The concept that idiopathic diabetes mellitus is a genetically heterogeneous group of disorders has been established by twin and HLA studies that have permitted the separation of juvenile-onset and maturity-onset diabetes. The extent of the heterogeneity within the juvenile-onset and maturity-onset types is still in question. On the basis of recent inununologic and metabolic studies we believe that further heterogeneity can be demonstrated within the juvenile-onset diabetic group. We wish to hypothesize that there are at least two distinct forms of juvenile-onset diabetes, one associated with HLA B8 and the other with BW15. The B8 type is characterized by autoimmunity, microangiopathy, and a stronger association with the HLA D locus. The BW15 type is characterized by antibody response to exogenous insulin and a stronger association with the HLA C locus. Greater understanding of the pathogenesis, natural history, and genetics of diabetes mellitus will result as the full extent of genetic heterogeneity is elucidated.

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