Advances and controversies in etiopathogenesis of type 1 (insulin- dependent) diabetes mellitus

Emanuele Bosi, Elena Sarugeri

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The present state of knowledge and controversies about the etiopathogenesis of type 1 diabetes can be summarized as follows: Genetics: MHC class II genes (IDDM1) confer the strongest susceptibility with a hierarchy 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. Environment: 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. Autoimmunity: 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.

Original languageEnglish
Pages (from-to)293-305
Number of pages13
JournalJournal of Pediatric Endocrinology and Metabolism
Issue numberSUPPL. 2
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Endocrinology
  • Pediatrics, Perinatology, and Child Health


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