Maternal Neudesin Levels in Pregnant Women with Gestational Diabetes Mellitus.

BACKGROUND: Our aim was to investigate the changes in neudesin levels in pregnant women with GDM and the relationship between neudesin and metabolic parameters. METHODS: Forty pregnant women diagnosed with GDM and forty age- and gestational week-matched control subjects were included in the study. Demographic data were obtained from records. Maternal lipid profiles, glucose levels, fasting insulin, HbA1C, and HOMA-IR results were compared between the groups. Correlation tests were performed to evaluate the relationship between neudesin and clinical and laboratory diagnostic parameters. p < 0.05 were interpreted as statistically significant. RESULTS: The human serum neudesin levels were significantly lower in the GDM group compared with the controls. The correlation tests showed statistically negative and weak correlations between the neudesin levels and the maternal age, 50 g OGCT, 100 g OGTT 3 hours, and HbA1C. The optimum neudesin cutoff value for a diagnosis of GDM disease is 6.94 ng/dL, with a sensitivity of 65.9% and a specificity of 63.2%. CONCLUSIONS: This study has shown that lower neudesin levels may occur as a reflection of changes in glucose metabolism during intrauterine life.

Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study.

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators.

BACKGROUND: The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. METHODS: Based on the Ma'anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. RESULTS: From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (ß = 0.40, 95% CI: 0.18 to 0.62, PFDR < 0.001), HbA1c (ß = 0.22, 95% CI: 0.09 to 0.34, PFDR = 0.009), TyG (ß = 0.22, 95% CI: 0.07 to 0.37, PFDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (ß = 2.43, 95% CI: 0.02 to 4.85, PFDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (ß = -0.58, 95% CI: -0.99 to -0.18, PFDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. CONCLUSION: A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.

INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Lipids, apolipoproteins and gestational diabetes mellitus: a Mendelian randomization study.

BACKGROUND: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM. METHODS: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment. RESULTS: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI). CONCLUSION: The study demonstrates a significant causal relationship between apoA-I and GDM risk.

Selenium Supplementation and Gestational Diabetes: A Randomised Controlled Trial.

OBJECTIVE: To assess the effects of selenium supplementation on blood glucose levels in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Internal Medicine, Istanbul Medipol University, Faculty of Medicine, Istanbul, Turkiye, from February to July 2023. METHODOLOGY: In the first phase of this study, the selenium levels of the pregnant women who routinely had an oral glucose tolerance test were measured, and in the second phase of the study, the pregnant women diagnosed with GDM were randomly divided into two groups that received 4-week interventions: Diet alone and diet plus selenium supplementation (200 µg/day). RESULTS: Selenium level in pregnant women with GDM was significantly lower than in healthy pregnant women, and a selenium level less than 80 ng/ml predicted GDM diagnosis with a sensitivity of 58.59% and a specificity of 67.11%. Pregnant women with low selenium (<80 ng/ml) had a 2.709-fold higher risk for GDM compared to those with higher values. Fasting blood glucose levels decreased significantly in both groups after the respective interventions, but the decrease was greater in selenium recipients. Furthermore, fasting, 1st and 2nd hour blood glucose levels were lower in selenium recipients compared to those who only received diet. CONCLUSION: Selenium level in pregnant women with GDM was low compared to healthy pregnant women. Selenium supplementation had a beneficial impact (compared to diet only) on blood glucose levels in pregnant women with GDM. KEY WORDS: Pregnancy, Pregnancy outcome, Diabetes, Gestational, Dietary supplements, Selenium.

Do WHO criteria for gestational diabetes fit a rural population in Tanzania? - A follow-up study assessing mother and child health six years after a pregnancy diagnosed with gestational diabetes.

