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Age at Onset of Type 1 Diabetes in Parents and Recurrence Risk in Offspring
Authors:Valma Harjutsalo   Niina Lammi   Marjatta Karvonen     Per-Henrik Groop
Affiliation:1Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum Helsinki, Helsinki, Finland; ;2Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; ;3National Institute of Health and Welfare, Diabetes Prevention Unit, Helsinki, Finland.
Abstract:

OBJECTIVE

Our aim was to study the recurrence risk of type 1 diabetes in the offspring of parents with adult-onset (15–39 years) type 1 diabetes and to evaluate the transmission of diabetes within a continuum of parental age at onset of diabetes from childhood to adulthood.

RESEARCH DESIGN AND METHODS

Diabetes status of all offspring (n = 9,636) in two Finnish cohorts of parents with type 1 diabetes was defined until the end of year 2007. Cumulative incidences of type 1 diabetes among the offspring were estimated, and several factors contributing to the risk were assessed.

RESULTS

During 137,455 person-years, a total of 413 offspring were diagnosed with type 1 diabetes. The cumulative incidence by 20 years was 4.0% (95% CI 3.1–4.8) for the offspring of parents with adult-onset diabetes. The risk was equal according to the sex of the parents. The cumulative incidence decreased in parallel with the increase in age at onset of diabetes in the fathers. In the offspring of diabetic mothers, the risk was equal regardless of the age at onset of diabetes. However, the reduced risk in the maternal offspring was most pronounced in the daughters of the mothers with a diagnosis age <10 years.

CONCLUSIONS

Type 1 diabetes transmission ratio distortion is strongly related to the sex and age at onset of diabetes in the diabetic parents.Type 1 diabetes can occur at any age, although it is predominantly seen in children and young adults. Therefore, the majority of studies have been conducted in children aged <15 years. The recurrence risk in the offspring ranges from 3 to 6% depending on the study design, follow-up time, and the population where the study was conducted (13). Little is known about the recurrence risk in first-degree relatives of subjects diagnosed with type 1 diabetes, aged >15 years. The incidence of type 1 diabetes is much lower in young adults than in children (46). Consequently, the risk of family members may also be different among the diabetic subjects affected after childhood.Sex-related factors seem to be involved in the transmission of diabetes from one generation to the next (7). By 20 years of age, 5–8% of the offspring of diabetic men and only 2–5% of the offspring of diabetic women have been found to be affected (13,8). We have previously shown that the recurrence risk of diabetes in the offspring of parents diagnosed between 0–17 years of age was higher the younger the father was when diagnosed with type 1 diabetes. This pattern was not present in the offspring of the mothers (8). However, it is not known whether the sex-related factors play a role in the transmission of diabetes in adult-onset type 1 diabetes. We have now enlarged our study to also include the offspring of parents diagnosed with diabetes between 15 and 39 years of age. This gives us an opportunity to determine the risk in the offspring of parents with a broad age span at diagnosis and to elucidate whether there are differences in the risk between the offspring of diabetic mothers and fathers.
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