Pathogenesis of type 1 diabetes: implications for incidence trends.

BACKGROUND

The incidence of type 1 diabetes (T1D) has increased markedly after World War II among children and adolescents, while the mean age at diagnosis has decreased. These trends support a critical role of exogenous factors in the development of T1D, since genetic factors alone can hardly explain the rapid increase. Evidence supporting a crucial role of environmental determinants in the pathogenesis of T1D includes: (a) the fact that <10% of those with human leukocyte antigen-conferred diabetes susceptibility progress to clinical disease; (b) a pair-wise concordance of T1D of <40% among monozygotic twins; (c) a close to 20-fold difference in the disease incidence among Caucasians living in Europe, and (d) migration studies indicating that the incidence increases in population groups who have moved from a low- to a high-incidence region.

CONCLUSIONS

Accumulating data suggest that the T1D disease process may be triggered by a diabetogenic enterovirus infection and driven by a dietary antigen. The strongest candidate for the latter is bovine insulin, which differs from human insulin by three amino acids. The increasing disease incidence and decreasing age at diagnosis will culminate in an increased number of patients with a longer disease duration and, eventually, an increased frequency of macro- and microvascular complications if the trend cannot be counteracted by improved metabolic control.