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A type 1 diabetic dad is 1.8 times more likely to pass the condition on to his kids than a type 1 diabetic mom, who, research suggests, confers long-term protection against it. The findings open the door to developing new ways of preventing type 1 diabetes.
In type 1 diabetes (T1D), the body’s immune system attacks the pancreas, resulting in it making little or no insulin. A combination of genetics and environmental factors, such as viruses, is thought to trigger the disease, which usually occurs during childhood but can develop in adults.
Now, a new study, the largest of its kind, led by researchers at Cardiff University and the University of Exeter, both in the UK, has found that children are almost twice as likely to develop T1D when dad has the condition than when mom does. Their results suggest that having T1D while pregnant provides offspring with long-term protection against the condition.
“Individuals with a family history of type 1 diabetes are 8-15 times more likely to develop the autoimmune condition – however, studies have shown the risk is higher if the affected relative is the father rather than the mother,” said Dr Lowri Allen of Cardiff University’s Diabetes Research Group. “Previous studies have suggested that maternal type 1 diabetes is associated with relative protection against type 1 diabetes in offspring during early life. We wanted to know if this relative maternal protection from type 1 diabetes is confined just to childhood.”
The researchers undertook a meta-analysis of five studies containing data about individuals with T1D and their parents. For a total of 11,475 participants diagnosed with T1D between age zero and 88, the researchers compared the proportion who had fathers with the condition versus mothers with the condition. They looked at whether this comparison was affected by age at diagnosis and the timing of the parent’s diagnosis relative to when the child was born. And they compared the genetic risk scores of individuals with type 1 diabetic fathers and mothers, using more than 60 different genes known to be associated with T1D.
The researchers found that people with T1D were 1.8 times more likely to have a dad with T1D than a mom with the condition, regardless of whether the person was diagnosed during childhood or adulthood.
“Taken together, our findings suggest the relative protection associated with having a mother versus father with type 1 diabetes is a long-term effect that extends into adult life,” Allen said.
Insofar as genetic risk testing was concerned, the researchers found that individuals with type 1 diabetic mothers had similar scores to those with type 1 diabetic fathers, suggesting that the protection conferred wasn’t due to inherited genes.
However, the age at which the parents were diagnosed with T1D was important. An individual was more likely to have a father, rather than a mother, with T1D only if the parent was diagnosed before the offspring was born. This means that the protection against T1D conferred by a type 1 diabetic mother was only provided if the mother had the condition during pregnancy.
“This, coupled with the finding that the inherited genetic risk of type 1 diabetes was not different in individuals with affected mothers and fathers, suggests that exposure to type 1 diabetes in the womb is critical,” said Allen. “Further research is needed to determine what it is about exposure to type 1 diabetes in the womb that is more important – is it exposure to high blood glucose levels, insulin treatment, antibodies associated with type 1 diabetes, a combination of these, or exposure to another aspect of type 1 diabetes?”
The information obtained from the study could pave the way for new therapeutic approaches for type 1 diabetics.
“Understanding why having a mother compared with a father with type 1 diabetes offers a relative protection against type 1 diabetes could help us develop new ways to prevent type 1 diabetes, such as treatments that mimic some of the protective elements from mother,” Allen said. “Further research is needed but ultimately, we hope that it might be possible in the future to offer treatments at the very earliest stages of life to prevent the onset of type 1 diabetes in individuals who are at particularly high risk of the disease.”
The study will be presented at the Annual Meeting of the European Association of the Study of Diabetes (EASD), to be held in Spain in September. It has not yet been published or peer-reviewed, but an abstract is available here.