The Heterogeneity of Diabetes Unraveling a Dispute: Is Systemic Inflammation Related to

Diabetes is an emblematic example of a heterogeneousdisease. Systemic inflammation has emerged as a promi-nent factor in the type 2 diabetes pathoetiology, but itremains ill-defined in type 1 diabetes. There is a widespectrum of associations between inflammatory responsesand diabetic syndromes. At one end of this spectrum, thereis type 1 diabetes for which there is convincing evidencethat chronic inflammation of pancreatic islets is a centralaspect of disease pathogenesis. At the opposite end, is type2 diabetes that is clearly associated with systemic inflam-mation, which could be either the cause or simply mark theunderlying pathology. Accumulating evidence has substan-tiated that a subgroup of adult patients clinically diag-nosed with type 2 diabetes exhibit autoantibody responsesto islet autoantigens. The presence of these immunologicabnormalities is associated with a severe insulin secretorydefect and the absence of signs of systemic inflammation asdocumented by plasma C-reactive protein and fibrinogenlevels that are comparable with those of control popula-tions. Islet autoantibody evaluation should be part of thediagnostic assessment for clinically diagnosed type 2 dia-betes not only because it might predict the rate of progres-sion to insulin requirement in adult populations but also toidentify a pathogenically distinct disease phenotype char-acterized by the absence of systemic inflammation and itsrelated disorders. A more appropriate characterization ofthis subgroup of clinically diagnosed type 2 diabetes, dia-betes of autoimmune pathogenesis, will promote futureresearch into the etiology, natural history, and treatment.