Environmental triggers of type 1 diabetes

Abstract

Type 1 diabetes (T1D) is perceived as a progressive immune-mediated disease, the clinical diagnosis of which is preceded by an asymptomatic preclinical period of highly variable duration. It has long been postulated that the disease process leading to overt T1D is triggered by an infectious agent, the strongest candidate being a diabetogenic enterovirus. The initiation and progression of the disorder likely requires, in addition to genetic T1D susceptibility, a trigger, an exogenous antigen capable of driving the development of this disease. This may be a dietary antigen similar to gluten in celiac disease. Recent data further suggests that the initiation of autoimmunity is preceded by inflammation reflected by a proinflammatory metabolic serum profile. The cause of the inflammation remains open, but given that the intestinal microbiome appears to differ between individuals who progress to clinical T1D and nonprogressors, one may speculate that changes in the gut microflora might contribute to the inflammatory process.

Figure 1.

Progression from genetic disease susceptibility to overt T1D. The appearance of signs of β-cell autoimmunity is preceded by a proinflammatory state, the etiology of which is so far open.

Figure 2.

The odds ratio for an association between a Coxsackie virus B1 infection and seroconversion to two or more diabetes-predictive autoantibodies increases over time and is highest in the first sample with detectable β-cell autoimmunity.