1b T1DM Flashcards
What is T1DM?
an autoimmune condition in which insulin producing beta-cells in the pancreas are
attacked and destroyed by the immune system
What does the resultant hyperglycaemia result in?
the need for life long insulin treatment
What are the triggers of type 1 diabetes which can lead to an autoimmune destruction of islets?
Environmental triggers
Genetic risk
How does T1DM lead to hyperglycaemia?
Absolute insulin deficiency
What is MODY?
Maturity Onset Diabetes of the Young
What is C-peptide?
A cleavage product of pro-insulin
What is pro insulin cleaved into?
Insulin and C peptide
What happens in the stages A and B of the diabetes onset graph?
Normal B cell Mass results in normal insulin production
What happens at stage C in the diabetes onset graph?
Genetic predisposition
What happens after the C stage in the diabetes onset graph?
Progressive loss of insulin release, glucose levels normal and then eventually Overt diabetes
What happens in the G stage of diabetes in the graph?
Overt diabetes, C peptide Present
What happens in the H stage of diabetes in the graph?
No C peptide and no insulin present
What are the pancreatic Beta cells attacked with?
Pancreatic autoantibodies = immune activation
Why is the immune basis of T1DM important?
- Increased risk of other autoimmune conditions
- Risk of autoimmunity on relatives
- More destruction of Beta Cells
Are all the beta cells destroyed in T1DM?
No = some people with type 1 diabetes continue to produce insulin but not enough to negate the need for insulin therapy
Which HLA-DR genes pose a significant risk to the genetic susceptibility of Diabetes?
DR3 and DR4
What are four environmental factors which might contribute to the implications of T1DM?
- Enteroviral infections
- Cow’s milk protein exposure
- Seasonal variation
- Changes in microbiota
Where are pancreatic autoantibodies detectable?
Detectable in the sera of people with Type 1 diabetes at
diagnosis.
What are three examples of pancreatic autoantibodies which are detectable?
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA) – widespread
neurotransmitter - Insulinoma-associated-2 autoantibodies (IA-2A)-Zinctransporter 8 (ZnT8)
What are the symptoms of T1DM?
Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
What are the signs of T1DM?
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
What is the diagnosis of T1DM based on?
CLINICAL FEATURES and presence of ketones
What are the effects of insulin deficiency on the muscle?
Proteinolysis resulting in more Amino acid
What are the effects of lack of insulin on the liver?
Hepatic glucose output increases resulting in more glucose
what are the effects of lack of insulin on the fat cells?
Lipolysis increases resulting in more NEFA
Describe how ketone bodies are produced?
NEFA taken into the liver
Beta Oxidation - Fatty Acyl CoA is converted into Acetyl CoA which is then made into Acetoacetate, Acetone and 3 Hydroxybutyrate (ketone bodies)
What are ketone bodies?
Fuel source in times of starvation
Why can ketone bodies become problematic?
they are acidic, therefore too many results in the blood becoming more acidic and an accumulation of H+
what is the effect of insulin on beta oxidation?
insulin inhibits it, stimulated by glucagon
What is the treatment for someone with T1DM?
Insulin for life