Cause of Type 1 Diabetes

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Due to selective destruction of pancreatic beta cells by a T-cell-mediated autoimmune process – assumed to occur following an environmental trigger in genetically susceptible individuals  absolute insulin deficiency.

Genetic susceptibility – clusters in families provide evidence for genetic factors – HLA-DR3, –DR4, B8 and B15 predispose to diabetes (account for 40% of the genetic susceptibility). DR2 is protective. However, the majority of those who are genetically predisposed do not develop diabetes. Risk of developing diabetes when close relative has diabetes are 30% for identical twins, 5% for siblings and 6% for offspring.

Environmental - evidence for environmental causes include the wide geographic differences in incidence; the seasonal onset (higher incidence in cooler months); immigrants tend to adopt risk of area they migrate to
– could be viral (several have been implicated – Coxsackie B4, retroviruses, rubella, cytomegalovirus, Epstein-Barr); diet (cow’s milk has been implicated); stress; smoked foods that contain nitrosamines.

Viruses may initiate immune mediated damage to beta cells by direct destruction, by the generation of cytokines that can damage the beta cells or by molecular mimicry  following damage, immune response is initiated.

Dietary factors:
- wheat gluten shown to be diabetogenic in animal modelling of type 1
- common disease specific alleles in celiac disease and type 1 diabetes
- speculated that cow’s milk may trigger type 1 diabetes but this is controversial
- some toxins cause type 1 diabetes in animal models (eg streptozocin)

- Markers of immune mediated damage include:
- islet cell autoantibodies (ICA)
- insulin autoantibodies (IAA)
- glutamic decarboxylase autoantibodies (GAD65)
- tyrosinephosphatases autoantibodies (IA-2, IA-2-beta)
- not all with islet cell antibodies go on to develop diabetes

Individuals are insulin deficient (absolute insulin deficiency) – hyperglycaemia occur when about 75% of beta cells are destroyed.

Non-autoimmune type 1 diabetes:
Immune markers are not found in a small subset of those with ketosis and a variability in their need for insulin. Often are subsequently well controlled with oral agents.
Usually Black or East Asian ethnicity.

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