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

Abstract

The present state of knowledge and controversies about the etiopathogenesis of tyep 1 diabetes can be summarized as follows:

GENETICS:

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.

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.

• Authors: E Bosi, E Sarugeri
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 11 Suppl 2 Pg. 293-305 (Apr 1998) ISSN: 0334-018X [Print] Germany
• PMID: 9642660 (Publication Type: Journal Article, Review)

Topics

• Animals
• Autoimmune Diseases (epidemiology, etiology, genetics)
• Cattle
• Diabetes Mellitus, Type 1 (epidemiology, etiology, genetics)
• Disease Susceptibility
• Environmental Illness (epidemiology, etiology)
• Genes, MHC Class II
• Humans
• Incidence
• Milk (adverse effects)
• Risk Factors
• Virus Diseases (complications, epidemiology)