Effects of maternal type 1 diabetes and confounding factors on neonatal microbiomes.

AIMS/HYPOTHESIS: Body niche-specific microbiota in maternal-neonatal dyads from gravidae with type 1 diabetes have not been quantitatively and functionally examined. Similarly, the impact of pregnancy-specific factors, such as the presence of comorbidities known to occur more frequently among gravidae with type 1 diabetes, including Caesarean delivery, as well as antibiotic prophylaxis, level of glycaemic control during each trimester of pregnancy and insulin administration, has not been adequately considered. The aims of this study were to characterise the maternal and neonatal microbiomes, assess aspects of microbiota transfer from the maternal microbiomes to the neonatal microbiome and explore the impact of type 1 diabetes and confounding factors on the microbiomes. METHODS: In this observational case-control study, we characterised microbiome community composition and function using 16S rRNA amplicon sequencing in a total of 514 vaginal, rectal and ear-skin swabs and stool samples derived from 92 maternal-neonatal dyads (including 50 gravidae with type 1 diabetes) and in-depth clinical metadata from throughout pregnancy and delivery. RESULTS: Type 1 diabetes-specific microbiota were identified among gravidae with type 1 diabetes and their neonates. Neonatal microbiome profiles of ear-skin swabs and stool samples were established, indicating the taxa more prevalent among neonates born to mothers with type 1 diabetes compared with neonates born to control mothers. Without taking into account the type 1 diabetes status of mothers, both delivery mode and intrapartum antibiotic prophylaxis were found to have an influence on neonatal microbiota composition (both p=0.001). In the logistic regression analysis involving all confounding variables, neonatal ear-skin microbiome variation was explained by maternal type 1 diabetes status (p=0.020) and small for gestational age birthweight (p=0.050). Moreover, in women with type 1 diabetes, a relationship was found between HbA1c levels >55 mmol/mol (>7.2%) measured in the first trimester of pregnancy and neonatal ear-skin microbiota composition (p=0.008). In the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) assessment, pathways concerning carbohydrate biosynthesis were predicted as key elements of the microbial functional profiles dysregulated in type 1 diabetes. Additionally, in SourceTracker analysis, we found that, on average, 81.0% of neonatal microbiota was attributed to maternal sources. An increase in the contribution of maternal rectum microbiota and decrease in the contribution of maternal cervix microbiota were found in ear-skin samples of vaginally delivered neonates of mothers with type 1 diabetes compared with neonates born to control mothers (83.2% vs 59.5% and 0.7% vs 5.2%, respectively). CONCLUSIONS/INTERPRETATION: These findings indicate that, in addition to maternal type 1 diabetes, glycaemic dysregulation before/in the first trimester of pregnancy, mode of delivery and intrapartum antibiotic prophylaxis may contribute to the inoculation and formation of the neonatal microbiomes. DATA AVAILABILITY: The BioProject (PRJNA961636) and associated SRA metadata are available at http://www.ncbi.nlm.nih.gov/bioproject/961636 . Processed data on probiotic supplementation and the PICRUSt analysis are available in the Mendeley Data Repository ( https://doi.org/10.17632/g68rwnnrfk.1 ).

Physical activity, gestational weight gain in obese patients with early gestational diabetes and the perinatal outcome - a randomised-controlled trial.

