Diabetes management and therapeutics Type 1

Question 1

type 1 diabetes also know as insulin depends diabetes mellitus is what

Answer 1

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

Question 2

what age group often get type 1

Answer 2

younger

Question 3

common presentation of type

Answer 3

polyuria
polydipsia
unintentional weight loss
and/or DKA

Question 4

main treatment for type 1 diabetes

Answer 4

insulin injection

Question 5

what are incretins

Answer 5

regulate the amount of insulin that is secreted after eating.

Question 6

what is the incretin effect

Answer 6

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.

Question 7

what is the structure of insulin

Answer 7

peptide chain ( A and B ) connected bu 2 disulphide bridges

Question 8

what is the structure of glucagon

Answer 8

one long polypeptide chain like 27 amino acts

Question 9

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

Answer 9

c-peptide

insulin

Question 10

what is c peptide used for

Answer 10

marker for endogenous insulin production

Question 11

insulin is aggregated into hexameters with zine

but dissociate into what

Answer 11

active monomer form

Question 12

how can we give insulin dose

Answer 12

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

Question 13

how do you overcome the problem of exogenous insulin reflecting endogenous insulin release. ( i.e. the basal release and the peaks)

Answer 13

use insulin preparations with different duration of action

use intermediate and long acting insulin for basal levels and rapid/ shot acting insulin before meals

Question 14

what type of insulin do you use before meals

Answer 14

rapid or short acting

Question 15

what insulin do you use to maintain basal levels

Answer 15

long or intermediate acting

Question 16

half life of insulin

Answer 16

30mins

Question 17

from rapid to long acting insulin what is the trend

Answer 17

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

Question 18

example of rapid acting insulin example

prevent them readily forming dimers or hexameters leading to faster absorption and fast onset and short duration

Answer 18

aspart ( analoge)

used to mimic insulin bolus that occurs with intake

Question 19

example os short acting

Answer 19

regular insulin ( aka soluble) human insulin

used to mimic insulin bolus that occurs with intake

Question 20

example of intermediate acting insulin

suspension of insulin with protamine so dissolve slowly and delayed absorption

Answer 20

NPH ( isophane insulin ) human insulin

used to mimic basal insulin
often mixed with short for biphasic regimes

Question 21

example of long acting insulin

Answer 21

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

Question 22

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

Answer 22

absorption , duration and or onset of action

Question 23

what type of insulin is mixed with short acting for biphasic regimes

Answer 23

intermediate

Question 24

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

Answer 24

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

Question 25

nice recommends what as first line for Typ1

Answer 25

MDIs - long acting at bed and breakfast and rapid or short before meals - need go flexibility

Question 26

what is best is stable activity and eating habits

Answer 26

biphasic - twice daily before break and evening meal

Question 27

what is recommended if you ova recurrent hypoglycaemia with MDIs or presistant hyperglycaemia despite MDIs

Answer 27

CSII delivered by subcutaneous insulin infusion pump continuou basal insulin infusion and patent activated bolus doses at meals connected to monitors to

Question 28

what method would be best for someone who likes to examine trends and avoids wild glucose levels and alarms fro episodes

Answer 28

CGM - sensors inserted in subcutaneous tissue measures itnstitial glucose levels and transmitted to receiver

Question 29

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

Answer 29

c

Question 30

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

Answer 30

c

Question 31

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

Answer 31

b

Question 32

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

Answer 32

A

Question 33

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

Answer 33

all of them but reduced food intake

Question 34

what alternative treatment options are there

Answer 34

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

Question 35

who is eligible for treatment

Answer 35

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

Question 36

what is immunotherapy

Answer 36

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

Question 37

stem cell replacement therapy

Answer 37

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