Maternal T1D Protection Requires Intrauterine Exposure: EASD 2026

RESULTS from a new study presented at EASD 2026 confirmed that maternal type 1 diabetes (T1D) confers relative protection against offspring T1D and revealed that protection requires intrauterine exposure to maternal T1D. Results also showed that offspring of parents with type 2 diabetes (T2D) had a lower baseline risk of T1D than offspring of parents with T1D, although this analysis was subject to greater uncertainty.

Maternal Protection Against T1D

There is uncertainty as to why T1D risk is lower in those who have mothers with T1D in comparison to those who have fathers or siblings with T1D. As a result, researchers aimed to understand the relative importance of intrauterine exposure to maternal hyperglycaemia. Specifically, the authors assessed whether relative maternal protection is conferred to offspring in other forms of diabetes and whether maternal protection is only observed in individuals whose mothers were diagnosed before birth.

Two national population-based cohorts comprising 3.8 million livebirths from Sweden and Wales were generated using linked health and population data. Survival analysis compared the cumulative incidence of type 1 diabetes among individuals with affected mothers and those with other first-degree relatives with the same form of diabetes. The impact of parental diagnosis and parental age at diagnosis was explored by the researchers and analyses were adjusted for sex, year of birth, deprivation and maternal characteristics.

Timing of Maternal Diagnosis

The data confirmed lower T1D risk among individuals with mothers with T1D compared with affected fathers or siblings. In Sweden, risk compared with an affected father was lower (adjusted hazard ratio [aHR]: 0.86; 95% CI: 0.77–0.96; p=0.005). Compared with an affected sibling, the association was observed in Wales and Sweden (aHR: 0.56; 95% CI: 0.45–0.70; p<0.001 and aHR: 0.46; 95% CI: 0.40–0.53; p<0.001, respectively).

However, relative maternal protection was observed only when the mother had received a T1D diagnosis before the offspring’s birth. In Sweden, maternal diagnosis before birth was associated with lower risk compared with paternal T1D (aHR: 0.80; 95% CI: 0.70–0.91; p=0.001). Following maternal diagnosis after birth, there was no significant difference (aHR: 1.17; 95% CI: 0.95–1.45; p=0.132).

Implications for T1D Research

Offspring of mothers with T2D or gestational diabetes had a modestly increased risk of T1D in both cohorts. In Sweden, offspring of fathers with T2D also had increased risk. There was no significant difference in T1D risk between individuals with mothers and fathers with T2D (aHR: 1.00; 95% CI: 0.81–1.24; p=0.964).

Overall, the findings suggest that intrauterine exposure to maternal T1D is required for relative maternal protection in offspring. The authors noted that, if larger studies confirm that maternal protection is not associated with maternal T2D, maternal hyperglycaemia is unlikely to be the sole driver of the protective effect.

Reference

Allen A et al. Novel insights into relative maternal protection against offspring type 1 diabetes. Abstract OP100. EASD Congress 28 September-2 October.