Review of Genetic and Artificial Intelligence approaches to improving Gestational Diabetes Mellitus Screening and Diagnosis in sub-Saharan Africa.

Background: Adverse outcomes from gestational diabetes mellitus (GDM) in the mother and newborn are well established. Genetic variants may predict GDM and Artificial Intelligence (AI) can potentially assist with improved screening and early identification in lower resource settings. There is limited information on genetic variants associated with GDM in sub-Saharan Africa and the implementation of AI in GDM screening in sub-Saharan Africa is largely unknown. Methods: We reviewed the literature on what is known about genetic predictors of GDM in sub-Saharan African women. We searched PubMed and Google Scholar for single nucleotide polymorphisms (SNPs) involved in GDM predisposition in a sub-Saharan African population. We report on barriers that limit the implementation of AI that could assist with GDM screening and offer possible solutions. Results: In a Black South African cohort, the minor allele of the SNP rs4581569 existing in the PDX1 gene was significantly associated with GDM. We were not able to find any published literature on the implementation of AI to identify women at risk of GDM before second trimester of pregnancy in sub-Saharan Africa. Barriers to successful integration of AI into healthcare systems are broad but solutions exist. Conclusions: More research is needed to identify SNPs associated with GDM in sub-Saharan Africa. The implementation of AI and its applications in the field of healthcare in the sub-Saharan African region is a significant opportunity to positively impact early identification of GDM.

Effect of Prenatal Care on Perinatal Outcomes of Pregnant Women with Diabetes Mellitus: A Systematic Review.

Objective: to evaluate the effect of prenatal care (PC) on perinatal outcomes of pregnant women with diabetes mellitus (DM). Methods: systematic review developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines and conducted through the population, intervention, control, and outcomes (PICO) strategy. Clinical trials and observational studies were selected, with adult pregnant women, single-fetus pregnancy, diagnosis of DM, or gestational DM and who had received PC and/or nutritional therapy (NT). The search was carried out in PubMed, Scopus, and BIREME databases. The quality of the studies was evaluated using the tools of the National Heart, Lung and Blood Institute-National Institutes of Health (NHLBI-NIH). Results: We identified 5972 records, of which 15 (n=47 420 pregnant women) met the eligibility criteria. The most recurrent outcomes were glycemic control (14 studies; n=9096 participants), hypertensive disorders of pregnancy (2; n=39 282), prematurity (6; n=40 163), large for gestational age newborns (4; n=1556), fetal macrosomia (birth weight >4kg) (6; n=2980) and intensive care unit admission (4; n=2022). Conclusions: The findings suggest that PC interferes with the perinatal outcome, being able to reduce the risks of complications associated with this comorbidity through early intervention, especially when the NT is an integral part of this assistance.

Impact of postpartum weight change on metabolic syndrome and its components among women with recent gestational diabetes mellitus.

BACKGROUND: While postpartum weight changes may affect the levels of metabolic parameters, the direct effects of weight changes in the postpartum period on changes in the prevalence rates of metabolic syndrome and its components remain unstudied. This study aimed to investigate the effects of postpartum weight changes between 6 weeks and 6 months on changes in the prevalence rates of metabolic syndrome and its components in women who have recently experienced gestational diabetes mellitus. METHODS: This prospective cohort study included 171 postpartum women with recent gestational diabetes mellitus, who underwent serial weight and metabolic risk factor assessments at 6 weeks and 6 months postpartum. Weight changes between these time points were classified as weight loss (> 2 kg), weight stability (± 2 kg), or weight gain (> 2 kg). Metabolic syndrome comprised the following metabolic risk factors: large waist circumference, elevated blood pressure, elevated fasting plasma glucose levels, high triglyceride levels, and low high-density lipoprotein cholesterol levels. RESULTS: Of the 171 women in our cohort, 30 women (17.5%) lost > 2 kg of body weight, while 85 (49.7%) maintained a stable weight and 56 (32.8%) gained > 2 kg. The weight loss group experienced significant changes in the prevalence rates of the following metabolic risk factors compared to the weight stability and weight gain groups: large waist circumference (% change: - 26.7 vs - 5.9 vs 5.4, respectively; p = 0.004), elevated fasting plasma glucose levels (% change: - 3.4 vs 18.9 vs 26.8, respectively; p = 0.022), and high triglyceride levels (% change: - 30.0 vs 0 vs - 7.2, respectively; p = 0.024). A significantly greater decrease in the prevalence of metabolic syndrome was also found in the weight loss group than in the other two groups (% change: - 20.0 vs 11.8 vs 14.2, respectively; p = 0.002). CONCLUSIONS: Weight changes from 6 weeks to 6 months postpartum significantly altered the prevalence rates of metabolic syndrome and its components in women with recent gestational diabetes mellitus. Early postpartum weight loss can reverse metabolic risk factors and reduce the prevalence of metabolic syndrome. TRIAL REGISTRATION: Thai Clinical Trials Registry: Registration no. TCTR20200903001. Date of registration: September 3, 2020. Date of initial participant enrolment: September 7, 2020.

