pathogenesis of type I diabbetes (IDDM)
Last edited 03/2018 and last reviewed 04/2021
The pathogenesis of IDDM is one of slow, progressive immunological destruction of the beta cell mass by antigen specific cytotoxic T-lymphocytes augmented by cytokine release from macrophages and NK-Cells.
The loss of beta cells is slow and one can detect progressive glucose intolerance over time. Symptomatic diabetes mellitus and insulin dependence occurs only when the beta cell mass is reduced to 10% of normal and often presents acutely as a result of an increase in insulin resistance associated with puberty or concurrent infection.
Although the humoral immune response is not thought to play an important role in the destruction of beta cells a number of autoantibodies have been identified and are of some predictive significance:
- cytoplasmic islet cell antibodies (ICA) are present in approximately 80% of newly diagnosed IDDM patients
- family members of IDDM patients who have islet cell antibodies are at an increased risk of developing diabetes themselves and furthermore the magnitude of this risk is related to the titres and persistence of their ICA response
- glutamic acid decarboxylase (GAD) autoantibodies have also been identified and shown to be present before IDDM is diagnosed
- anti-insulin antibodies have also been studied
- the presence of ICA and anti-insulin antibodies is highly predictive for IDDM