Now Is the Time to Prevent Type 1 Diabetes

T DISCUSSANTS of this question represent opposing positions that are reflected in their obligatory Y2K compliance statements. Schatz et al. (1) state that, “As we move into the new millennium, there is hope that these and future studies will make prevention of the disease a reality in the not too distant future. ” Becker et al. (2) aver, “The risks of the intervention should be weighed clearly against the risks and discomfort of the treatment of diabetes as we approach the next millennium. ” Schatz et al. (1) are key players in the United States diabetes prevention trial, DPT-1, whereas Becker et al. (2) in Pittsburgh are perhaps the only large group of academic pediatric diabetologists not participating in a secondary prevention trial. The prominence of the latter group in studies of the etiology and natural history of diabetes makes it important to consider the reasons for this position. The Pittsburgh brief begins with the assertion that any disease prevention has three major prerequisites: identification of those at risk, identification of the etiology or precipitating factor, and some understanding of pathogenesis. The fundamental prerequisites of the DPT-1 group, on the other hand, are that the disease be a demonstrated burden, that high-risk individuals be accurately identified, and that treatment is available that is safe, rational, and with the potential to be effective. These sets of prerequisites only agree on the point of identification of those at risk. The prerequisites put forth by Schatz et al. (1) are those usually associated with justification for screening a population; they are also more broadly applicable to our experience with successful disease prevention efforts. For example, smallpox was effectively prevented in a number of populations long before development of the germ theory (i.e. the understanding of etiology and pathogenesis of the disease; Ref. 3). It is conceivable that a preventive such as avoidance of bovine milk protein might work and be broadly applied before there is a coherent explanation for its role in the pathogenesis of diabetes. Schatz et al. (1) outline the burden of diabetes, the inadequacy of treatment, and the profound importance of prevention, consistent with their first prerequisite, and this importance is inarguable. They consider that reducing prevalence rates by as little as 10–15% would be sufficient justification for intervention, in view of the gravity of diabetes. Becker et al. (2) would seem to not agree with this, because of their concern that immune markers, at best, connote a 50% risk of developing diabetes over the subsequent 5 yr, and that 10% of relatives identified as low-risk also develop diabetes. This is an issue of statistical power and informed consent. Despite these limitations, substantial numbers of families have chosen to be a part of these pilot studies. A recent report from Finland suggests considerably better predictability with available immune and metabolic markers than suggested in the review by Becker et al. (2). Siblings of children with recent onset type 1 diabetes mellitus were classified into four stages depending on whether there were no antibodies (“no prediabetes”), one antibody specificity (“early prediabetes”), two antibodies (“advanced prediabetes”), and more than three antibodies (“late prediabetes”). Six hundred sixty-one siblings were classified thusly and followed, and another 712 siblings were classified using first phase insulin response (FPIR) to iv glucose; that classification was no (no antibodies), early (one antibody specificity, normal FPIR), and late prediabetes (one or more antibodies, reduced FPIR). Followup was an average of 9 yr, during which only 0.9% in both groups who were classified as no prediabetes went on to develop the disease. The progressive classifications without FPIR were associated with rates of 6%, 23%, and 66%, whereas those including FPIR were 7%, 26%, and 92%. The authors considered staging of preclinical diabetes an important tool for eventual prevention therapy (4). Received October 20, 1999. Accepted November 12, 1999. Address correspondence and requests for reprints to: Arlan L. Rosenbloom, Department of Pediatrics, Children’s Medical Services Center, 1701 SW 16th Avenue, Room 2163, Gainesville, Florida 32608. 0021-972X/00/$03.00/0 Vol. 85, No. 2 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society