Metabolic syndrome (MetS) is a frequent diagnosis with consequences for the occurrence of cardiovascular diseases. Women with gestational diabetes mellitus (GDM) are especially vulnerable to the development of MetS. In this study, we investigated how postpartum weight changes, specifically between 6 weeks and 6 months postpartum, impact MetS and its components in women who have recently experienced GDM. The results of our study showed that women who lost > 2 kg of body weight between 6 weeks and 6 months postpartum had significant decreases in the prevalence rates of metabolic risk factors, leading to a lower prevalence of MetS, compared to women who maintained a stable weight (± 2 kg) or gained > 2 kg. Our findings suggest that such weight loss is beneficial for preventing MetS; thus, strategies should be developed to support women with GDM in achieving postpartum weight loss. These strategies may include personalized dietary counseling, exercise programs, and behavioral support tailored to the specific needs and challenges faced by this population.

Imbalance of gut microbiota in gestational diabetes.

AIM: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS: A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS: (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS: Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION: The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).

Effect of Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes among hyperglycemic mothers.

OBJECTIVE: Hyperglycemic mothers and their offspring are at increased risk of various maternal and neonatal complications such as macrosomia, future type 2 diabetes, and metabolic abnormalities. Early diagnosis and individualized dietary management, exercise, and emotional well-being are expected to reduce these risks. The study aims to identify the effect of the Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes of hyperglycemic mothers. PATIENTS AND METHODS: A pre-experimental study was performed among 89 hyperglycemic mothers. Glycemic control at 28 and 36 weeks, weight gain during pregnancy, pre-eclampsia, pregnancy-induced hypertension (PIH), mode of delivery, duration of exercise, emotional well-being, neonates' birth weight, incidence of hypoglycemia, and NICU admission were compared among the study and control groups. The intervention group received an individualized NBMP from their diagnosis of hyperglycemia until delivery. RESULTS: The results showed a significant difference in blood glucose between the study periods and groups at p<0.05 as per repeated ANOVA. Also, diet scores had a significant influence on BMI and glycemic control at p<0.05. Logistic regression models, adjusted for potential confounders including baseline blood glucose, age, economic status, previous GDM, family history of DM as well as baseline BMI, diet score, physical activity, and maternal well-being score, indicated that the NBMP reduced the blood glucose and BMI significantly at p<0.05 in the study group. NBMP also reduced the risk of SGA/LGA and preterm/post-mature birth, as well as increased the exercise duration and emotional well-being of mothers. CONCLUSIONS: The study's conclusions draw attention to the possible roles that maternal wellness, physical activity, and diet may have in reducing risks for both hyperglycemic mothers and their newborns. The NBMP resulted in higher adherence to lifestyle changes. Further research on a larger sample of hyperglycemic mothers is recommended to expand the generalizability of the findings.

Gestational diabetes mellitus enhances cobalt placental transfer efficiency between mother and infant.

