Objective: This study aimed to investigate the relationship between maternal blood glucose levels during pregnancy and neonatal birth outcomes in Northwest China. Methods: This population-based cohort study included 10,010 first-trimester pregnant women who joined the birth cohort of the Northwest Women’s and Children’s Hospital from July 2018 to July 2020. Basic demographic characteristics, lifestyle and behavior patterns were collected. Oral glucose tolerance test (OGTT) results during the second trimester and pregnancy outcomes after childbirth were also collected. A generalized linear model was constructed to analyze the effects of blood glucose levels on neonatal birth outcomes. Results: We found that every 1 mmol/L increase in fasting plasma glucose (FPG) was associated with an increase in birth weight (β = 100.22 g, 95% confidence interval (95%CI): 81.91, 118.52), birth weight Z score (β = 0.23, 95%CI: 0.19, 0.27) and birth weight Z centile (β = 6.72%, 95%CI: 5.51, 7.94). Moreover, the risk of macrosomia, premature birth and being born large for gestational age (LGA) increased by 2.01 (95%CI: 1.67, 2.43), 1.35 (95%CI: 1.09, 1.66) and 1.80 (95%CI: 1.57, 2.07) times, respectively. Additionally, for every 1 mmol/L increase in FPG associated with a decrease in gestational age (β = −0.12 weeks, 95%CI: −0.19, −0.06), the risk of SGA decreased by 0.70 (OR = 0.70, 95%CI: 0.55, 0.89) times. Every 1 mmol/L increase in 1/2-h PG had similar outcomes as FPG, besides premature birth and SGA. Conclusions: Higher blood glucose in pregnant women may increase neonatal birth weight, decrease gestational age and lead to a higher risk of macrosomia, premature birth and LGA. Mothers should actively prevent and control hyperglycemia to promote maternal and infant health.

Gestational diabetes mellitus (GDM) is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal mal-development. The deficit and dysfunction of insulin secreting β-cells are signature symptoms for GDM. Pancreatic progenitors derived from human embryonic stem cells (hESCs) were shown to be able to effectively treat diabetes in mice. In this study, we first identified that microRNA-410 (miR-410) directly targets lactate dehydrogenase A (LDHA), a gene selectively repressed in normal insulin secreting β-cells. hESCs that can be induced to express miR-410 hence keeping LDHA levels in check were then differentiated in vitro into pancreatic endoderm, followed by transplantation into db/+ mouse model of GDM. The transplant greatly improved glucose metabolism and reproductive outcome of the pregnant females suffering from GDM. Our findings describe for the first time the method of combining miRNA with hESCs, providing proof of concept by employing genetically modified stem cell therapy for treating GDM.

Purpose: To study the risk factors of gestational diabetes mellitus (GDM) heterogeneity, and to evaluate the correlation between the risk factors and obesity. Methods: We performed a case–control study of 452 women with GDM and 516 women with normal glucose tolerance (NGT) at the first and second trimester. We defined GDM women as GDM-resistance subtype, GDM-dysfunction subtype, and GDM-mixed subtype, according to their simultaneous insulin-release test with predominant insulin-sensitivity defect, insulin-secretion defect, or both defects. Results: We found that higher maternal age, family history of diabetes, the elevated level of fasting blood glucose in the first trimester (≥ 5.1 mmol/L) were risk factors of all GDM subtypes. Pre-pregnancy overweight/obesity and the increased gestational weight gain (GWG) in the first-trimester are risk factors of the GDM-resistance subtype. Indicators including younger age at first menstruation, the elevated levels of alanine aminotransferase (ALT), total bile acid (TBA), triglyceride (TG), and the decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors of the GDM-resistance subtype. However, the associations between those risk factors and GDM-resistance subtype attenuated after adjusted by pre-pregnancy body mass index (pre-BMI) and gestational weight gain (GWG) in the first trimester. Nonalcoholic fatty liver disease (NAFLD) and the improved level of TG are independent risk factors for the GDM-resistance subtype and the GDM-mixed subtype, respectively. Conclusion: Women with GDM exhibited heterogeneity based on glycemic physiology and their risk factors are not all the same. Some obesity-related risk factors are specific to the GDM-resistance subtype, which are mediated by pre-pregnancy overweight/obesity and the elevated GWG the first-trimester.

Background: Evidence showed possible benefits of a less gestational weight gain (GWG) than the US Institute of Medicine (IOM) recommendation in gestational diabetes mellitus (GDM) pregnancy. Here, we aimed to explore an appropriate GWG range in GDM women according to adverse pregnancy outcomes. Methods: We enrolled all the singleton GDM pregnant women (n = 14,213) from January 2015 to December 2018 in Xi'an, Northwest China. According to the pre-pregnancy body mass index (BMI), they were classified into the Underweight (< 18.5 kg/m²), Normal weight (18.5–24.9 kg/m²⁾, Overweight (25.0–29.9 kg/m²) and Obesity (≥ 30.0 kg/m²) group, respectively. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI). The appropriate ranges of GWG were determined based on a significant protective association (OR < 1). Results: Totally, 12,712 participants were finally recruited. There were 1180 (9.3%), 9134 (71.9%), 2097 (16.5%), and 301 (2.4%) patients in the Underweight, Normal weight, Overweight, and Obesity groups, respectively. Adverse outcomes increased with the elevation of pre-pregnancy BMI. Among them, the risk of cesarean section was the highest, followed by large for gestational age (LGA), small for gestational age (SGA), preeclampsia, and gestational hypertension. Through the analysis of the risk of adverse outcomes in continuous GWG categories in each group, an ideal GWG range obtained in this study was as follows: 10–15.9 kg, 8–11.9 kg, 6–7.9 kg, and -5–3.9 kg for the Underweight, Normal weight, Overweight and Obesity group, respectively. Furthermore, the ranges in this study were more protective for adverse outcomes than those from IOM. Conclusions: Based on the adverse pregnancy outcomes of over 12 thousand participants, our findings showed a more stringent GWG range for GDM women than the IOM criteria recommendation.

Objective: To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)–induced macrosomia, term nondiabetic macrosomia, and normal pregnancies. Methods: Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively. Results: The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs. 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion: Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.