Modeling Insulin and Glucose Dynamics and Metabolic Adaptions During Pregnancy under Two Testing Conditions: Oral Glucose Tolerance Test and Hyperinsulinemic-Euglycemic Clamp

Abstract

Background Maternal metabolism has important short- and long-term implications for mothers and their infants. Elevated levels of circulating maternal glucose and insulin are associated with large for gestational age infants and increased neonatal adiposity, both of which can have negative health effects. Assessing maternal glucose and insulin dynamics during pregnancy is important for identifying women in need of intervention and has the potential for informing personalized prenatal care. Methods We developed a novel system dynamics simulation model that estimates plasma insulin and glucose levels in early (12–16 weeks) and late (34–36 weeks) pregnancy under two clinical testing conditions: a 3-hour 75g fasted oral glucose tolerance test, and 3-hr fasted hyperinsulinemic-euglycemic clamp conditions. Results Model output closely resembled research data collected from 28 racially and ethnically diverse participants at both time points (e.g., OGTT glucose R2 in early pregnancy: 0.97, OGTT insulin R2 in early pregnancy: 0.98). The late pregnancy model includes five known metabolic adaptations that occur over the course of gestation, which contribute to the development of maternal insulin resistance. This physiologic insulin resistance in pregnancy facilitates nutrient availability to support fetal growth as gestation progresses. Conclusion This study is an initial step toward developing a personalized tool for monitoring maternal glucose dynamics to improve prenatal care, especially for pregnancies complicated by obesity and/or GDM. The novel simulation model shows how a combination of metabolic adaptations during pregnancy can explain the observed development of insulin resistance the occurs between early to late pregnancy. We included key delays in insulin action, an innovative approach to model glucose intake during an OGTT, and used several testing conditions to inform and validate the model. The model output aligned with plasma insulin and glucose in early and late pregnancy among participants (N = 28) under measured OGTT and simulated hyperinsulinemic-euglycemic clamp conditions.