Type 1 diabetes
- Mechanism
In type 1 diabetes, the immune system destroys the insulin-making cells. People need insulin for life.
What it is
Type 1 diabetes is an autoimmune disease in which T cells destroy pancreatic beta cells. Autoantibodies appear years before symptoms, and the disease becomes overt when most beta cells are gone. It usually starts in childhood or adolescence, though it can begin at any age, and it shares HLA risk with other autoimmune diseases.
Structure
- Early: lymphocytic infiltrate (insulitis), mainly CD8 T cells, in and around islets.
- Late: small islets made only of non-beta cells; insulin immunostaining is absent.
- Exocrine pancreas: atrophy and a smaller organ.
- Insulin-dependent childhood diabetes can also be seen in infants of diabetic mothers as beta-cell hyperplasia (a different, reactive change).
Step by step
- A genetically susceptible child (HLA-DR3/DR4-DQ8) has defective central and peripheral tolerance to beta-cell antigens.
- An environmental trigger (perhaps a virus) injures beta cells and exposes antigens.
- Autoreactive CD4 T cells are activated and help CD8 T cells and B cells; autoantibodies appear.
- CD8 T cells and cytokines destroy beta cells progressively over years (insulitis).
- When roughly most of the beta-cell mass is lost, hyperglycaemia appears; a brief honeymoon may follow insulin start.
Markers
- GAD65 antibody
- IA-2 antibody
- Insulin autoantibody
- ZnT8 antibody
- Low C-peptide
Clinical notes
- Onset is often with diabetic ketoacidosis.
- Latent autoimmune diabetes of adults (LADA) is slow-onset type 1 that can be mistaken for type 2.
- Associated autoimmunity: Hashimoto thyroiditis, coeliac disease, Addison disease (APS-2).
Test yourself
Think of the answer, then tap the question to see it.
Which HLA haplotypes carry the highest risk for type 1 diabetes?
HLA-DR3 and DR4, especially with DQ8 (DR3/DR4 heterozygotes have the highest risk).
What is insulitis?
A lymphocytic, mainly CD8 T-cell, infiltrate in and around the islets during active beta-cell destruction.
Which three islet autoantibodies are used in type 1 diabetes?
Anti-GAD65, anti-IA-2, anti-insulin (also anti-ZnT8).
Elsewhere in DurgiPedia
- HLA associations with disease
- Immune tolerance and how autoimmunity begins
- Molecular mimicry and post-infectious autoimmunity
- CD8⁺ cytotoxic T cell
- Autoantibodies: the table to know
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Diabetes Type 1 (MedlinePlus, US National Library of Medicine, 2025); Type 1 diabetes (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.