Background: The fetal stage is pivotal for growth and development, making it susceptible to the adverse effects of prenatal metal(loid)s exposure. This study evaluated the influence of gestational diabetes mellitus (GDM) on the placental transfer efficiency (PTE) of metal(loid)s and thus assessed the associated risks of prenatal metal(loid)s exposure.Materials and method: Designed as a case-control study, it incorporated 114 pregnant participants: 65 without complications and 49 diagnosed with GDM. We utilized inductively coupled plasma mass spectrometry to quantify seven metal(loid)s - manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), gallium (Ga), arsenic (As), and cadmium (Cd) - in both maternal venous blood and umbilical cord blood.Result: We compared metal(loid)s concentrations and their PTE in the maternal and cord blood between the two groups. Notably, Cu, Ga, As, and Co levels in the umbilical cord blood of the GDM group (657.9 ± 167.2 µg/L, 1.23 ± 0.34 µg/L, 5.19 ± 2.58 µg/L, 1.09 ± 2.03 µg/L) surpassed those of the control group, with PTE of Co showing a marked increase in GDM group (568.8 ± 150.4 µg/L, 1.05 ± 0.31 µg/L, 4.09 ± 2.54 µg/L, 0.47 ± 0.91 µg/L), with PTE of Co showing a marked increase in GDM group (p < 0.05). The PTE of Ni exhibited a reduction in the GDM group relative to the control group, yet this decrease did not reach statistical significance.Conclusion: This study indicates that GDM can influence the placental transfer efficiency of certain metal(loid)s, leading to higher concentrations of Co, Cu, Ga, and As in the umbilical cord blood of the GDM group. The marked increase in the PTE of Co suggests a potential link to placental abnormal angiogenesis due to GDM.

The Impact of Environmental and Occupational Noise on Maternal and Perinatal Pregnancy Outcomes.

Importance: Pregnant women are exposed to both occupational and environmental noise during their pregnancy. The association between noise and adverse health outcomes is well known. Less is known about the relationship between noise and its effects on the embryo/fetus and pregnancy. Objectives: The purpose of the study is to review what is known about the effect(s) of environment and occupational noise during pregnancy on maternal and perinatal outcomes. Evidence Acquisition: Electronic databases (PubMed, CINAHL, and Embase) were searched from 1995-2023 with the only limitation being that the articles were in English. Studies were selected that examined associations between environmental and occupational noise and pregnancy outcome, maternal outcome, or perinatal outcome. Results: There were 233 articles identified. After reviewing all abstracts and selected full texts, 25 publications were used as the basis of this review. Multiple studies have been undertaken evaluating the effects of noise on embryonal/fetal growth, fetal development, maternal hypertension, gestational diabetes, and maternal anxiety and depression. The overall effects of occupational and environmental exposure on both fetal and maternal outcomes remain uncertain. Conclusions: Further high-quality studies are needed to determine the association between noise and pregnancy outcomes. Relevance: Even though this review suggests a relationship between noise and maternal/fetal outcomes, confirmation will require well designed future studies.

Ghrelin regulates the endoplasmic reticulum stress signalling pathway in gestational diabetes mellitus.

OBJECTIVE: We aimed to investigate the effects and mechanisms of the ghrelin-regulated endoplasmic reticulum stress (ERS) signalling pathway in gestational diabetes mellitus (GDM). METHODS: Pregnant female C57BL/6 mice were randomly divided into a normal group, GDM group (high-fat diet + STZ), GDM + ghrelin group (acyl ghrelin), and GDM + ghrelin + ghrelin inhibitor group ([D-lys3]-GHRP-6). We measured body weight, the intake of water and food, glucose, cholesterol, triglyceride and fasting insulin levels in each group. HE staining was used to observe the morphological changes in the pancreas. The TUNEL method was used to detect the apoptosis rate of islet cells. qPCR and Western boltting were performed to detect the relative expression levels of PERK, ATF6, IREIα, GRP78, CHOP and caspase-12, which are related to the ERS signalling pathway in the pancreas. Then, NIT-1 cells were cultured to verify whether ghrelin regulates ERS under high-glucose or tunicamycin conditions. RESULTS: Compared with the GDM group, the GDM + ghrelin group showed improved physical conditions and significantly decreased the fasting blood glucose, glucose tolerance, cholesterol, triglyceride and fasting insulin levels. Damaged islet areas were inhibited by ghrelin in the GDM group. The GDM + ghrelin group showed reduced ß-cell apoptosis compared to the GDM and GDM + ghrelin + ghrelin inhibitor groups. ERS-associated factors (PERK, ATF6, IREIα, GRP78, CHOP and caspase-12) mRNA and protein levels were obviously lower in the GDM + ghrelin group than in the GDM group, while expression levels were restored in the inhibitor group. Ghrelin treatment improved the high-glucose or tunicamycin-induced apoptosis, increased insulin levels and upregulation of GRP78, CHOP and caspase-12 in NIT-1 cells. CONCLUSION: Ghrelin suppressed ERS signalling and apoptosis in GDM mice and in NIT-1 cells. This study established a link between ghrelin and GDM, and the targeting of ERS with ghrelin represents a promising therapeutic strategy for GDM.

