting soluble insulin 30 min before breakfast
Basal-bolus regimes that includes multiple injections to cover mealtimes and a long-acting insulin before bedtime
Twice daily regimen with biphasic insulin mixture
c
Maria is a 34-year-old female. She has been treated for type 1 diabetes since 15yrs of age. She has a consistent daily routine and regularly eats three meals a day. She currently has a multiple injection regimen but wants to reduce the number of injections she needs. Her last hypoglycaemic episode was 3 years ago.
Which one of the following insulin regimens would be best for Maria?
Start on an insulin pump
Use a once daily long-acting insulin regimen
Use a twice daily biphasic insulin regimen
Use a once daily biphasic insulin regimen
c
Andy, aged 14-years-old, was brought to A&E in a semi-conscious state and later admitted to the hospital as he was diagnosed with diabetic ketoacidosis. This was due to undiagnosed type 1 diabetes which resulted in a very high blood glucose, ketone bodies and acidosis.
Which one of the following is the best option for immediately controlling Andy’s blood glucose levels and subsequently suppressing ketone formation:
Single subcutaneous injection of soluble insulin
Intravenous infusion of soluble insulin
Single subcutaneous injection of rapid acting insulin analogue
Single subcutaneous injection of biphasic insulin
b
Ibrahim is a 20-year-old student with type 1 diabetes. He is currently on a daily multiple injection insulin regime consisting of a single long-acting insulin at breakfast and rapid-acting insulin prior to meals. However, Ibrahim experiences recurrent episodes of hypoglycaemia. He also has erratic eating patterns due to juggling his studies and part-time work.
Which one of the following insulin regimens would be best for Ibrahim?
Continuous basal infusion with patient activated boluses via an insulin pump
Twice daily injections of a biphasic preparation before his breakfast and evening meal
Single daily
subcutaneous injection of long-acting insulin at breakfast
Change rapid-acting insulin analogue to short-acting soluble insulin
A
Which one or more of the following factors are likely to increase the insulin dose required by a patient with type 1 diabetes?
Infection
Surgery
Reduced food intake
A course of steroids e.g. prednisolone
all of them but reduced food intake
what alternative treatment options are there
islet cell transplant
whole organ pancreas transplant
Reduced mortality rate compared to patients on the waiting list
Reduced risk of severe hypos
Potential insulin independence - more likely for pancreatic compared to islet transplant
BUT
Patients require lifelong immunosuppression
Graft survival approx. 80-88% at 1yr but 54% at 5yrs
Islet transplants require islets from more than one organ donor
Pancreatic transplant = large operation
who is eligible for treatment
patents who have unexpected episodes of dangerously low blood sugar levels despite good insulin control
patients with severe kidney disease regardless of cause may have simultaneous pancreas and kidney transplant
what is immunotherapy
Aims to prevent or delay the loss of functional beta cell mass
Many focus on antibodies targeting T effector cells
Example: Teplizumab
anti-CD3 monoclonal antibody
Shown some attenuation of loss of beta cell function
Phase II trial: 50% risk reduction of developing T1D in individuals at high risk (Herold et al, 2019)
Current Phase III involving children/adolescents with recently diagnosed T1D
stem cell replacement therapy
Aim to replace/supplement lost or dysfunctional beta cells
BUT
Stem cell derived beta cells may succumb to immune-mediated destruction
Potential solutions:
Immunosuppression but side effects
Encapsulating beta cells to protect them = research in early stages