BACKGROUND: Excessive gestational weight gain, especially among women with gestational diabetes, is associated with several adverse perinatal outcomes. Our study aimed to analyse the impact of the use of pedometers to supervise physical activity on maternal health and the obstetric outcomes of pregnant women with obesity and early gestational diabetes. METHODS: 124 pregnant patients were enrolled in the presented research. INCLUSION CRITERIA: singleton pregnancy, age > 18 years, gestational diabetes diagnosed in the first half of pregnancy (< 20th week of pregnancy), obesity according to the American Endocrine Society criteria. Each patient was advised to take at least 5000 steps daily. Patients were randomly assigned to pedometers (N = 62), and were recommended to monitor daily the number of steps. The group without pedometers (N = 62) was not observed. Visit (V1) was scheduled between the 28th and 32nd gestational week (GW), and visit (V2) occurred between the 37th and 39th GW. Anthropometric measurements and blood samples were collected from all patients at each appointment. Foetal and maternal outcomes were analysed at the end of the study. RESULTS: In the group supervised by pedometers, there were significantly fewer newborns with macrosomia (p = 0,03). Only 45% of patients satisfied the recommended physical activity guidelines. Patients who walked more than 5000 steps per day had significantly higher body weight at baseline (p = 0,005), but weight gain was significantly lower than in the group that did not exceed 5000 steps per day (p < 0,001). The perinatal outcome in the group of patients performing more than 5000 steps did not demonstrate significant differences with when compared to less active group. ROC curve for weight gain above the guidelines indicated a statistically substantial cut-off point for this group at the level of 4210 steps/day (p = 0.00001). CONCLUSIONS: Monitoring the activity of pregnant patients with gestational diabetes and obesity by pedometers did not have a significantly impact on their metabolic control and weight gain. However, it contributed to less macrosomia. Furthermore, physical activity over 5,000 steps per day positively affects weight loss, as well as contributes to improved obstetric and neonatal outcomes.

Pathophysiology of Pre-Eclampsia-Two Theories of the Development of the Disease.

Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the pathomechanisms of PE, the pathophysiology of the disease is still not fully understood. While the "two-stage model" of the development of PE is the most widely accepted theory, stating that the placenta is the main source of the disease, there are some other pathophysiological models of PE. Among these other theories, the one considering heart dysfunction as serving as the primary cause of PE seems to be gaining increasing prominence. In this review, we aim to elucidate these two divergent concepts concerning the development of PE. Despite some differences in their proposed pathomechanisms, both theories share vital pathophysiological elements in common. A central and critical component in both models is impaired placental perfusion, which appears to be a crucial phenomenon in PE. A comprehensive understanding of the different pathomechanisms involved in PE may be helpful in clinical practice, prompting a more individual approach to care of patients with PE.

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

BACKGROUND: Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG. METHODS: We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes. RESULTS: In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10-4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10-4) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort. CONCLUSIONS: Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

The Role of the Adipokines in the Most Common Gestational Complications.

Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.

Diagnosis and Management of IUGR in Pregnancy Complicated by Type 1 Diabetes Mellitus.

This review discusses available literature on the diagnosis and management of intrauterine growth restriction (IUGR) in women with type 1 diabetes. IUGR is diagnosed when ultrasound-estimated fetal weight is below the 10th percentile for gestational age. IUGR diagnosis implies a pathologic process behind low fetal weight. IUGR in pregnancy complicated by type 1 diabetes is usually caused by placental dysfunction related to maternal vasculopathy. Prevention of IUGR should ideally start before pregnancy. Strict glycemic control and intensive treatment of nephropathy and hypertension are essential. Low-dose aspirin initiated before 16 gestational weeks can also reduce IUGR risk in women with vasculopathy. Umbilical and uterine artery Doppler studies can guide diagnosis and surveillance of fetuses with IUGR. Decisions regarding the timing of delivery should be based on assessment of umbilical artery Doppler. The risk of prematurity and impaired fetal lung maturation should always be considered, especially in fetuses younger than 32 weeks.

The role of free triiodothyronine in pathogenesis of infertility in levothyroxine-treated women with thyroid autoimmunity - a preliminary observational study.

