PREVENTION OF IDDM - THE GENETIC EPIDEMIOLOGIC PERSPECTIVE

Rational prevention of insulin-dependent diabetes mellitus (IDDM) requ ires knowledge about the aetiology and pathogenesis of the disease. Th e causation of IDDM is complex, involving genetic susceptibility as we ll as non-genetic determinants. The evidence of a genetic component to IDDM is based on the high concordance rate in monozygotic twins as co mpared with dizygotic twins, the higher recurrence risk among relative s of patients with IDDM as compared with the general population risk, and the well-established associations with genetic markers, including specific alleles from the HLA-locus. The evidence of a non-genetic com ponent to IDDM is primarily based on the fact that the concordance rar e in monozygotic twins is far from unity; the huge geographical variat ion in the incidence of IDDM, even between genetically similar populat ions, and the increasing incidence in many populations provide further support: associations between the risk of developing IDDM and exposur e to several non-genetic determinants, including nutrients and viral i nfections, have been established and serve as additional evidence. In general, the relative risks conferred by the non-genetic determinants are rather small, and it is unknown how these factors initiate the aut oimmune-mediated process that destroys the beta-cells of the pancreas. Recent findings suggest that non-genetic factors interact with geneti c susceptibility genes in the causation of IDDM. Firstly, it appears t hat the increase in the incidence of IDDM has predominantly been obser ved in populations with high frequency of susceptibility genes. Second ly, it seems that the risk of IDDM among relatives of patients with ID DM is positively correlated with the general population risk level. Al l these lines of evidence considered together suggest that IDDM may de velop from several different combinations of susceptibility genes acti ng together with non-genetic exposures. If so, prevention of IDDM will require assessment of disease risk at individual rather than at popul ation level. Since genetic screening is neither feasible nor ethically acceptable in the population at large, possible prevention of IDDM wi ll be restricted to individuals who, by means of a positive family his tory, may be classified as being at high disease risk.