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.

Introduction: Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. Methods: Our study investigated the expression of IL-1ß, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome. Results: In T1DM, HBCs showed inflammatory activation characterised by increased IL-1ß and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1ß and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. Conclusion: The expression profiles of IL-1ß, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1ß expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

Efficacy of a phone reminder to improve adherence to post-partum glucose tolerance testing after gestational diabetes and clinical predictors of post-partum follow-up compliance.

AIM: To assess the effectiveness of a phone reminder to improve adherence to post-partum glucose tolerance testing in women with gestational diabetes mellitus (GDM) and to identify clinical predictors of adherence to post-partum follow-up. METHODS: Retrospective study including 543 women with GDM. We assessed the adherence rate to post-partum glucose tolerance testing in women who received a phone reminder (n = 297) compared to women not alerted (n = 246). Demographic and clinical variables were collected to identify the predictors of adherence to the post-partum oral glucose tolerance test (OGTT). RESULTS: The adherence to post-partum OGTT was higher in women who received the phone reminder compared to those not alerted (60.6 % vs. 35.4 %, p < 0.001). Women less compliant compared to those more compliant, had a higher pre-pregnancy body mass index (BMI) (29.3 ± 7.9 vs. 27.0 ± 6.1 Kg/m2, p = 0.03). The adherence was lower in pre-pregnant obese compared to non-obese women (42.7 % vs. 52.0 %, p < 0.05), in women with only one, compared to multiple OGTT alterations during pregnancy (44.5 % vs. 57.8 %, p < 0.05), and in women non-insulin treated compared to those insulin-treated (40.0 % vs. 57.1 % vs, p < 0.001). CONCLUSIONS: The phone reminder improved post-partum follow-up adherence. Pre-pregnancy BMI, number of OGTT alterations and type of therapy could identify poorly adherent women.

Prevalence of gestational diabetes mellitus risk factors in singleton pregnancies obtained by assisted reproductive technology: An observational, retrospective, real-world study from a pregnancy registry.

AIMS: Several studies showed that Assisted Reproductive Technology (ART) could affect gestational diabetes mellitus (GDM) onset. The aim of this study was to estimate the prevalence of GDM risk factors in a cohort of women with singleton pregnancy obtained by ART and complicated by GDM. Maternal and neonatal outcomes were explored. METHODS: We retrospectively collected data of pregnancies of women with singleton pregnancy obtained by ART and complicated by GDM consecutively cared for at a specialized center for diabetes and pregnancy care. Prevalence and combination of GDM risk factors, their combinations and maternal-fetal outcomes were estimated. RESULTS: Overall, our cohort included 50 women (mean age of 40.4 ± 4.7 years, mean pre-pregnancy BMI 26.3 ± 6.2 kg/m2). The most frequent GDM traditional risk factors were age ≥ 35 years (94 %), family history of diabetes (44 %), overweight (29 %) and obesity (19 %). Combining risk factors, 5 groups were identified with 1, 2, 3, 4, or 5 risk factors with a prevalence respectively of 28 %, 46 %, 20 %, 4 %, and 2 %. Examining features of the above groups, pre-pregnancy weight (p < 0.0001) and pre-pregnancy BMI (p < 0.0001) statistically significant differed in the 5 groups, increasing with higher numbers of risk factors. Regarding neonatal outcomes only neonatal hypoglycemia (p = 0.03) differed significantly among the groups, with higher percentages in women with higher numbers of combined risk factors. CONCLUSION: Prevalence of GDM traditional risk factors in singleton ART pregnancies complicated by GDM is considerable. Such pregnancies need appropriate clinical attention because of the risk of adverse outcomes.

Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes-a prospective cohort study in Shanghai.

OBJECTIVES: The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs). DESIGN: This was a prospective cohort study. SETTING: This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China. PRIMARY AND SECONDARY OUTCOME MEASURES: A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model. RESULTS: The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP. CONCLUSIONS: As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

Transition of the genital mollicutes from the second to the third trimester of pregnancy and its association with adverse pregnancy outcomes in GDM women: a prospective, single-center cohort study from China.

BACKGROUND: The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. METHODS: We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. RESULTS: Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. CONCLUSION: Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.

