Differential Transmission of Type 1 Diabetes from Diabetic Fathers and Mothers to Their Offspring

Abstract

We studied the incidence of type 1 diabetes in the offspring of patients with childhood- and adolescent-onset type 1 diabetes and several risk factors predicting the risk. We defined the diabetes status in the offspring of all probands who were included in the nationwide register of Finnish type 1 diabetic patients diagnosed at the age of ≤17 years from 1965 to 1979. A total of 5,291 offspring at risk contributed 72,220 person-years of follow-up between 1970 and 2003. Of them, 259 offspring developed type 1 diabetes by the end of 2003, giving a cumulative incidence of 6.7% (95% CI 5.9–7.5) by the age of 20 years. The incidence of type 1 diabetes in the offspring between the years 1980 and 2003 was 35.3, 44.6, and 44.6 per 10,000 person-years for the age-groups 0–4, 5–9, and 10–14 years, respectively. Poisson regression analyses showed a marked increase in incidence of 5.3% per year from 1983 to 2003. The greatest increase occurred in the youngest offspring, aged 0–4 years. Of the offspring of male probands, 7.8% were affected by the age of 20 years compared with 5.3% of the offspring of female probands (relative risk 1.7 [95% CI 1.3–2.2]). The young age at onset of diabetes increased the risk of type 1 diabetes in the offspring of diabetic fathers but not in the offspring of diabetic mothers. In conclusion, our findings revealed that in the offspring of type 1 diabetic patients, the increase in the recurrence risk of type 1 diabetes was not more rapid compared with that in the background population. In the multivariate analyses, statistically significant predictors of type 1 diabetes in the offspring were male sex of the diabetic parent, young age at diagnosis in the male parent, and the more recent year of birth of the offspring.