Type 1 Diabetes Mellitus

Question 1

how is type 1 diabetes excluded?

Answer 1

antibodies
c-peptide
T1 genetic risk score

Question 2

what is GAD?

Answer 2

glutamic acid decarboxylase - pancreatic autoantibody

2.5% of normal population are GAD +ve through so doesn’t necessarily mean you have T1 diabetes

Question 3

what is C-peptide?

Answer 3

an easy confirmatory test for T1DM after 3 years - usually low in T1DM
usually present at time of diagnosis
can do fasting and non-fasting

Question 4

what negative tests result in a 5% chance of T1DM?

Answer 4

GAD, IA-2 and ZnT8 are negative

Question 5

what is it?

Answer 5

a state of absolute insulin deficiency, probably due to an environmental trigger in a genetically susceptible person, involves an auto-immune process that affects pancreatic beta-cells with varying degree of severity

Question 6

what is the genetic correlation?

Answer 6

HLA genes - represents 50% of family risk of T1DM

95% of people diagnosed with T1DM under 30 have either (DR3-DQU/DR4-DQ8) genotype or both

Question 7

Who gets it?

Answer 7

genetic link 
infection 
vit D deficiency 
puberty and stress can accerlerate
autoantibodies

Question 8

autoantibodies seen in T1DM

Answer 8

GAD 65Ab - antigen = glutamic acid decarboxylase, function = GABA production, increases with age
1A-2Ab - antigen = islet antigen 2, decreases with age in males
IAA - antigen = insulin, function = regulates glucose better in children?
ZnT8Ab - antigen = ZnT8 transporter, function in beta cells, better in the older?

Question 9

how is normal insulin secreted?

Answer 9

biphasic secretion in response to a meal
1. rapid phase of pre-formed insulin lasts 5 to 10 mins
2. slow phase over 1 to 2 hours
insulin secreted into portal vein and secretion continues in the fasted rate of 0.25 to 1.5 units/insulin/hr

Question 10

what autoimmune conditions are associated with it?

Answer 10

relatively common:
pernicious anaemia 
Addison's disease 
IgA deficiency
vitiligo 
primary hypogonadism 
primary hypothyroidism 
coeliac disease 
Cystic Fibrosis
very rare - auto-immune polyglandular syndromes, IPEX syndrome

Question 11

types of insulin

Answer 11

rapid-acting analogue e.g. Humalog, NovoRapid
Short-acting e.g. Humulin S, Insuman Rapid
Intermediate acting e.g. Humulin I, Insuman Basal
Long acting analogue e.g. lantus
Rapid acting analogue-intermediate mixture - Humalog Mix 25/Mix 50 or NovoMix 30
short acting-intermediate mixture - Humulin M3

Question 12

how is insulin delivered?

Answer 12

there are a variety of insulin delivery systems 
pens - disposable or with refillable cartridges 
insulin pump (more modern)

Question 13

aims of T1DM therapy

Answer 13

prevent hyperglycaemia
avoid hypoglycaemia
reduce chronic complications

Question 14

signs and symptoms of hyperglycaemia

Answer 14

thirst 
tiredness 
blurred vision 
weight loss 
polyuria 
nocturia 
fungal infections 
moot state 
can affect cognitive function (information processing and working memory)
potential risk of diabetic ketoacidosis

Question 15

signs and symptoms of hypoglycaemia

Answer 15

pallor 
sweating 
tremor 
palpitations 
confusion 
nausea
hunger 
can affect cognitive functions (tense-tiredness, information processing, working memory, coma)

Question 16

what is normal glucose/ insulin physiology?

Answer 16

insulin is secreted at a low basal rate which accounts for about 50% of insulin produced
post-prandial insulin is secreted in relation to post-meal glucose
this is the ultimate aim of trying to achieve insulin replacement therapy

Question 17

why is insulin therapy not as good as the real thing?

Answer 17

exogenous will always never be as good as endogenous insulin because of individual variations - absorption, timing and dose of insulin, condition of injection sites etc.

Question 18

what are the prandial insulins?

Answer 18

insulin analogues

soluble insulin

Question 19

what are basal insulins?

Answer 19

isophane ‘basal’ insulins

analogue basal insulins

Question 20

what does the basal bolus insulin regimen aim to do?

Answer 20

to mimic normal endogenous insulin production so is considered the best regime - rapid acting insulin is given before each meal and then long acting insulin before bed

Question 21

BD regimen

Answer 21

insulin is given twice a day
it’s less flexible
given in the morning and the evening

Question 22

OD regimen

Answer 22

insulin given once a day before bed

Question 23

what parent has a greater likelihood of passing on T1DM?

Answer 23

children are 3x more likely to develop diabetes than if their mother has it

Question 24

how is it managed?

Answer 24

most people get MDI or CSII

most people with T1DM should use insulin analogues to reduce hypoglycaemia risk

Question 25

what insulin are adults given?

Answer 25

regular human/rapid-acting analogues - if they are experiencing severe/nocturnal hypoglycaemia and are using an intensified insulin regimen - basal insulin analogues

Question 26

what insulin are children and adolescents given?

Answer 26

insulin analogues (rapid acting or basal) or regular human insulin and NPH preparations or an appropriate combo

Question 27

how is metabolic control evaluated?

Answer 27

home blood glucose monitoring (SBGM) glycated haemoglobin (HbA1C) flash glucose monitoring freestyle libre continuous glucose monitor (CMS) BGM - very important but only provides a snap shot at any given moment

Question 28

what are the HbA1C targets

Answer 28

first 10 years = 48 mmol/mol | as they get older = 53/58 mmol/mol

Question 29

what is the characteristics of normal physiological (pancreatic) insulin

Answer 29

secreted directly into the portal bloodstream rapidly prevents post-meal hyperglycaemia rapidly cleared

Question 30

what are the characteristics of insulin therapy (injection/pump)

Answer 30

injection into subcutaneous tissue peaks too slow to precent post-meal hyperglycaemic spike slow clearance

Question 31

what factors affect insulin absorption/action

Answer 31

``` temperature injection site injection depth exercise check needle - may need new one ```

Question 32

what are important safety measures in insulin prescription

Answer 32

make sure not to use abbreviations because they all have similar names and there is danger in the unit symbols being mistaken for numbers

Question 33

principles of insulin dose adjustment

Answer 33

review glycaemic control adjust routine insulin proactively to optimise glycaemic control - be aware that reactive insulin adjustment can cause hypoglycaemia adjust insulin dose prescribed before the problem DON'T omit insulin if hypoglycaemic, treat hypo and administer insulin as usual

Question 34

non-insulin adjunct therapy in T1DM

Answer 34

metformin leptin GLP-1 SGLT2i

Question 35

how should insulin never be administered

Answer 35

IV syringe

Question 36

what are the rules for insulin for short fast/minor surgery?

Answer 36

IV insulin is not necessary if a rapid recovery is expected and the patient is expected to eat following the procedure avoid glucose infusions if possible monitor blood glucose there is risk of hypoglycaemia in people prescribed oral hypoglycaemic agents and insulin the Diabetes team can offer advice