Advances and controversies in etiopathogenesis of type 1 (insulin-dependent) diabetes mellitus.
The present state of knowledge and controversies about the etiopathogenesis of tyep 1 diabetes can be summarized as follows:


BACKGROUND
MHC class II genes (IDDM1) confer the strongest susceptibility with a hierachy DQ > DR; more than ten other chromosome regions (IDDM2 to IDDM13) have been identified as candidates for linkage with type 1 diabetes: currently, there is consensus for insulin (IDDM2) and a few other loci, while the remainder await confirmation.


METHODS
The role of milk as a trigger is debated. In fact, the protective effect of breast feeding is marginal, while the immune response to milk proteins in type 1 diabetics is very heterogeneous; moreover, the putative autoantigens showing sequence homology with milk proteins have been questioned. With regard to viruses, seasonal variations of incidence have been confirmed, although not uniform across countries; serological studies are controversial, while isolation of viruses from diabetic pancreases remains anecdotal; very interesting is the demonstration of enteroviral infection in pregnant mothers of future diabetic children, although this does not prove a causal role; a new frontier of investigation could be that of endogenous retroviruses acting either as autoimmune genes or infectious agents.
GAD65, IA2 and insulin are at present the only established autoantigens; autoantibodies to these molecules, used in combination with ICA, can accurately predict type 1 diabetes; B-lymphocytes and autoantibodies might play a pathogenetic role; autoantigen targets of T-lymphocytes are yet to be characterized; assays for measuring autoreactive T-lymphocytes require standardization; antigen-specific Th1/Th2 relationship in type 1 diabetes remains controversial.
Bosi
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Istituto Scientifico Ospedale San Raffaele, Università di Milano, Milan, Italy.
Sarugeri
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D000818:Animals; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D002417:Cattle; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D004198:Disease Susceptibility; D018876:Environmental Illness / Q000453:epidemiology / Q000209:etiology*; D005802:Genes, MHC Class II; D006801:Humans; D015994:Incidence; D008892:Milk / Q000009:adverse effects*; D012307:Risk Factors; D014777:Virus Diseases / Q000150:complications* / Q000453:epidemiology