In Utero Overnutrition Influences Placental Nutrient Transport and Fetal Overgrowth

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Obesity is defined as a body mass index (BMI) ≥30 kg/m2. Forty-three percent of women of childbearing age are obese, with a greater prevalence noted in Black women. Obesity increases the risk of diabetes (Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM)). Obesity and diabetes are chronic states of overnutrition and metabolic dysregulation, each associated with an increased risk of macrosomia (large weight for gestational age in offspring). Macrosomia not only increases pregnancy complications but also increases the risk of metabolic disorders throughout the lifespan of the offspring. Fetal growth in utero is mediated by the nutritional environment and nutritional transport across the placenta. Maternal-fetal nutrient transport is primarily mediated by placental transporters for glucose, amino acids, free fatty acids, and cholesterol in the syncytiotrophoblast of the placenta. Yet, the mechanistic pathway driving fetal overgrowth in environments of overnutrition are not well defined. Therefore, we will test the hypothesis that diabetes (T2DM or GDM) exacerbates placental nutrient transport and fetal overgrowth in Black pregnant women with obesity. To evaluate the combined influence of obesity and diabetes (T2DM or GDM) on fetal growth, we evaluated n=100 electronic medical records of Black obese women with and without diabetes (T2DM or GDM) from 2012-2022 at the University of Mississippi Medical Center (UMMC). These women were singleton pregnancies with no additional underlying conditions. Gestational age of offspring and maternal age were similar among all groups. This study was approved by the Institutional Review Board at UMMC (IRB-UMMC-2021-0455). We found that Black obese women with diabetes (n=43) had higher BMIs compared to Black women with obesity alone (n=57) (43.50 ± 4.76 kg/m2 vs. 39.19 ± 3.48 kg/m2) (p<0.05), indicating that obesity increases risk of diabetes in Black pregnant women. Additionally, offspring from Black obese women with diabetes had elevated birthweight compared to offspring from women with obesity alone (3345 ± 614.6 g vs. 3099 ± 465.4 g; p<0.05). Male offspring from Black obese women with diabetes had elevated birthweight (3460 ± 695.8 g) compared to female offspring from Black obese women without diabetes (3068 ± 439.8 g) (p<0.05), suggesting the maternal nutritional environment influences males more than females. Yet, the type of diabetes, T2DM or GDM, did not influence birthweight in offspring from Black obese women (T2DM: 3412 ± 743.5 g vs GDM: 3271 ± 439.7 g). To evaluate the influence of obesity plus diabetes on placental nutrient transport, we measured placental protein expression of glucose transporter-1 (Glut-1), a primary glucose transporter in the placenta, in a separate subset of placental tissue from Black obese women with and without diabetes (IRB-UMMC-2019-0058). Protein expression of Glut-1 was increased in placental tissue from Black women with obesity and diabetes (n=4) compared to Black women with obesity alone (n=4) (20.38 ± 5.87 A.U. vs. 9.41 ± 1.46 A.U.; p<0.05). However, BMI was elevated in the group of women with obesity and diabetes compared to obesity alone (49.565 ± 1.39 kg/m2 vs. 43.44 ± 2.44 kg/m2; p<0.05), again indicating that obesity increases risks of diabetes in Black pregnant women. This study indicates that combined obesity with diabetes during pregnancy is associated with increased birthweight and placental protein expression of Glut-1. Additional studies are warranted to decipher the separate influences of elevated BMI and diabetes on fetal growth, along with the associated placental mechanisms that influence nutrient transport and fetal growth in pregnancies complicated by obesity and diabetes. UMMC Department of OBGYN. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.