PREDICTION AND PREVENTION OF TYPE 1 DIABETES
M. Knip
Hospital for Children and Adolescents, University
of Helsinki, Helsinki, Finland
Clinical
type 1 diabetes represents end-stage insulitis resulting from progressive
beta-cell destruction. The knowledge that the clinical manifestation of
diabetes is preceded by an asymptomatic phase that may last for years, and
recent advances in our ability to identify individuals at increased risk of
clinical disease have paved the way for trials aimed at preventing or
delaying the clinical onset of type 1 diabetes. Individuals at increased
disease risk can be identified by a positive family history, or by genetic,
immunological and/or metabolic markers. As long as there is no effective
preventive modality available for clinical use, screening for high-risk
individuals can be considered ethically acceptable only in the context of
sound research protocols. Among the predictive tools available, the
combination of various diabetes-associated autoantibodies seems to provide
a high positive predictive value (PPV) in first-degree relatives, with a
satisfactory sensitivity. The combination of antibodies may also result in
a relatively high PPV in the background population, but there are data
indicating that the most cost-effective screening approach for the general
population is the combination of genetic and autoimmune markers.
Prevention
of type 1 diabetes can be implemented at three different levels. Primary
prevention comprises all strategies aimed at decreasing the incidence of
the disease by reducing the risk of developing diabetes, and targets
subjects without any sign of beta-cell damage. The objective of secondary
prevention is to reduce the incidence of diabetes by stopping ongoing
beta-cell destruction. Tertiary prevention can be initiated after the
clinical manifestation of diabetes, and it aims at restoring beta-cell
function or at preventing secondary complications of the disease. At
present, one primary prevention and three comprehensive secondary prevention
trials are in progress. Common features of the intervention trials are that
the recruitment of subjects fulfilling the inclusion criteria is
time-consuming, and the trials have to last for a long time, as long as
clinical disease is the endpoint. The ongoing prevention trials may,
however, represent a new era of type 1 diabetes - the beginning of the end
of this complicated disease.