AIMS AND METHODS: In low- and middle- income countries (LMICs) consequences of gestational diabetes (GDM) is understudied. Using a prospective cohort of mothers (n = 197)and children (n = 251), from rural north-eastern Tanzania, we assessed prediabetes and type 2 diabetes (T2D) prevalence six years after a pregnancy with/without GDM. RESULTS: The prevalence of prediabetes (49.4 % vs. 46.4 %) orT2D (20.0 % vs. 16.1 %), p ≥ 0.36, based on fasting plasma glucose (FPG) or HbA1clevels (prediabetes: 16.9 % vs. 13.8 % and T2D 1.2 % vs. 0 %, p = 0.47), andcardio-metabolic health parameters,weresimilar between women with/without previous GDM. These results were supported by similar perinatal outcomes and child health at follow-up.The overall prevalence ofprediabetes/T2D was high, but no differences in other cardio-metabolic risk markers were observed in women with prediabetes/T2D compared to women with normal glucose tolerance. CONCLUSIONS: Despite high prevalence of GDM amongTanzanian women, the diagnosis was not associated with adverse pregnancy outcomes, nor with increased risk of prediabetes or T2D at follow-up. FPG and HbA1c may be poor markers for diabetes in this population, and further follow-up studies with longer time intervals are warranted to evaluate which GDM diagnostic criteria are most optimal for women in rural Tanzania and similar LMIC settings.

One abnormal value in oral glucose tolerance test during pregnancy and type 2 diabetes risk: Insights from a 5-Year Follow-Up study.

OBJECTIVES: To evaluate the risk of type 2 diabetes(T2D) following one abnormal value(OAbV) in an oral glucose tolerance test(oGTT) performed during pregnancy. STUDY DESIGN: A retrospective analysis of parturients between 01.01.2017 and 31.12.2020 with 5 years of follow-up after delivery. Glucose levels during pregnancy were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes. Women with multiple gestations or pregestational diabetes were excluded. Maternal characteristics and risk of T2D were stratified and compared between 3 groups: normal glucose status, OAbV in oGTT, and gestational diabetes. Statistical analysis included univariate analysis followed by survival analysis. Further analysis was stratified to women with and without obesity. RESULTS: 58,693 women entered the analysis. Following an adjustment to maternal age, obesity, hypertension, and hyperlipidemia, OAbV in oGTT was associated with a 1.8-fold increased risk of T2D in a 5-year follow-up compared to normal glucose status. When stratified by obesity, OAbV was associated with a 3.7-fold increase in T2D in women without obesity, however, was no longer a statistically significant predictor of T2D among women with obesity. CONCLUSIONS: Women with OAbV oGTT during pregnancy are at increased risk for developing T2D over 5 years of follow-up.

Human Cord Blood Endothelial Progenitor Cells and Pregnancy Complications (Preeclampsia, Gestational Diabetes Mellitus, and Fetal Growth Restriction).

Hemangioblasts give rise to endothelial progenitor cells (EPCs), which also express the cell surface markers CD133 and c-kit. They may differentiate into the outgrowth endothelial cells (OECs) that control neovascularization in the developing embryo. According to numerous studies, reduced levels of EPCs in circulation have been linked to human cardiovascular disorders. Furthermore, preeclampsia and senescence have been linked to levels of EPCs produced from cord blood. Uncertainties surround how preeclampsia affects the way EPCs function. It is reasonable to speculate that preeclampsia may have an impact on the function of fetal EPCs during the in utero period; however, the present literature suggests that maternal vasculopathies, including preeclampsia, damage fetal circulation. Additionally, the differentiation potential and general activity of EPCs may serve as an indicator of the health of the fetal vascular system as they promote neovascularization and repair during pregnancy. Thus, the purpose of this review is to compare-through the assessment of their quantity, differentiation potency, angiogenic activity, and senescence-the angiogenic function of fetal EPCs obtained from cord blood for normal and pregnancy problems (preeclampsia, gestational diabetes mellitus, and fetal growth restriction). This will shed light on the relationship between the angiogenic function of fetal EPCs and pregnancy complications, which could have an effect on the management of long-term health issues like metabolic and cardiovascular disorders in offspring with abnormal vasculature development.

Butyrate and iso-butyrate: a new perspective on nutrition prevention of gestational diabetes mellitus.

