Type 1 Diabetes Mellitus Flashcards
How is T1DM classified (WHO)
Autoimmune destruction of islet cells from an environmental trigger. Leads to insulin deficiency and hyperglycaemia
Describe the pathogenesis of T1DM
- Environmental triggers and regulators along with immune dysregulation leads to destruction of beta cells.
- Eventually auto-antibodies are produced- further destruction
- Patients lose first phase insulin
- All beta cells are destroyed over time.
- Hyperglycaemia
What is the importance of the immune basis of T1DM
Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically
Immune modulation offers the possibility of novel treatments
Describe the epidemiology of T1DM
10% of people with diabetes have T1
Slightly more M than F diagnosed
15x greater risk if first degree relative has diabetes
What are the immune markers for T1DM
Auto-antibodies can be a marker for diagnosis, disease progress, immune modulation treatment:
- Islet cell antibodies (ICA)- grp O human pancreas
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA) – widespread nuerotransmitter
- Insulinoma-associated-2 autoantibodies (IA-2A)-receptor like family
What are the symptoms of diabetes
polyuria nocturia polydipsia blurring of vision ‘thrush’ weight loss fatigue
What are the signs of diabetes
dehydration cachexia hyperventilation smell of ketones glycosuria ketonuria
What are the aims of T1DM treatment
Reduce early mortality
Avoid acute metabolic decompensation
What are some long term complications of T1DM
Retinopathy
Nephropathy
Neuropathy
Vascular disease
What are the diet restrictions recommended for T1DM patients
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
Describe insulin treatment with meals
Short acting
Human insulin
Insulin analogue (Lispro, Aspart, Glulisine)
Describe background insulin treatment
Long acting
Non-c bound to zinc or protamine
Insulin analogue (Glargine, Determir, Degludec)
Describe the insulin pump
Continuous insulin delivery
Preprogrammed basal rates and bolus for meals
Does not measure glucose, no completion of feedback loop
How can diabetes treatment be monitored
Capillary monitoring
HbA1c
What does the reaction of HbA1c red cells with glucose depend on
Lifespan of red cell, about 120 days
Rate of glycation, faster in some individuals
Haemoglobinopathy, renal failure etc
What is the HbA1c test
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 are the acute complications of T1DM
Ketoacidosis
Hyperglycaemia
Metabolic acidosis
What does hyperglycaemia lead to
reduced tissue glucose utilisation
increased hepatic glucose production
What doe metabolic acidosis do
circulating acetoacetate & hydroxybutyrate
osmotic dehydration and poor tissue perfusion
What is the definition of hypoglycaemia
plasma glucose <3.6 mmol/l
severe hypoglycaemia - any hypo requiring help of another person to treat
When can a hypoglycaemic episode occur
Can occur at anytime but often a clear pattern
Pre-lunch hypos common
Nocturnal hypos very common and often not recognised
Which patients are more at risk of hypoglycaemic episodes
Low HbA1c
What may cause a hypoglycaemic episode
unaccustomed exercise missed meals inadequate snacks alcohol inappropriate insulin regime
What are the symptoms of signs of hypoglycaemia due to increased autonomic activity`activation
palpitations (tachycardia) tremor sweating pallor / cold extremities anxiety
What are the symptoms of signs of hypoglycaemia due to impaired CNS function
drowsiness confusion altered behaviour focal neurology coma
What is the oral treatment for hypoglycaemia
glucose
- rapidly absorbed as solution or tablets
complex CHO
- to maintain blood glucose after initial treatment
What is the parenteral treatment for hypoglycaemia
IV dextrose e.g 10% glucose infusion
1mg Glucagon IM
avoid concentrated solutions if possible (e.g 50% glucose)
Describe the genetic aetiology of T1DM
Genetic susceptibility/ protection if you have certain HLA-DR alleles (chrom 6)
Specifically HLA-DR3 and HLA-DR4 increase risk while DR2 is protective
What are the actions of insulin
Reduces:
Hepatic glucose output
Protein breakdown in muscle
Glycerol being taken out of fatty tissue into the periphery
Increases glucose being taken up by the muscle
Describe the mechanism of diabetic ketoacidosis
- Insulin deficiency
- Increased lipolysis
- Fatty acids leave the adipocytes and form ketone bodies instead of glucose
- As fatty acids cannot pass the BBB, ketones are produced for the brain
- Ketones cause an acidic environment
- Osmotic dehydration due to brain enzyme dysfunction
- Poor tissue diffusion
What is LADA
Latent autoimmune diabetes in adults - presentation of autoimmune type 1 diabetes that leads to insulin deficiency
What is the relapsing and remitting disease theory
levels of effector T cells (that cause destruction of beta cells) and regulatory T cells (that control this destruction) fluctuate but over time effector T cells increase in number
