Offspring of women with insulin-dependent diabetes mellitus (IDDM) have a significantly lower risk of IDDM than the offspring of men with IDDM. Furthermore, a negative association of the risk of IDDM in the offspring with maternal age at delivery has been reported. This study tested the association with maternal age in an independent set of families (n = 103) in which the mother had at least one pregnancy before and after the onset of IDDM. In the 304 offspring, the mean ± SE risk of IDDM by age 20 was 6.0 ± 2.4% for those born at maternal ages < 25 yr, whereas, the risk was significantly lower (0.7 ± 0.7%) for those born at older maternal ages (P = 0.03). These 304 offspring were combined with a sample of 1391 offspring previously reported for a multivariate analysis of other factors related to pregnancy (4). In the combined analysis, the risk of IDDM in offspring born at maternal ages > 25 yr was one-fifth that for offspring born to younger mothers. The risk of IDDM in the offspring was not significantly related to birth order, mother's age at first pregnancy, or the interval between pregnancies for subsequent ones. The risk for the children born before the mother's onset of diabetes was higher than that for those exposed in utero to her diabetes, but the difference did not reach statistical significance. In conclusion, although genetic factors are important determinants of susceptibility to IDDM, exposure to maternal diabetes protects offspring from IDDM during the first 2 decades of life. Moreover, a child born to an IDDM mother >25 yr old has an even lower risk than a child born to that mother at a younger age. The combined result is that a child born to a >25-yr-old woman with IDDM has a very low risk of developing IDDM, almost as low as the children of nondiabetic parents. This has immediate practical implications for women with IDDM who are considering pregnancy and important implications for hypotheses regarding the mechanism that underlies the protective effect of exposure to maternal diabetes.

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