BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls.
METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking.
RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA.
CONCLUSIONS: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies.

Previous studies showed that women with gestational diabetes mellitus (GDM) are susceptible to cognitive dysfunction. We investigated the effects of GDM on brain pathologies and premature brain aging in rats. Seven-week-old female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) after two weeks of acclimatization. On pregnancy day 0, HFD-treated rats received streptozotocin (GDM group) or vehicle (Obese mothers). ND-treated rats received vehicle (ND-control mothers). On postpartum day 21, brains and blood were collected. The GDM group showed increased inflammatory and premature aging markers, mitochondrial changes, and compensatory increases in the blood-brain barrier and synaptic proteins in the prefrontal cortex and hippocampus. GDM triggers maternal brain inflammation and premature aging, suggesting compensatory mechanisms may protect against these effects.

OBJECTIVE: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research.
RESULTS: Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1 year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6 years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

To discuss the correlation between serum progesterone, glycosylated Hemoglobin (HbA1c), and insulin levels in pregnant women with Gestational Diabetes Mellitus (GDM) and the risk of Premature Rupture of Membranes (PROM).
A retrospective analysis was conducted on 52 patients diagnosed with GDM who also presented with PROM (Observation group) and compared with 89 patients diagnosed with GDM but not complicated with PROM (Control group). Progesterone, insulin, and HbA1c were detected. Risk factors for PROM in GDM patients were analyzed.
The observation group had higher HbA1c and fasting blood glucose levels. Poor blood glucose control and GWG are risk factors for PROM in GDM patients. PROM increases adverse pregnancy outcomes in GDM. HbA1c, insulin, and HOMA-IR can predict the risk of PROM in GDM.
The effective prediction of preterm PROM can be achieved through the monitoring of serum HbA1c, insulin levels, and insulin resistance in patients with GDM.

OBJECTIVE: We aimed to evaluate the heterogeneity of gestational diabetes mellitus (GDM) patients diagnosed with various screening criteria.
METHODS: We stratified pregnant women using consecutive fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (2hPPG) intervals of 0.2 mmol/L. The incidence of abnormal neonatal birthweight and birth-related adverse outcomes was compared with that of pregnant women without GDM.
RESULTS: The study included 39,988 pregnant women (18-45 years, mean [SD], 31.5 [4.7] years) in Ningbo, China. The means (SDs) of FPG and 2hPPG within 24-28 weeks of gestation were 4.5 (0.5) and 6.8 (1.3) mmol/L, respectively. A total of 3025 (7.6%) women had 5.1-6.9 mmol/L FPG and 4560 (11.4%) had 8.5-11.0 mmol/L 2hPPG. The incidence of GDM according to the two combination criteria was 17.3% (6908 cases). The relative risk (RR) for < 10th percentile birthweight (< 10th WT) was 0.82 (95% CI, 0.74-0.91, p < 0.001) by 5.1 mmol/L FPG criterion and 1.14 (95% CI, 1.06-1.23, p < 0.001) by 8.5 mmol/L 2hPPG criterion, while the RRs for > 90th percentile birthweight (> 90th WT) were 1.48 (95% CI, 1.35-1.63, p < 0.001) and 0.95 (95% CI, 0.86-1.04, p = 0.29) according to the corresponding criteria. The FPG criterion was more strongly associated with maternal hypertension than the 2hPPG criterion. Both criteria did not show a distinct association with other composite adverse outcomes.
CONCLUSIONS: High FPG is significantly associated with high birth weight, whereas high 2hPPG is slightly associated with low birth weight. Our findings highlight the heterogeneity of patients with GDM diagnosed by different criteria.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

OBJECTIVE: Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship.
METHODS: 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis.
RESULTS: In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475-2.625; P < 0.001). Restricted cubic spline analyses showed a linear relationship between UA and GDM when UA exceeded 222 µmol/L. GDM and UA levels maintained a statistically significant positive correlation in different stratified regression analyses (P < 0.001). However, no evidence of a causal relationship between uric acid and GDM was found by MR analyses with an OR of 1.06 (95% CI: 0.91-1.25) per unit increase in UA.
CONCLUSIONS: There is a positive correlation between UA levels in early pregnancy and the subsequent risk of developing GDM. However, no genetic evidence was found to support a cause-effect relationship between UA and GDM.

UNASSIGNED: Pregnancy-associated fulminant type 1 diabetes (PF) occurs during pregnancy or within 2 weeks of delivery. Although it occurs infrequently, it is associated with high fetal mortality rate. Few studies have examined whether PF is associated with gestational diabetes mellitus (GDM).
UNASSIGNED: A 29-year-old woman diagnosed with GDM at 24 weeks of gestation developed a fever, sore throat, nausea and vomiting at 29 weeks of gestation. Ketoacidosis was considered based on her blood ketone and glucose levels and the results of a blood gas analysis. Since the patient\'s islet function declined rapidly, fluid replacement, insulin therapy, and other treatments were administered. The patient was ultimately diagnosed with PF, and has required ongoing insulin therapy. She delivered a healthy baby girl by elective cesarean section at 37-week gestation. Her blood glucose has been satisfactorily controlled over the 12 months since her acute presentation.
UNASSIGNED: PF is characterized by poor maternal and infant outcomes and a high stillbirth rate. Blood glucose should be regularly monitored in pregnant women with GDM. A sudden increase in blood glucose may indicate the possibility of PF, which needs to be managed in a timely manner to avoid adverse pregnancy outcomes.

Hyperglycemia in pregnancy due to pre-existing Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) is rising globally with increasing rates of risk factors for metabolic disease. This review summarizes current evidence and recommendations from national and international guidelines for diagnosis and management of T2DM and GDM to optimize maternal and neonatal outcomes.

BACKGROUND: Pregnant women with gestational diabetes mellitus (GDM) experience higher psychological stress levels than healthy pregnant women. The objectives of the current study were to examine (1) the differences in anxiety, depression, stress, and somatization levels between women diagnosed with GDM and healthy pregnant women, and (2) the differences in anxiety, depression, stress, and somatization levels among women with well-controlled blood sugar levels compared to those who are not well controlled.
METHODS: A quantitative cross-sectional study was conducted, involving 103 women who had been pregnant at least once, including 40 women diagnosed with GDM and 63 healthy pregnant women. An online questionnaire was distributed that included three parts: socio-demographic parameters, the DASS-21 questionnaire assessing anxiety, depression, and stress, and the Brief Symptom Inventory (BSI) questionnaire assessing somatization.
RESULTS: Differences in the anxiety (t = 14.470, <0.001), depression (t = 8.17, <0.001), stress (t = 16.354, <0.001), and somatization (t = 13.679, <0.001) levels between women diagnosed with GDM and healthy pregnant women were found. Women diagnosed with GDM reported higher levels of anxiety, depression, stress, and somatization compared to those without GDM. Additionally, women with better blood sugar control, as indicated by lower glycated hemoglobin (HbA1c) levels had lower anxiety (t (38) = -2.04, p < 0.05), depression (t(38) = -2.88, p < 0.01), stress (t(38) = -1.88, p < 0.05), and somatization (t(38) = -1.88, p < 0.05) levels compared to women with poorer blood sugar control.
CONCLUSIONS: Pregnant women diagnosed with GDM report higher levels of negative mental health conditions such as anxiety, depression, stress, and somatization compared to healthy pregnant women.