Risk Factors for Type 1 Diabetes

Excerpt

Type 1 diabetes can be diagnosed at any age, but the incidence rate is highest in adolescence, and most available data on risk factors are on children and adolescents. The disease is likely caused by a combination of genetic and environmental factors. This article focuses primarily on environmental risk factors, while the genetics of type 1 diabetes is extensively covered in a separate Diabetes in America article and addressed only briefly herein. The incidence of type 1 diabetes is increasing at an average annual rate of 2%–5%, which suggests a major environmental exposure has changed, by either the gradual introduction of a susceptibility factor or the removal of a protective factor, during the past 60 or more years. Outbreaks and seasonality of type 1 diabetes may suggest an infectious cause, perhaps related to improving sanitation and loss of herd immunity. Early childhood diet and environmental toxins are also of interest.

Prospective studies following high-risk children from birth to development of the subclinical phase of the disease (islet autoimmunity) and diabetes have been the most reliable source of information regarding risk factors for type 1 diabetes. Prenatal and early postnatal exposures appear to be critical, as the incidence of islet autoimmunity peaks in the second year of life. Among infectious agents, enteroviral infections, particularly if they are acquired in infancy and persistent, have gained the most interest. Early leads suggesting a role for cow’s milk exposure in the initiation of islet autoimmunity have not been confirmed by large prospective studies and a large, randomized clinical trial. While numerous prospective studies have reported 1.5–2-fold increases in the risk of islet autoimmunity or type 1 diabetes with various components of early childhood diet and infectious exposures, none of the associations appears particularly strong or consistent across different populations.

Type 1 diabetes is likely caused by the interplay of genetic and environmental factors. Systematic investigation of gene-environment interactions in large, prospectively followed cohorts of young children may help the field identify and fully characterize modifiable risk factors and design trials to evaluate the strongest candidate triggers of autoimmunity.