Risk Factors of Gestational Diabetes

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

The overarching goal of this research agenda is to identify risk factors, in particular potentially modifiable factors that may contribute to the prevention of GDM. Research efforts in the past four years include nutritional, environment-chemical, and social-behavioral determinants that are implicated in glucose homeostasis. Within the common theme of insulin resistance and secretion, several important diet and lifestyle associations with GDM have been successfully identified in this effort based on data from the Nurses' Health Study II and the NICHD Fetal Growth Studies. Dr. Zhangs research endeavor in identifying modifiable factors that may contribute to the prevention of GDM. Research efforts in the past four years include nutritional, environment-chemical, and social-behavioral determinants that are implicated in glucose homeostasis. Within the common theme of insulin resistance and secretion, several important diet and lifestyle associations with GDM have been successfully identified in this effort based on data from the Nurses' Health Study II and the NICHD Fetal Growth Studies. Dr. Zhangs research endeavor in identifying modifiable factors of GDM has also integrated emerging new research paradigms on glucose intolerance. For example, a growing body of data highlights the important role of environmental chemicals, such as endocrine disrupting chemicals (EDCs), in the epidemic of metabolic diseases. By altering the endocrine function of organs such as adipose tissue, liver, pancreas, and skeletal muscle, EDCs disrupt the metabolism of carbohydrates and lipids, leading, in turn, to insulin resistance and diabetes. In spite of these leads, studies on environmental chemicals and GDM are very limited. Dr. Zhangs team identified environmentally relevant levels of heavily chlorinated PCBs and some PFAS and PBDEs were positively associated with GDM with suggestive effect modifications by family history of T2D and body adiposity status (Rahman et al. Environ Int 2019). Such findings suggest an environmental etiology for GDM. In addition, Dr. Zhangs team recently began investigating social and behavioral risk factors, for which pregnant women are particularly vulnerable. For example, pregnant women are at high risk for developing depressive symptoms, with at least 10% US women suffering from depression during pregnancy and depression is highly comorbid with diabetes. Data among pregnant women, however, are sparse and prior findings were conflicting. Based on longitudinal assessment of depression during pregnancy, using the NICHD Fetal Growth Studies Cohort, Dr. Zhangs team recently identified that depression early in pregnancy was significantly associated with an increased the risk for GDM and that GDM was strongly associated with an increased risk for postpartum depression (Hinkle et al., Diabetologia 2016). This suggests that depression screening early in pregnancy may be particularly important even among women without a history of mental health conditions. Sleep difficulty is also common among pregnant women. Based on longitudinal assessment of sleep duration during pregnancy, Dr. Zhangs team recently identified a U-shaped relation between 2nd trimester sleep duration and GDM risk, specifically among non-obese women, with the highest risk among women who sleep less than 6 hours (Rawal et al., Am J Obstet Gynecol 2017). However, this increased risk was mitigated among women who napped during the day, revealing an important public health message for pregnant women. Taken together, these findings suggest that in addition to diet and physical activity, as successfully identified in Dr. Zhang's previous research, other social-behavioral factors, such as sleep and depression, are relevant to the development of GDM. In the past year, we also observed that pre-pregnancy habitual folate intake, particularly supplemental folate intake, was inversely associated with risk of GDM (Li et al. Diabetes Care 2019). GDM has substantial burden on the health of mothers and children, and folic acid supplementation among women of reproductive age has been a widely adopted as a, low-cost intervention to reduce neural tube defects and with replication could offer an novel avenue to reduce the risk of GDM. Our research on modifiable risk diet and lifestyle factors in the NICHD Fetal Growth Study demonstrated that greater adherence to three commonly recognized healthful dietary patterns (i.e. Healthy Eating Index, alternate Mediterranean diet, and Dietary Approaches to Stop Hypertension) before and during early pregnancy was related to lower risk of several common pregnancy complications including GDM, pre-term delivery, preeclampsia and gestational hypertension (Li M, et al. American Journal of Clinical Nutrition, 2021). In addition, we demonstrated that achieving moderate-to-vigorous physical activity of at least 760.0 METminweek-1 in early-to-mid 2nd trimester or maintaining at least 500 MET minweek-1 from preconception through 2nd trimester may be related to improved maternal glucose metabolism in the 2nd trimester (McDonald SM, et al. Med Sci Sports Exerc. 2021)