Neonatal outcomes according to different glucose threshold values in gestational diabetes: a register-based study.

BACKGROUND: Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. METHODS: This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1-5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8-8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality - was analysed using multivariate logistic regression. RESULTS: The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71-1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60-1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27-0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18-0.57). DISCUSSION: The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.

Lactation duration and development of type 2 diabetes and metabolic syndrome in postpartum women with recent gestational diabetes mellitus.

BACKGROUND: The World Health Organization and United Nations Children's Fund recommend exclusive breastfeeding (EBF) for the first six months of an infant's life. Although evidence suggests that maintaining breastfeeding has positive impacts on glucose and lipid metabolism in postpartum women with a history of gestational diabetes mellitus (GDM), no study has investigated whether such effects differ between breastfeeding intensities. This study aimed to evaluate the impact of maintaining breastfeeding on prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) six months postpartum in women with GDM. This study also examined the potential variations in glucometabolic outcomes between EBF at six months and partial breastfeeding at six months. METHODS: This prospective cohort study included 130 women with recent GDM who experienced live births between 7 September 2020 and 31 January 2023 at a university hospital in Bangkok, Thailand. All the women were free of T2DM and MetS at baseline (six weeks postpartum). We followed up these women six months postpartum to assess their breastfeeding practices (EBF at six months, partial breastfeeding at six months, or not maintaining breastfeeding) and evaluate their progression to prediabetes, T2DM, and MetS. Maintaining breastfeeding was defined as breastfeeding for six months. EBF was determined using the "recall since birth" method. RESULTS: Of the 130 participants included, the rates of prediabetes, T2DM, and MetS six months postpartum were 33% (n = 43), 2% (n = 3), and 17% (n = 22), respectively. In the unadjusted model, maintaining breastfeeding was associated with a reduction in the risks of prediabetes and MetS but not T2DM. After adjusting for potential confounders, maintaining breastfeeding was a significant protective factor only for prediabetes. The adjusted risk ratios and 95% confidence intervals were 0.54 (0.29, 0.99) for prediabetes and 0.47 (0.19, 1.06) for MetS. When EBF at six months and partial breastfeeding at six months were separately analyzed, the risks of prediabetes and MetS differed between the two groups. In the EBF at six months-to-partial breastfeeding at six months comparison, the adjusted risk ratios (95% confidence intervals) of prediabetes and MetS were 0.46 (0.22, 0.97) vs. 0.79 (0.25, 2.49) and 0.34 (0.11, 0.99) vs. 0.69 (0.22, 2.07), respectively. CONCLUSIONS: Maintaining breastfeeding reduced the risk of prediabetes and MetS, but not of T2DM, six months postpartum; these effects were significant only with EBF. These findings indicate that supporting maternal efforts to practice EBF for six months may improve women's health after GDM. TRIAL REGISTRATION: Thai Clinical Trials Registry Registration No. TCTR20200902003. Date of registration: September 2, 2020. Date of initial participant enrollment: September 7, 2020.

MicroRNA Associations with Preterm Labor-A Systematic Review.

This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial pregnancy complication. Covering studies disseminated from 2018 to 2023, the review integrates discoveries from diverse pregnancy-related scenarios, encompassing gestational diabetes, hypertensive disorders and pregnancy loss. Through meticulous search strategies and rigorous quality assessments, 47 relevant studies were incorporated. The synthesis highlights the transformative potential of microRNAs as valuable diagnostic tools, offering promising avenues for early intervention. Notably, specific miRNAs demonstrate robust predictive capabilities. In conclusion, this comprehensive analysis lays the foundation for subsequent research, intervention strategies and improved outcomes in the realm of preterm labor.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin. Their availability can be modulated within the islet by pericyte-mediated regulation of microvascular blood flow. Within the islet, both endocrine progenitor cells and the ability of endocrine cells to trans-differentiate between phenotypes can alter endocrine cell mass to adapt to changed metabolic circumstances, regulated by the within-islet trophic environment. Optimal islet function is precariously balanced due to the high metabolic rate required by beta-cells to synthesize and secrete insulin, and they are susceptible to oxidative and endoplasmic reticular stress in the face of high metabolic demand. Resulting changes in paracrine dynamics within the islets can contribute to the emergence of Types 1, 2 and gestational diabetes.