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

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%) (ײ = 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%, ײ = 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.