Pathophysiology of Type 1 Diabetes Flashcards Preview

DEMS: Unit II > Pathophysiology of Type 1 Diabetes > Flashcards

Flashcards in Pathophysiology of Type 1 Diabetes Deck (11)
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Progression from normal ==> overt T1D

  • T1DM is a slowly progressive largely T-Cell mediated autoimmune illness. Antibodies play a minor role.
  • Genetic susceptibility
  • Some precipitating event is that starts autoimmune process and β cell destruction, silent
  • Labile blood sugars eventually
  • This time course can take years, variable from person to person


Positive antibody (possible) in T1D

  • Diabetes Associated Autoantibodies (DAA)
    • against proteins in the the islet can be found years prior to diabetes diagnosis.
  • Islet Cell Antibodies (ICA or IA-2, GAD65)
  • Insulin Autoantibody (IAA)
  • Zinc Transporter Ab (ZnT8) 
  • Multiple antibodies has a much higher risk of getting T1D than single antibody


Environmental factors associated w/T1D

  • Occurs in lean kids
  • Incident Event-unsure of what environmental factors these may be but cause “Silent” β-cell loss.
  • Infections: e.g. Virus
  • Diet
  • Hygiene hypothesis
  • Accelerator hypothesis


Possible role of diet in development of T1D

  • Increased incidence with shorter duration of breastfeeding AND
  • earlier introduction of cow’s milk and cereals


"Hygiene hypothesis" & T1D

  • we are too clean!
  • Immune system is bored and attacks normal β cells instead


Accelorator hypothesis & T1D

  • Accelerator hypothesis → link between childhood obesity and increase in the incidence in T1D.
  • Obesity leads to β-cell stress exposing β-cell antigen to the immune system and initiating an immune response.


Genetic factors that predispose to T1D

  • HLA is the strongest genetic predictor. 
    • Class 2 HLA is most important: DQ, DR;
    • DR 3/4 - DQ8 and DR 4/4-DQ8 are the highest risk
  • The insulin gene IDDM2 is the 2nd highest genetic risk factor
    • VNTR Class I (few copies of promoter = less insulin expression in thymus) is higher risk
  • Risk of HLA DR3/4 + VNTR Class I is additive



Familial/ethnic genetic factors that predispose to T1D

  • Most common in younger, white children
  • Risk for developing multiple Ab is much higher if both parents or a parent + sibling have diabetes


Protective genetic factors against T1D

  • IDDM2 (insulin gene) locus:
    • VNTR Class III is protective


Immune system components involved in T1D

  • T cell mediated damage against β cells as a result of Diabetes Associated Antibodies (DAA).
  • Both CD4 and CD8 T-cells play a role.
  • The autoimmune attack against the β-cells can be identified by the presence of autoantibodies against islet proteins in the sera of at risk individuals and are predictive of development of the disorder