PATHOGENESIS OF TYPE

1 DIABETES MELLITUS
NURUL SYAFIQA BINTI SADHIK BATCHA
182455

TYPE 1 DM
Type 1 diabetes results from insulin deficiency caused by the loss of insulin-producing
pancreatic b cells
Generally develops in the young
The development of type 1 diabetes is the consequence of progressive b cell destruction by
autoimmune processes during an asymptomatic period that often extends over many years.
Genetic susceptibility is believed to be a prerequisite
However their concordance rate is only 40%
Suggesting that environmental or nongenetic factors contribute to the development of the
disease.
Histologic analysis of the pancreas from patients with recent-onset type 1 diabetes revealed an
infiltration of the islets of Langerhans by mononuclear cells which were later
identified as T and B lymphocytes, monocytes/macrophages, and natural killer (NK)
cells, circulating islet-reactive autoantibodies and islet-reactive T cells have been
found in patients with type 1 diabetes

AUTOIMMUNE

IMMUNE SYSTEM ATTACK SELF ANTIGEN

PATHOGENESIS
Pancreatic b cell autoantigens are the targets of immunemediated destruction of b
cells.
One of the most common immunologic markers of humans and animals with
autoimmune diabetes is the presence of autoantibodies and autoreactive T cells
directed against b cell autoantigens.
These autoantigens include insulin, glutamic acid decarboxylase (GAD)65, tyrosine
phosphatase, insulinoma antigen (IA)-2 and IA-2b, carboxypeptidase-H, islet cell
antigen (ICA)-69 GM gangliosides a 38-kd autoantigen, and SOX13.
Autoantibodies against these b cell autoantigens are not believed to have a
pathogenic role
The risk of developing diabetes is strongly related to the number of autoantibody
markers, that is, the presence of 2 or more autoantibodies gives a higher probability
of developing the disease than the presence of a single autoantibody

DM TYPE 1
Environmental factors in human type 1 diabetes.
There is evidence in experimental models that infections can trigger
autoimmune reactions to -cells. Molecular mimicry between viral
proteins and -cell transgenes
GENETIC FACTOR HIGHLY MULTIGENIC
Associated with HLA

REFERENCES
http://
www.columbia.edu/itc/hs/medical/pathophys/immunology/readings/IsetCel
lDestructionReview.pdf
Lernmark A, Falorni A. Immune phenomena and events in the islets in
insulin-dependent diabetes mellitus. In: Pickup JC, Williams G, eds.
Textbook of Diabetes, 2nd ed. Oxford: Blackwell Science; 15.115.23.
Atkinson MA, McLaren NK. The pathogenesis of insulin-dependent
diabetes mellitus. N Engl J Med. 14281436.
http://diabetes.diabetesjournals.org/content/54/suppl_2/S87
http://perspectivesinmedicine.cshlp.org/content/2/11/a007641.full