DECREASED RISK OF TYPE-I DIABETES IN OFFSPRING OF MOTHERS WHO ACQUIREDIABETES DURING ADRENARCHY

Fathers with type I diabetes transmit diabetes to their offspring 2-3 times more frequently than mothers with type I diabetes. This phenomen on has provoked both genetic and nongenetic hypotheses, but the mechan ism remains obscure. We find that mothers who develop diabetes before age 8 transmit diabetes at the same rate as diabetic fathers, and that the sex difference in diabetes transmission is explained by a decreas ed transmission rate in mothers who acquired diabetes after age 8. We constructed a data base containing 2156 nondiabetic and diabetic offsp ring of parents with type I diabetes. Families were selected from our main data base, which contains demographic information and diabetes au toantibody test results on >8000 first-degree relatives of patients wi th type I diabetes and diabetic probands. Identification of offspring was made through diabetic parents who had participated in our autoanti body screening program at the Joslin Diabetes Center between 1983 and 1990. Questionnaires were sent to all other family members to determin e the number of diabetic and nondiabetic offspring in each family. The 20-yr life-table risk of diabetes in offspring of diabetic fathers an d mothers is 8.9 +/- 1.0 and 3.4 +/- 0.6%, respectively. For mothers a cquiring diabetes before or after age 8, the risk of diabetes in offsp ring is 13.9 +/- 4.4 and 2.4 +/- 0.6% at 20 yr of age, respectively. F urthermore, we find that duration of diabetes in mothers before pregna ncy has no effect on the risk of diabetes in their offspring. The incr eased transmission rate of diabetes in diabetic fathers is explained b y a decreased transmission rate of diabetes in mothers who acquire dia betes after age 8. Because women acquiring diabetes after age 8 transm it less diabetes to their offspring, we propose that adrenarchy may ha ve an apparent protective effect on diabetes transmission. We speculat e that mothers who acquire diabetes after age 8 are more susceptible t o this disorder (similar to susceptibility to other organ-specific aut oimmune diseases) and may possess and transmit fewer genetic susceptib ility determinants to their offspring.