Clinical onset generally acute, but T-cell mediated selective destruction of beta cells would have been progressive for many years prior to diagnosis – preclinical stage may be up to 5 – 7 years. The circulating islet cell antibodies can be detected in this preclinical stage even though they are still normoglycaemic (remaining beta-cells can produce enough insulin)
Hypothetical stages:
1. Genetic susceptibility
2. Triggering of immune response by environmental agent
3. Autoimmunity develops – antibodies detectable include ICA (islet cell antibodies), IAA (insulin autoantibodies) and anti-GAD.
4. Pre-diabetes (loose first phase insulin response)
5. Clinical diabetes
6. Remission (honeymoon phase)
7. Relapse – need insulin for survival
Pathological features of the pre-diagnosis pancreas are typically:
insulitis
infiltration of the islets by mononuclear cells – macrophages, T lymphocytes, natural killer cells and B lymphocytes indicative of inflammation (insulitis)
patchiness of lesion – areas are unaffected
beta cells are specifically attacked (other hormone secreting cells unaffected)
As insulin is deficient increase in gluconeogenesis, lipolysis and ketogenesis ketoacidosis (do not get ketoacidosis in type 2)
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