Neonatal Nutritional Interventions in the Prevention of Type 1 Diabetes

Abstract

After completing this article, readers should be able to: 1. Outline the current concepts of the pathogenesis of type 1 diabetes (T1D) with regard to dietary triggers and genetic susceptibility. 2. Discuss the evidence, both epidemiologic and that derived from studies of animal models, that supports the association between infant feeding practices and T1D. 3. Describe the roles for intestinal immunity and permeability in supporting the hypothetical model of cow milk protein mediation of T1D autoimmunity. 4. Delineate the goals and rationale for prospective clinical trials evaluating neonatal nutrition and the development of T1D. 5. List the putative dietary modulators of T1D. Type 1 diabetes (T1D), a disease that has unacceptably high morbidity and mortality, is increasing in incidence, prompting the redoubling of efforts toward its prevention. Progress toward prevention and cure relies on elucidation of the disease’s pathogenesis, which, to date, has remained poorly defined. The defining features of T1D, insulin deficiency and hyperglycemia, result from an immune-mediated destruction of insulin-secreting beta cells in the pancreatic islets. The loss of beta cell mass is believed to be gradual for most individuals, accounting for the sometimes prolonged asymptomatic periods of autoimmunity preceding overt diabetes (Fig. 1). Indeed, the chronic autoimmune nature of the disease is well established, as is the genetic predisposition. Specific associations with molecules of the human lymphocyte antigen (HLA) define both susceptibility to and protection from T1D. However, T1D is a polygenic disorder with more than 20 loci associated with susceptibility or resistance to the disease, of which the HLA may account for less than 50% of the genetic predisposition. Genetics clearly comprises a major component of the development of T1D, but the interaction between the environment and the immune system abnormalities is believed to weigh heavily in disease development. Indeed, trends in T1D incidence, both geographic and temporal, suggest a strong …