Endo 16: Type 1 diabetes

Question 1

T/f DKA only occurs in T1DM

Answer 1

F, also feature of T2DM

Question 2

t/f monogenic diabetes is only ever t1dm

Answer 2

F, Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)

Question 3

Patietns presenting with T1DM in adult life may have what

Answer 3

latent autoimmune diabetes in adults (LADA)

Question 4

Basic mechanism of type 1 and type 2

Answer 4

1:
Environmenta trigger+ genetics –> autoimmune destruction of islet cells –> insulin deficiency –> hyperglycaemia

2:
Genetics+obesity –> insulin resistance –> b cell failure (due to long term hyperglycaemia, so need insulin eventually) –> hyperglycaemia

Question 5

Components of type 1 diabetes cause

Answer 5

Immune dysregulation, environmental triggers and regulators

Question 6

Why is there a relapsing/remitting stage

Answer 6

Increase in effector T cells is followed by increase in regulatory T cells, over time effector T cells increases to a greater extent than the regulatory T cells, at which point hyperglycaemia occurs ….

READ: Model for type 1 diabetes as a relapsing-remitting disease.

Question 7

What is the honey moon phase

Answer 7

beta cells temporarily recover then switch off

Question 8

Which disease can occur due to immune basis of T1DM

Answer 8

B12 deficiency, ONE MORE
Hashimotos
Addison’s disease

Question 9

Ideas of novel treatment

Answer 9

Immune modulation offers the possibility of novel treatments

Question 10

What can be seen on histology with t1dm

Answer 10

Inflammation in islets of langerhans

Question 11

Where is HLA located

Answer 11

Chr 6

Question 12

Which HLA-DR allele increases risk of T1DM

Answer 12

DR3/DR4

Increases likelihood of immune cell interaction with these antigens

Question 13

Incidence of DKA occurring

Answer 13

Less in summer times compared to other times of year (possible more infection in winter?)

Question 14

Which markers can confirm type 1 DM (not always needed)

Answer 14

Islet cell antibodies (ICA)- grp O human pancreas

Glutamic acid decarboxylase (GADA) – widespread nuerotransmitter

Insulin antibodies (IAA)

Insulinoma-associated-2 autoantibodies (IA-2A)-receptor like family

but doesn’t effect treatment

Question 15

T1DM presentation SYMPTOMS

Answer 15

polyuria 
nocturia
polydipsia 
blurring of vision
‘thrush’ 
weight loss
fatigue

Question 16

T1DM SIGNS

Answer 16

dehydration 
cachexia
hyperventilation (due to metabolic acidosis, to blow off CO2.... kussmauls breathing)
smell of ketones
glycosuria 
ketonuria

Question 17

Metabolic effects of insulin

Answer 17

Glucose regulated through liver, muscle and fat cells

3 checks to prevent hyperglycaemia:

1. Insulin prevents gluose from getting out of the limit
2. Unsluin causes glucose to get into muscle
3. Prevents fat from getting out of adipose cells as glycerol and used in gluconeogenesis

Question 18

How are the ketone bodies produced

Answer 18

Breakdown of adipocytes leads to glycerol (–>liver for gluconeogenesis)

AND

fatty acids (–>liver making ketones)

Question 19

Are ketones a good wa to determine insulin deficiency

Answer 19

Y, Ketones define insulin deficiency

Question 20

Aims of t1m treatment

Answer 20

Reduce mortality

Prevent long term complications (micro and macrovascular issues)

- retinopathy
- nephropathy
- neuropathy
- vascular disease

Question 21

What is recommended in t1dm for diet (less important than t2dm, but sitll)

Answer 21

reduce calories as fat
reduce calories as refined carbohydrate
increase calories as complex carbohydrate
increase soluble fibre

balanced distribution of food over course of day with regular meals and snacks

Question 22

T/f insulin is only produced after meals

Answer 22

F: there is a basal amount of insulin, makes up 50% of what you need

Question 23

What does insulin treatment involve

Answer 23

With meals
Short acting
Human insulin
Insulin analogue (Lispro, Aspart, Glulisine)

+

Background
Long acting
Non-c bound to zinc or protamine
Insulin analogue (Glargine, Determir, Degludec)

