Type 1 Diabetes Flashcards
What is type 1 diabetes?
An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
The resultant hyperglycaemia requires life-long insulin treatment
What causes type 1 vs type 2 diabetes
Type1 : Environmental trigger and genetic risk
Leads to autoimmune destruction of islets
Absolute insulin deficiency
Type 2: Genetic risk and Obesity
Insulin resistance
Relative insulin deficiency
Why do we measure c peptide instead of insulin
As c peptide has a longer half life
And insulin can be given so when measured won’t know if it due to what has been given or it is being produced
What are the stages of development of type 1 diabetes?
Genetic predisposition
Potential precipitating event
Overt immunological abnormalities; normal insulin release
Progressive loss of insulin release; glucose normal
Overt diabetes; c-peptide present
No C-peptide present
Genetic risk
Immune activation
Immune response - development of single autoantibody
Why is the immune basis important
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
Not there yet
Explain a brief overview of immunology in type 1 diabetes
Defect in innate and adaptive immune system
Primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
Exacerbated by release of pro-inflammatory cytokines
Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity
Why is it a positive that some Beta cells are not destroyed in type 1 diabetes
Shows that some are avoiding the immune system
When you have a low blood sugar and too much insulin is given and heading towards a hypo, pancreas can switch of insulin production
Less likely to develop microvascular complications later on
What allele does the biggest genetic susceptibility come from?
HLA -DR allele
(Human leukocyte antigen)
DR3 +4
What are environmental factors for type 1 diabetes
Dip during Summer
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What are pancreatic auto-antibodies detectable in the sera of people with type 1 diabetes at diagnosis
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
What are the presenting symptoms of type 1 diabetes
Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
What are the presenting signs of type 1 diabetes
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
What is the diagnosis of type 1 diabetes based on
DIAGNOSIS IS BASED ON CLINICAL FEATURES and presence of ketones (in some cases pancreatic autoantibodies / C-peptide may be measured)
What happens with an insulin deficiency
Protienolysis into amino acids
Hepatic glucose output increases (counter-intuitive)
Lipolysis increases so more glycerol and NEFA
What happens when NEFA is taken up by the liver
More Beta oxidation and ketone bodies made
Can cause ketoacidosis
What are the aims of treatment in type 1 diabetes
Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications
