Endo 16: Type 1 diabetes Flashcards
T/f DKA only occurs in T1DM
F, also feature of T2DM
t/f monogenic diabetes is only ever t1dm
F, Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
Patietns presenting with T1DM in adult life may have what
latent autoimmune diabetes in adults (LADA)
Basic mechanism of type 1 and type 2
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
Components of type 1 diabetes cause
Immune dysregulation, environmental triggers and regulators
Why is there a relapsing/remitting stage
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.
What is the honey moon phase
beta cells temporarily recover then switch off
Which disease can occur due to immune basis of T1DM
B12 deficiency, ONE MORE
Hashimotos
Addison’s disease
Ideas of novel treatment
Immune modulation offers the possibility of novel treatments
What can be seen on histology with t1dm
Inflammation in islets of langerhans
Where is HLA located
Chr 6
Which HLA-DR allele increases risk of T1DM
DR3/DR4
Increases likelihood of immune cell interaction with these antigens
Incidence of DKA occurring
Less in summer times compared to other times of year (possible more infection in winter?)
Which markers can confirm type 1 DM (not always needed)
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
T1DM presentation SYMPTOMS
polyuria nocturia polydipsia blurring of vision ‘thrush’ weight loss fatigue
T1DM SIGNS
dehydration cachexia hyperventilation (due to metabolic acidosis, to blow off CO2.... kussmauls breathing) smell of ketones glycosuria ketonuria
Metabolic effects of insulin
Glucose regulated through liver, muscle and fat cells
3 checks to prevent hyperglycaemia:
- Insulin prevents gluose from getting out of the limit
- Unsluin causes glucose to get into muscle
- Prevents fat from getting out of adipose cells as glycerol and used in gluconeogenesis
How are the ketone bodies produced
Breakdown of adipocytes leads to glycerol (–>liver for gluconeogenesis)
AND
fatty acids (–>liver making ketones)
Are ketones a good wa to determine insulin deficiency
Y, Ketones define insulin deficiency
Aims of t1m treatment
Reduce mortality
Prevent long term complications (micro and macrovascular issues)
- retinopathy - nephropathy - neuropathy - vascular disease
What is recommended in t1dm for diet (less important than t2dm, but sitll)
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
T/f insulin is only produced after meals
F: there is a basal amount of insulin, makes up 50% of what you need
What does insulin treatment involve
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)
What kind of insulin is used
Genetic engineering to alter absorption,
distribution, metabolism and excretion
Slide 27
Short acting insulin after meals and then background insulin (blue) works for 14 houra
Slide 28
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
When is insulin pump given
Often when pens don’t work (i.e. they keep getting HYPOS)
T/F insulin pump gives only short acting insulu
F… it’s background, then they can inform it when there are food bolus
When are islet cells transplanted
if they keep getting hypos with pens and pumps….
islet cells injected into portal system and produces insulin… must give suppressants
How can the success of treatment be measured
Capillary monitorying/ hba1c
What is capillary monitorig
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
What is hba1c
Relies on RBCs.. glucsose molecules attach to Hb… RBC half life is 120 days, so can measure glucose over 3 month period
When is hba1c not relaible
Haemolysis, or Fe deficiency anaemia
Why is Hba1c useful
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
What is ketosis
rapid decompensation of type 1 diabetes…. involving hyperglycaemia nad metabolic acidosis
Metabolic disturbances in ketoacidosis
hyperglycaemia
- reduced tissue glucose utilisation - increased hepatic glucose production
metabolic acidosis
- circulating acetoacetate & hydroxybutyrate
- osmotic dehydration and poor tissue perfusion
Why do diabetics get hypogylcaemia
occasional hypos inevitable as a result of treating diabetes
major cause of anxiety in patients & families
source of major misconceptions in medi
Define hypoglycaemia vs sever hypoglycaemia
hypoglycaemia - plasma glucose of < 3.6 mmol / l
severe hypoglycaemia - any hypo requiring help of another person to treat
What happebs at glucose:
<3mmol/l
<2mmol/l
most mental processes impaired at <3 mmol/l
consciousness impaired at <2 mmol/l
severe hypoglycaemia may contribute to arrhythmia and sudden death
Long terms effects of hypoglycaemia
may have long-term effects on the brain
recurrent hypos result in loss of warnings= HYPOGLYCAEMIC UNAWARENESS
Who is at risk of hypo
- main risk factor is quality of glycaemic control
- more frequent in patients with low HbA1c (i.e. well controlld)
When does hypo occur
can occur at anytime but often a clear pattern
- pre-lunch hypos common
- nocturnal hypos very common and often not recognised
Why do hypos occur
unaccustomed exercise missed meals inadequate snacks alcohol inappropriate insulin regime
Symptos due to hypoglycaemia
- Due to increased autonomic activation
palpitations (tachycardia) tremor sweating pallor / cold extremities anxiety
- Due to impaired
CNS function
drowsiness confusion altered behaviour focal neurology coma
Hypolycaemia treamtent
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)
Why may glucagon not be given (it can usualyl be but why not)
Glucagon is reliant on there being adequate store of sugar in the liver… if they have been really unwell may not work
Give names of 2 short acting and 2 long acting insulin analogues
short: Lispro, Aspart, Glulisine)
long: (Glargine, Determir, Degludec)