BACKGROUND: Dietary imbalance, such as a lower proportion of complex carbohydrates and a higher protein diet, may contribute to gestational diabetes mellitus (GDM) risks through their metabolisms. However, there is a lack of knowledge regarding the association between butyrate, iso-butyrate, and GDM, which are metabolisms of the two primary nutrients above. This study aimed to clarify the association of butyrate and iso-butyrate with GDM. METHODS: A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2017 to 2018. Totally, 99 singleton women were involved (GDM: n = 49, control: n = 50). All participants provided blood samples twice (in their first and second trimesters). Gas chromatography-mass spectrometry (GC-MS) was used for butyrate and iso-butyrate detection. Unconditional logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: The results showed that butyrate in the first trimester was negatively correlated with GDM (odds ratio (OR): 0.00, 95% confidential interval (CI): 0.00-0.21, P = 0.008), and iso-butyrate in the second trimester was positively related to GDM (OR: 627.68, 95% CI: 40.51-9724.56, P < 0.001). The ratio (butyrate/iso-butyrate) was negatively associated with GDM, both in the first trimester (OR: 0.00, 95%CI: 0.00-0.05, P < 0.001) and in the second trimester (OR: 0.52, 95% CI: 0.34-0.80, P = 0.003). The area under the curve (AUC) using the ratio in the first trimester combined with clinical risk factors achieved 0.89 (95% CI: 0.83-0.95). Iso-butyrate in the second trimester combined with clinical risk factors achieved an AUC of 0.97 (95% CI: 0.92-1.00). CONCLUSIONS: High iso-butyrate and low butyrate levels may be associated with an increased risk of GDM. As they are produced through dietary nutrient formation by gut microbiota, further studies on the association of dietary intake and butyrate or iso-butyrate concentration in plasma may help find a novel approach to nutritional intervention for GDM.

Association between Toxoplasma gondii and gestational diabetes with regard to serum leptin and tumor necrosis factor alpha, a preliminary study.

Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July-November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii, and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9-21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii, leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers.

The application of plasma circRAD18 in the prediction of gestational diabetes mellitus (GDM) and its adverse effects.

BACKGROUND: In cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects. METHODS: A total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM. RESULTS: After admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress. CONCLUSION: The reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy. AIMS: The study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women's neonates and fetuses born to mothers with GDM. MATERIALS AND METHODS: Cord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit. RESULTS: Fetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age. CONCLUSION: These findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

Establishment of pregnancy-specific lipid reference intervals in pregnant women in a single-centre and assessment of the predictive value of early lipids for gestational diabetes mellitus: a prospective cohort study.

INTRODUCTION: This study was aimed at establishing a pregnancy-specific lipid reference interval (RI) in pregnant women in a single-centre in the Beijing area of China, simultaneously exploring the predictive value of lipid levels in early pregnancy for gestational diabetes mellitus (GDM). MATERIAL AND METHODS: From October 2017 to August 2019, Peking University International Hospital established records for 1588 pregnant women, whose lipid profiles were determined during the first and third trimesters. The Hoffmann technique was used to calculate gestation-specific lipid RI. The 95% reference range for gestational lipids was also estimated for 509 healthy pregnant women screened according to the Clinical and Laboratory Standards Institute guideline. Multivariate logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence interval (CI), and the receiver operating characteristic (ROC) curve was applied to assess the predictive value of lipids in the first trimester for the diagnosis of GDM. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the third trimester (p < 0.05). Hoffmann technique RI of the lipid profiles and the 95% reference range of the lipid profiles in healthy pregnant women did not differ statistically (p > 0.05). TC, TG, and LDL-C levels were higher in the GDM group in the first trimester (p < 0.05), and the risk of GDM was 2.1 times higher in women with higher TG (95% CI: 1.13-3.77, p < 0.05). The optimal ROC cut-off for TG to predict GDM was 2.375 mmol / L, and the area under the ROC curve was 0.622 (95% CI: 0.592-0.751), with a sensitivity of 73.7% and a specificity of 59.3%. CONCLUSIONS: This study established pregnancy-specific lipid RI for pregnant women in a single centre in the Beijing area of China. Pregnant women with TG ≥ 2.375 mmol/L in the first trimester were at significantly increased risk for GDM.

Hypoglycaemia following the 2-hour 75g OGTT in pregnancy - Investigating maternal and foetal outcomes.

