Type 1 diabetes represents less than 5% of the total cases of diabetes globally, but it is one of the most common chronic diseases of childhood [3]. In contrast to many other health outcomes, several large cohort studies suggested that exposure to maternal smoking may decrease the risk of type 1 diabetes in the offspring [4,5,6], although this was not confirmed by all studies [7]. However, observational studies are limited by issues of potential confounding. The observed inverse association between MSDP and offspring risk of type 1 diabetes in cohort studies is prone to bias due to unmeasured confounders, such as shared genetic and early life environmental factors within families. These factors are frequently correlated with MSDP to influence offspring health outcomes.
To control for potential confounders from unmeasured familial background factors, apart from a traditional cohort study design, Wei et al. [8] used a family-based, nested case-control study by matching children with type 1 diabetes to their siblings and cousins who were free of diabetes. Sibling and cousin comparisons are quasi-experimental designs, which use design features to help minimise confounding effects from genetic and environmental factors that are shared by family members [9]. The study by Wei et al. included about three million children born in Sweden between 1983 and 2014 and followed them until 2020. The overall proportion of children exposed to MSDP in this study population was high, with a prevalence of 15.7%. The study found that children exposed to MSDP had a 22% (95% CI: 18%, 25%) reduced risk of developing type 1 diabetes during childhood compared to their unexposed siblings. Similar association was observed in cousin comparison analysis (odds ratio: 0.72, 95% CI: 0.66–0.79) as well as in cohort analysis (hazard ratio: 0.78, 95% CI: 0.75–0.82). For comparison purpose, the authors also reported the association between MSDP and offspring type 2 diabetes using the same study designs. The findings showed that there was an increase in risk of type 2 diabetes in children exposed to MSDP in cohort analysis, but this association was attenuated to null in sibling analysis, indicating confounding effects of unmeasured familial factors. Mechanisms through which MSDP influences type 1 diabetes in the offspring are not clear and needs further investigation. One possible explanation is the immunosuppressive effects of nicotine, which may prevent the development of autoimmune diseases, such as type 1 diabetes, by promoting anti-inflammatory processes.