The concept is that low doses of orally administered autoantigens suppress autoimmunity by inducing antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines at the target organ ( 5– 7). Peptides derived from an orally administered antigen encounter the mucosal gut–associated lymphoid tissue, which serves both to protect the host from ingested pathogens and to prevent the host from reacting to ingested proteins. A number of studies have suggested that oral administration of autoantigens induces protective immunity that has the potential to downregulate ongoing destructive immune reactions ( 5– 7). Type 1 diabetes is a consequence of immune-mediated destruction of insulin-secreting pancreatic islet β-cells ( 4). Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels. However, oral insulin did not delay or prevent type 1 diabetes. In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) ≥80 nU/ml ( n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015).ĬONCLUSIONS-It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). RESULTS-Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects.
The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. Oral glucose tolerance tests were performed every 6 months. A total of 3,483 were antibody positive 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes 388 had a 5-year risk projection of 26–50% and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. RESEARCH DESIGN AND METHODS-We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. OBJECTIVE-This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes.
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