T1DM Flashcards
T1DM Classification?
COMPLETE LACK of insulin
T2DM Classification?
RELATIVE LACK of insulin & INSENSITIVITY
How is the Classification of Diabetes ambiguous?
o Autoimmune T1DM can present later in life
- as LADA (latent autoimmune diabetes in adults)
o T2DM can present in childhood (however more common in adult life)
o DIABETIC KETOACIDOSIS (DKA) is only a feature of T1DM
- In T2DM, insulin production is sufficient to supress ketone production (although can present)
o Monogenic diabetes can present as T1 or T2 (e.g. MODY)
o Diabetes may present
Classification of diabetes based on aetiology?
Genetics can play a role in BOTH
BUT
o T2 is more hereditary (genetic play a larger role)
o T1 is usually autoimmune
The beta-failure in T2 is RELATIVE
- the cells still make lots of insulin, it just is NOT enough to stimulate the insulin receptors
What is the pathogensis of T1DM?
There are multiple relapse-remitting processes
o including Abs destroying beta-islet cells
Honeymoon Phase?
Last instance where the beta-cells produce a NON-hyperglycaemic response with just enough insulin
Role of T-cells in T1DM?
Effecter T-cells are destructive
AND
the T-reg cells are supposed to keep them in check
EVENTUALLY the T-effector cells overcome the T-reg cells = DESTRUCTION OCCURS
How does patient w. T1DM have an immune background?
o Increase prevalence of other autoimmune disease
o Risk of autoimmunity in relatives
o More destruction of B-cells
o Auto-Abs to confirm T1DM
o Immune modulation offers possibility of novel treatments
HLA-DR allele?
HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on Chr6
Genetic susceptibility in regards to HLA-DR?
HLA-DR3/4 deletion
o provides significant risk
Envrionmental triggers for T1DM?
More T1DM patients present in winter/autumn months
POSSIBLE INFECTIOUS CAUSE
Markers for T1DM?
Normally do NOT need to measure
o Islet cell Abs o Insulin Abs o Glutamic acid decarboxylase (GADA) -NTs o Insulinoma-associated-2 autoAbs (IA-2A) - Receptor
C-peptide and first phase insulin?
C-peptide marker of insulin production
o If C-peptide REDUCES = Insulin deficient
Auto-Abs make patient lose their first phase insulin
o indicator of diabetes in later life
Symptom presentation of T1DM?
o Polyuria o Nocturia o Polydipsia o Blurring of vision o 'Thrush' o Weight loss o Fatigue
Sign presentation of T1DM?
o Dehydration o Cachexia - muscle wasting/weakeness o Hyperventilation - have metabolic acidosis so Kussmahl breathing o Ketone smell o Glycosuria o Ketonuria
Liver, muscles and adipoytes?
o Liver is a large source of glucose
- mainly from GLYCEROL
o Aa from muscle goes OUT into circulation
- can be taken up by the liver
o Adipocytes have TGs
- can be broken down into glycerol + FAs
Negative effects of insulin on body?
o HGO
o Protein breakdown in the muscle
o GLYCEROL being taken out from fatty tissue into the periphery
Positive effect of insulin on body?
o Glucose being taken UP by muscle
What does insulin deficiency mean then?
A lot of glucose goes OUT into circulation
BUT
is NOT taken up by tissues
ALSO enables GLYCEROL to leave cells
o and TGs breakdown
o SO are THIN!!
Mechanism of DKA?
Diabetic Ketoacidosis
Normally:
o glycerol leaves adipocytes + enters liver
BUT in insulin deficiency:
o FAs come out of adipocytes + enter liver
o converted to KETONES (normally inhibited by insulin)
Link between insulin deficiency & ketone bodies?
Deficient in insulin = MORE ketone bodies produced by liver
Casues ketonuria
What are the aims of T1DM treatment?
o Reduce early mortality
o Avoid acute metabolic decomposition
o Prevent long-term complications
- e.g. retino/neuro/nephropathy, vascular disease
What type of treatment to T1DM patients require?
EXOGENOUS Insulin!
Ketones define the insulin deficiency
What are the diet changes required in those w. T1DM?
o Reduce calories as fat
o Reduce calories as refined carbs
o Increase calories as complex carbs
o Increase soluble fibre
Distribute food evenly throughout the day with regular meals and snacks
