Our study employing Mendelian Randomization (MR) demonstrates a robust correlation between asthma and elevated rates of gestational diabetes mellitus (GDM), indicating an enhanced vulnerability to GDM in individuals with asthma. This investigation introduces an innovative use of MR to evaluate how asthma affects GDM probabilities. The findings advocate for intensified surveillance and management of expectant mothers with asthma in their medical care.
Reinforcing this perspective, a body of existing research, encompassing observational studies and systematic analyses, validates our observations, underscoring the definitive association between asthma prevalence and GDM manifestation. It is established that asthma sufferers face a 25–40% heightened risk of contracting GDM[21–24]. Specifically, one study highlights that asthma-afflicted women are at an increased risk for GDM, with an Odds Ratio (OR) of 3.82 and a 95% Confidence Interval (CI) ranging from 1.06 to 13.75[25].
The association between asthma and an increased likelihood of developing Gestational Diabetes Mellitus (GDM) is still not clearly understood. This connection is believed to stem from multiple factors, including the state of being overweight or experiencing significant weight gain during pregnancy, alterations in the levels of adipokines and inflammatory agents, as well as low vitamin D levels[26]. Research shows that women with asthma during pregnancy tend to have higher Body Mass Index (BMI) values, making them more prone to GDM as their BMI increases[27, 28]. Additionally, asthmatic individuals are found to have different concentrations of adipokines and inflammatory indicators, such as leptin and interleukin (IL)-6, in contrast to those without asthma[29–31]. An increase in leptin and TNF-α levels may worsen inflammation, potentially leading to greater insulin resistance[32]. Adipokines influence insulin resistance, β-cell dysfunction, and the distribution and storage of fat within the body, which in turn affects glucose/insulin metabolism and raises the risk of GDM[33].
Vitamin D's contributions extend beyond skeletal well-being, significantly affecting insulin management by enhancing its production, improving signal transduction and sensitivity, and modulating insulin-like growth factor activities for glucose regulation[34, 35]. It directly impacts β-cell functionality, which results in increased insulin secretion[36]. Studies have shown a correlation between asthma sufferers and lower circulating levels of 25(OH)D[37]. This reduced vitamin D status in individuals with asthma might be associated with a higher occurrence of GDM, stemming from compromised insulin synthesis and subsequent rise in blood sugar levels.
This study offers numerous benefits. It stands out for utilizing Mendelian Randomization Analysis to explore the possible direct relationship between asthma and GDM risk, ensuring our results remain clear of confounding factors and reverse causation issues. The extensive use of GWAS datasets enhances the precision of our effect size estimations, outperforming analyses that rely on singular datasets or small-scale studies. The implementation of diverse sensitivity checks further solidifies the credibility of our findings, effectively minimizing bias linked to pleiotropic influences.
This study recognizes specific limitations. Our examination was narrowly focused on individuals of European descent, which may limit the relevance of our findings across different ethnic populations. Additionally, there was significant statistical variability in the methodologies employed, likely due to the differential effects of specific SNPs on the outcomes.