Children more likely to inherit type 1 diabetes from fathers than mothers

The child of a father with type 1 diabetes (T1D) is nearly twice as likely to develop the condition compared to if the mother has it, according to a press release and abstract ahead of the European Association for the Study of Diabetes (EASD) meeting taking place in Madrid from September 9-13, 2024.¹

The study data, to be presented at EASD, suggests T1D exposure in the womb confers long-term protection against the condition in children of affected mothers.¹

"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. We wanted to understand this more," said lead researcher Lowri Allen of the Diabetes Research Group, Cardiff University, Cardiff, United Kingdom.¹

Allen and colleagues performed a meta-analysis spanning 5 cohorts of patients with T1D (n = 11,475) diagnosed at age 0 to 88 years, and compared the proportion with affected fathers and mothers. The investigative team sought to determine if the comparison was altered by age at diagnosis and timing of parental diagnosis relative to offspring birth. T1D genetic risk scores (GRS2) between individuals with mothers and fathers with T1D were compared.²

“Previous studies have suggested that maternal type 1 diabetes is associated with relative protection against type 1 diabetes in offspring during early life," said Allen. "We wanted to know if this relative maternal protection from type 1 diabetes is confined just to childhood. We were also interested in what might be responsible for the effect.”

Results demonstrated that individuals with T1D were 1.8 times more likely to have a father with T1D compared to a mother with the condition (overall OR 1.79) (95% CI, 1.59, 2.03 [P < 0.0001]). The proportion of individuals with an affected father compared to an affected mother was higher among individuals diagnosed at younger than 18 years of age (OR 1.64) (95% CI 1.14, 2.37 [P < 0.0001]), and among those aged 18 years and older (OR 1.80) (95% CI, 1.58, 2.05 [P < 0.0001]).²

An excess of individuals with affected fathers was only observed if parental diagnosis was before offspring birth (OR 1.92) (95%CI 1.30,2.83 [P =0 .001] vs OR 1.28) (95% CI 0.94, 1.75 [P = 0.12 after birth]).²

"Age at diagnosis and type 1 diabetes-free survival curves were comparable amongst offspring of affected fathers and mothers (P = 0.31, 0.94 respectively)," the investigators wrote in an online abstract. "GRS2 was not significantly different between individuals with affected fathers versus mothers (P = 0.31)."²

"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," said Allen.

The GRS2 takes into account more than 60 different genes known to be associated with T1D. The investigators noted timing of the diagnosis was important, as the individual was only more likely to have a father with T1D, rather than a mother, if the parent was diagnosed before the individual was born.

"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.

In conclusion, Allen added, "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."

References:

1. Type 1 diabetes passes to kids from dads more than mums. Scimex. July 27, 2024. Accessed July 29, 2024. https://www.scimex.org/newsfeed/type-1-diabetes-passes-to-kids-from-dads-more-than-mums
2. Maternal type 1 diabetes confers long-term relative protection against type 1 diabetes in the offspring: results from five cohort studies. Abstract 32. To be presented at: European Association for the Study of Diabetes. Madrid. September 9-13, 2024.