AIMS: To investigate differences in maternal and foetal outcomes in pregnancy, where patients developed hypoglycaemia following the 2-hour 75g oral glucose tolerance test (OGTT). METHOD: A retrospective cohort study of 200 pregnancies attending the Antenatal Clinic at Tameside General Hospital between 2018 and 2022. Outcomes were compared between 4 groups: normal OGTT [G1; (n = 39, 20%), diagnosis of gestational diabetes mellitus (GDM) based on OGTT [G2; BG ≥ 5.6 mmol/L or 2-h OGTT ≥7.8 (n = 41, 21%)], hypoglycaemia [G3; 2 h OGTT 3.0-3.9 mmol/L (n = 93, 47%)], or clinically significant hypoglycaemia [G4; 2 h OGTT <3.0 mmol/L (n = 27, 14%)]. Maternal BMI, foetal birth weight (FBW), neonatal complications, neo-natal intensive care unit (NICU) stay and conversion to GDM were assessed. RESULTS: Maternal BMI was lower in G3 and G4 (27.3 kg/m2 and 28.1 kg/m2 respectively) compared to G1 (30.4 kg/m2) (p = 0.02). NICU stay was more frequent in G3 (12%, n = 11) and G4 (8%, n = 2) compared to G1 (5%, n = 2). Foetal complications occurred in 27% of G3 (n = 25) and 33% of G4 (n = 9) compared to 23% in G1 (n = 9) and 17% in G2 (n = 7). FBW was similar in G1 when compared to G3 and G4 (p = 0.34). Of the 120 patients in G3 and G4, 25 patients self-monitored blood glucose for two weeks; 28% (n = 7) subsequently developed GDM. CONCLUSION: Higher rates of NICU stay and foetal complications were seen in both hypoglycaemic groups. In patients with hypoglycaemia following OGTT there is evidence to support self-monitoring blood glucose as 28% were later diagnosed with GDM.

Exposure to gestational diabetes mellitus increases subclinical inflammation mediated in part by obesity.

Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study, we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focussing on elucidating the roles of obesity and GDM to the clinical outcome. Using immunoassays and multicolour flow cytometry, cytokine profiles and immune cell frequencies were measured in maternal circulation and central metabolic tissues [placenta and visceral adipose tissue (VAT)] in GDM-diagnosed (n = 28) and normal glucose tolerant (n = 32) women undergoing caesarean section. Participants were sub-grouped as non-obese [body mass index (BMI) < 30 kg/m2] or obese (BMI ≥ 30 kg/m2). Unsupervised data analysis was performed on the flow cytometry data set to identify functional alterations. GDM obese participants had significantly elevated circulating IL-6 and IL-17A levels. GDM non-obese participants had elevated circulating IL-12p70, elevated placental IL-17A, and VAT IFN-γ production. Unsupervised clustering of immune populations across the three biological sites simultaneously, identified different NK- and T-cell phenotypes that were altered in NGT obese and GDM non-obese participants, while a classical tissue monocyte cluster was increased in GDM obese participants. In this study, there was significant evidence of subclinical inflammation, and significant alterations in clusters of NK cells, T cells, and tissue monocyte populations in GDM. While increased adiposity assimilates with increased inflammation in the non-pregnant state, this overt relationship may not be as evident during pregnancy and warrants further examination in future longitudinal studies.

Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.

Gestational diabetes mellitus (GDM) is considered one of the most common diseases that occur during pregnancy. In addition to increasing the risk of numerous complications throughout gestation, it is also believed to have a long-term potential to impact the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease for the mother and her offspring. While there are clear guidelines for healthy weight gain in pregnancy depending on pre-pregnancy BMI, as well as dietary and training recommendations to achieve this, an increasing number of women are experiencing excessive gestational weight gain (EGWG). Such patients have a higher risk of developing GDM and gestational hypertension, as well as requiring caesarian delivery. Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein that seems to play an important role in glucose metabolism, and inhibition of its activity positively affects glucose regulation. The aim of our study was to compare DPP-4 concentrations in patients with GDM and EGWG with healthy women. DPP-4 levels were assessed in serum and urine samples collected on the day of delivery. The bioelectrical impedance analysis (BIA) method was also used to analyze the body composition of patients on the second day of the postpartum period. DPP-4 serum concentrations were significantly higher in patients in the GDM and EGWG groups compared to healthy women. Urinary DPP-4 concentrations were significantly higher in the control and GDM groups than in the EGWG group. Serum DPP-4 levels were positively correlated with BMI measured before pregnancy, on the delivery day, and in the early postpartum period, among other factors. According to our knowledge, this is the first study to determine DPP-4 levels in EGWG patients. DPP-4 may be related to the occurrence of GDM and EGWG; however, this requires further research.