Update on worldwide efforts to prevent type 1 diabetes

Abstract

This paper reviews worldwide efforts to interdict the type 1 diabetes (T1D) disease process, during the stage of evolution of the disease prior to the time of disease onset. The goal of intervention before disease onset is to arrest immune destruction and thus prevent or delay clinical disease. In this regard, there have been several large-scale multicenter randomized controlled clinical trials designed to prevent T1D. These have tested nicotinamide, parenteral insulin, oral insulin, nasal insulin, and the elimination of cow's milk from infant feeding.

Figure 1

Schematic depiction of potential timing of interventions to interdict the type 1 diabetes disease process. This can be in genetically at-risk newborns or young children prior to detection of autoimmunity, in individuals with diabetes autoantibodies, in those with autoantibodies plus a metabolic defect -either loss of first phase insulin response to intravenous glucose or the presence of dysglycemia on an oral glucose tolerance test; or at the time of diagnosis of type 1 diabetes (or shortly thereafter).

Figure 2

Cumulative incidence of type 1 diabetes in the nicotinamide and placebo arms of the ENDIT study. Adapted from Lancet 2003; 363: 925–931.

Figure 3

Life-table depicting time to diagnosis of type 1 diabetes in the DPT-1 parenteral insulin trial. Adapted from New Engl J Med 2002; 346:1685–91.

Figure 4

Life-table depicting time to diagnosis of type 1 diabetes in the DPT-1 oral insulin trial. Adapted from Diabetes Care 2005; 28:1068–76.

Figure 5

Life-table depicting time to diagnosis of type 1 diabetes in the DPT-1 oral insulin trial, for the subset of subjects with baseline confirmed insulin autoantibody level of 80 nU/ml or above. Adapted from Diabetes Care 2005; 28:1068–76.

Figure 6

Life-table depicting time to diagnosis of type 1 diabetes in the DPT-1 oral insulin trial, for the subset of subjects with baseline confirmed insulin autoantibody level of 300 nU/ml or above. From an analysis by Todd MacKenzie PhD, Dartmouth University, conducted for NIDDK.