Type 1 Diabetes is an autoimmune disease characterised by pancreatic β cell destruction and an absolute deficiency of insulin
Accounts for approximately 5% and 10% of all cases
Most common type diagnosed in patients younger than 20 years
Pathogenesis
The fundamental immune abnormality is failure of self tolerance in T cells
This is due to combination of defective clonal deletion of self reactive T cells in the thymus as well as defective regulatory T cells or resistance of effector T cells to suppression by regulatory cells
Develops in childhood, manifests in puberty and progresses with age
Inaccurate to call as “juvenile diabetes” as it can occur at any age
GENETIC SUSCEPTIBILITY
Genetic susceptibility loci for type 1 diabetes is HLA gene cluster on chromosome 6p21
Individuals who have either DR3 or DR4 concurrently with DQ8 haplotype – highest risk
Insulin gene – variable number of tandem repeats in the promoter region are associated with disease susceptibility. The polymorphism affects the level of expression of insulin in the thymus, thus affecting the negative selection of insulin reactive T cells
Other genes involved are
– CTLA4 and PTPN 22 (autoimmune thyroiditis)
– AIRE (Autoimmune polyendocrinopathies)
ENVIRONMENTAL FACTORS
Viral infection – ´Virus might share epitopes with islet antigens and immune response to virus results in cross reactivity and destruction of islet tissue (molecular mimicry)
The initial activation of immune cells occur in peripancreatic lymphnodes probably in response to antigens that are released from damaged islets
Islet autoantigens that are targets of immune attack may include
– Insulin
– β cell enzyme glutamic acid decarboxylase
– Islet cell autoantigen 512 (ICA512)
´But the roles of antibodies in type 1 Diabetes is suspicious
Reference-
Anirban Maitra. The Endocrine system.In: Robbins and Cotran Pathologic basis of disease.9th edition.volume II.chapter 24. pp 1073-1141.
