The role of night shift work in metabolic disorders during and after pregnancy

夜班工作在怀孕期间和之后代谢紊乱中的作用

The role of night shift work in metabolic disorders during and after pregnancy (I. Agarwal, Project Lead) Gestational diabetes (GDM) is a large and growing epidemic resulting in significant morbidity and mortality to both mothers and babies. GDM is a major risk factor for type II diabetes (T2DM), increasing the risk by 7-fold. Factors that influence the risk of developing T2DM among women with a history of GDM are not well understood. One emerging hypothesis is that circadian misalignment, or inappropriately timed sleep, may influence the risk of GDM and subsequent T2DM. Night shift work, an extreme form of circadian misalignment, has been consistently associated with a higher risk of T2DM in cross-sectional and prospective cohort studies. Limited and conflicting data exist on the relationship of night shift work with GDM. My central hypothesis is that night shift work increases the risk of GDM, and risk of progression from GDM to T2DM. I will test this hypothesis using serially-collected longitudinal data from the national Nurses’ Health Study (NHS) 2 and 3 cohorts. The NHS contains detailed information on sociodemographic, clinical, reproductive, occupational, and lifestyle variables, prospective measurement of incident clinical outcomes including T2DM over a median of 25 years of follow-up (NHS2), and hair and plasma biospecimens from a sub-cohort of pregnant women (NHS3). Overall, the NHS is one of the most comprehensive, prospective longitudinal studies of its kind, and provides unique opportunities to address important research questions. The aims of this project are to: Specific Aim 1. Investigate night shift work as a modifiable risk factor for GDM, and test whether night shift work is associated with stress-related and inflammatory biomarkers measured in early pregnancy. If night shift work is associated with early pregnancy biomarkers, these could be used for risk-stratification, or as sub-clinical biological endpoints in future interventional trials. Specific Aim 2. Determine the relationship between post-pregnancy night shift work and risk of progression from GDM to T2DM. This aim will investigate whether night shift work among high-risk women with a history of GDM increases the risk of progression to T2DM. The proposed research is an integral component of my career development and is tailored to complement my training activities. It will enable me to launch a successful career as an independent researcher with expertise in shift work and metabolism. Furthermore, it addresses an important public health issue and will inform future research including potential interventional studies to lower rates of GDM and subsequent T2DM.