Immediate Relatives of Patients With T1D Have Increased Individual Risk of T1D, Major Depression, ADHD

Individuals may have increased individual risks of type 1 diabetes (T1D), major depressive disorder (MDD), and attention-deficiency/hyperactivity disorder (ADHD), if they are directly related to somebody with T1D.

Diabetic ketoacidosis (DKA) may play a role in such coaggregation with MDD and ADHD, but further research is needed.

These findings come from a nationwide Taiwanese study published in Acta Diabetologica, which included 24,555 first-degree relatives (FDRs) of individuals with T1D and 98,220 controls matched 1:4 based on age and sex using data from the Taiwan National Health Insurance Research Database between 2001 and 2011.

The study authors used Poisson regression analyses to estimate the risks of MDD, ADHD, and autism spectrum disorder (ASD) among the FDRs.

When adjusted for demographic characteristics, FDRs of at least 1 family member—parents, children, or siblings—with T1D were 46 times more likely to have T1D (adjusted relative risk [ARR], 46.07; 95% CI, 33.36-63.63, P < .001) and 17% more likely to have MDD (ARR, 1.17; 95%CI, 1.04-1.32, P = .009), compared with controls.

When stratified by sex, female FDRs had a 30% increased risk of MDD (ARR, 1.30; 95% CI, 1.13-1.51), while male FDRs had a 21% increased risk of ADHD (ARR, 1.21; 95% CI, 1.01-1.44).

There were also different trends based on relation to the family member with T1D.

Parents of individuals with T1D were 24% more likely to have MDD (ARR, 1.24; 95% CI, 1.06-1.44), while children of individuals with T1D were 41% more likely to have ADHD (ARR, 1.41; 95% CI, 1.11-1.79).

For T1D relative risk specifically, parents, children, and siblings of a family member with T1D were 21.77, 29.01, and 52.19 times more at-risk of having T1D, compared with controls.

Additionally, FDRs of individuals with both T1D and DKA had higher risks of MDD (ARR, 1.35; 95% CI, 1.11-1.64) and ADHD (ARR, 1.40; 95% CI, 1.07-1.82) than controls. However, the authors noted these levels of increased risks were not seen in FDRs of individuals with T1D without DKA.

They also wrote that recent evidence shows no genetic explanation for the association between T1D and MDD. Meanwhile, the relationship between T1D and ADHD is consistent with another meta-analysis, which found preexisting maternal T1D was associated with a 39% increased risk of ADHD in children, and paternal T1D was associated with a 20% increased risk of ADHD in children.

“Future genetic and population-based studies are warranted for better understanding the involvement of genetic and environmental risk factors in clinical manifestations of T1D, MDD, ADHD, and ASD,” the authors noted.

Reference

Hsu TW, Chen MH, Bai YM, et al. Family coaggregation of type 1 diabetes mellitus, major depressive disorder, attention-deficiency hyperactivity disorder and autism spectrum disorder in affected families: a nationwide study. Acta Diabetol. Published online January 13, 2022. doi:10.1007/s00592-022-02025-4