Empirical Risk for Insulin-dependent Diabetes (IDD) in Sibs: Further Definition of Genetic Heterogeneity

Abstract

We have studied the effect of age at diagnosis in the proband and parental status [normal versus non-insulin-dependent diabetes (NIDD)] on the cumulative risk to age 40 (CR40) for insulin-dependent diabetes (IDD) in sibs of IDD probands in 493 families. We found a significantly increased cumulative risk to age 40 for IDD in sibs of probands with disease diagnosed before age 10 (8.5 ± 2.0%) as compared with that in sibs of probands with disease diagnosed after age 10 (4.6 ± 0.8%) (×2 = 7.6, P = 0.006). Within the family subset with probands of earlier IDD onset (before age 10) we also found an increased CR40 for IDD in the sibs of the probands in families with an NIDD parent (with NIDD parent: CR40 = 24.7 ± 10.7%; with normal parents: CR40 = 7.5 ± 2.0%, ×2 = 12.8, P < 0.0005). These data are compatible with the theory of heterogeneity (genetic and/or environmental) of IDD and a possible relationship between IDD and NIDD.