Question 24

What kind of insulin is used

Answer 24

Genetic engineering to alter absorption,

distribution, metabolism and excretion

Question 25

Slide 27

Answer 25

Short acting insulin after meals and then background insulin (blue) works for 14 houra

Question 26

Slide 28

Answer 26

if 3 short acting ones, then give 1 background insulin per day Point is that you tailor regime to how often they eat, and how much they eat each tim

Question 27

When is insulin pump given

Answer 27

Often when pens don't work (i.e. they keep getting HYPOS)

Question 28

T/F insulin pump gives only short acting insulu

Answer 28

F... it's background, then they can inform it when there are food bolus

Question 29

When are islet cells transplanted

Answer 29

if they keep getting hypos with pens and pumps.... islet cells injected into portal system and produces insulin... must give suppressants

Question 30

How can the success of treatment be measured

Answer 30

Capillary monitorying/ hba1c

Question 31

What is capillary monitorig

Answer 31

tests glucose levels... can give electroic device which can measure the glucose pver long period of time which you can use to inform the treatment regime

Question 32

What is hba1c

Answer 32

Relies on RBCs.. glucsose molecules attach to Hb... RBC half life is 120 days, so can measure glucose over 3 month period

Question 33

When is hba1c not relaible

Answer 33

Haemolysis, or Fe deficiency anaemia

Question 34

Why is Hba1c useful

Answer 34

Forms ideal measure of long term glycaemic control and has been shown to be related to risk of complications. Furthermore lowering HbA1c associated lower risk of complication particularly microvascular complication

Question 35

What is ketosis

Answer 35

rapid decompensation of type 1 diabetes.... involving hyperglycaemia nad metabolic acidosis

Question 36

Metabolic disturbances in ketoacidosis

Answer 36

hyperglycaemia - reduced tissue glucose utilisation - increased hepatic glucose production metabolic acidosis - circulating acetoacetate & hydroxybutyrate - osmotic dehydration and poor tissue perfusion

Question 37

Why do diabetics get hypogylcaemia

Answer 37

occasional hypos inevitable as a result of treating diabetes major cause of anxiety in patients & families source of major misconceptions in medi

Question 38

Define hypoglycaemia vs sever hypoglycaemia

Answer 38

hypoglycaemia - plasma glucose of < 3.6 mmol / l | severe hypoglycaemia - any hypo requiring help of another person to treat

Question 39

What happebs at glucose: <3mmol/l <2mmol/l

Answer 39

most mental processes impaired at <3 mmol/l consciousness impaired at <2 mmol/l severe hypoglycaemia may contribute to arrhythmia and sudden death

Question 40

Long terms effects of hypoglycaemia

Answer 40

may have long-term effects on the brain | recurrent hypos result in loss of warnings= HYPOGLYCAEMIC UNAWARENESS

Question 41

Who is at risk of hypo

Answer 41

- main risk factor is quality of glycaemic control | - more frequent in patients with low HbA1c (i.e. well controlld)

Question 42

When does hypo occur

Answer 42

can occur at anytime but often a clear pattern - pre-lunch hypos common - nocturnal hypos very common and often not recognised

Question 43

Why do hypos occur

Answer 43

``` unaccustomed exercise missed meals inadequate snacks alcohol inappropriate insulin regime ```

Question 44

Symptos due to hypoglycaemia

Answer 44

1. Due to increased autonomic activation ``` palpitations (tachycardia) tremor sweating pallor / cold extremities anxiety ``` 2. Due to impaired CNS function ``` drowsiness confusion altered behaviour focal neurology coma ```

Question 45

Hypolycaemia treamtent

Answer 45

ORAL feed the patient! glucose - rapidly absorbed as solution or tablets complex CHO - to maintain blood glucose after initial treatment ``` PARENTERAL give if consciousness impaired IV dextrose e.g 10% glucose infusion 1mg Glucagon IM avoid concentrated solutions if possible (e.g 50% glucose) ```

Question 46

Why may glucagon not be given (it can usualyl be but why not)

Answer 46

Glucagon is reliant on there being adequate store of sugar in the liver... if they have been really unwell may not work

Question 47

Give names of 2 short acting and 2 long acting insulin analogues

Answer 47

short: Lispro, Aspart, Glulisine) long: (Glargine, Determir, Degludec)