INTRODUCTION: The aim of this study was to analyze the possible role of free triiodothyronine (FT3) in infertility and in levothyroxine-treated (LT4) euthyroid women with Hashimoto thyroiditis (HT). METHODS: It is an observational retrospective case control study. Twenty one euthyroid women with HT on LT4 replacement therapy and a medical history of idiopathic infertility were included into the study. To achieve higher FT3 level, the dose of LT4 was increased in every patient. Fifteen fertile women with HT on LT4 replacement therapy served as a control group. RESULTS: At baseline in the study group mean thyroid stimulating hormone (TSH) level was 1.96 µU/ml ± 0.84 µU/ml and mean FT3 was 4.07 pmol/l ± 0.78 pmol/l. The mean TSH level after the increase of LT4 was 0.60 µU/ml ± 0.45 µU/ml (p < 0.0001), and the mean FT3 was 5.12 pmol/l ± 0.77 pmol/l (p = 0.0001). Baseline TSH in the study group was higher than in controls (p < 0.0001) and baseline FT3 in the study group was lower than in controls (p = 0.0003). CONCLUSIONS: Relatively low levels of FT3 in women with HT on LT4 replacement therapy may contribute to higher infertility rates.

Insulin resistance in pregnancy complicated by type 1 diabetes mellitus. Do we know enough?

Insulin resistance (IR) is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization. In recent years the increasing role of IR in the pathogenesis of type 1 diabetes mellitus (T1DM) related complications has been taken into account. The aim of this article is to discuss the possible role of IR in pregnancy complicated by T1DM. At the moment, there is no doubt that IR is not only frequently observed in T1DM patients, but also is a separate risk factor of several complications in nonpregnant patients. The role of IR in pregnancy complicated by T1DM has not been widely studied yet. However, data from the studies on different populations showed that IR may predispose to such conditions as miscarriage, preeclampsia and macrosomia. Interestingly all of these are more frequently diagnosed in women with T1DM in comparison to healthy subjects. The literature on the role of IR in human pregnancy is relatively rich. However despite its significance in pathophysiology of T1DM and its complications in general population, there is a lack of understanding of how it affects maternal and fetal health in pregnancy complicated by this disease. Nonetheless, based on the available literature, IR may be proposed as an additional factor modifying pregnancy outcome in woman with T1DM. Therefore, measures that might reduce IR such as good glycemic control and control of weight gain should be recommended for every woman with T1DM, optimally when planning but also throughout the pregnancy

Maternal serum placental growth factor and fetal SGA in pregnancy complicated by type 1 diabetes mellitus.

AIM: To analyze the role of maternal placental growth factor (PlGF) in the prediction of small for gestational age (SGA) birth weight in pregnancy complicated by type 1 diabetes mellitus (T1DM). METHODS: A prospective observational study on 59 normotensive T1DM pregnant women, assessing maternal PlGF concentrations between the 10th-14th and 22nd-25th weeks of gestation. RESULTS: Number of SGA vs. non-SGA newborns was 11 (18.6%) vs. 48 (81.4%), respectively. First trimester PlGF serum concentrations (pg/mL) were similar between SGA vs. non-SGA groups [data given as median (interquartile range)]: 65.5 (35.58-159.20) vs. 68.23 (11.59-150.03), respectively; P=0.44. A trend for lower PlGF concentrations was observed in the second trimester in the SGA vs. non-SGA group: 63.34 (12.79-119.16) vs. 116.75 (33.93-235.82); P=0.07. In the SGA group, PlGF concentrations did not differ between the first and the second trimester: 65.5 (35.58-159.20) vs. 63.34 (12.79-119.16), respectively; P=0.36. In the non-SGA group, PlGF concentrations were significantly higher at the gestational age of 22-25 weeks compared to 10-14 weeks [116.75 (33.93-235.82) vs. 68.23 (11.59-150.03); P=0.03). CONCLUSIONS: Decreased PlGF serum concentration in mid-pregnancy, as well as a lack of physiological increase in PlGF levels between early and mid-gestation, may precede development of SGA in women with T1DM.

Functional analysis of daily glycemic profiles and excessive fetal growth in pregnant patients with well-controlled type 1 diabetes: Retrospective cohort.

AIMS: The study objective was to compare daily glycemic profiles throughout gestation between the mothers of large-for-gestational-age (LGA) and non-LGA newborns in patients with type 1 diabetes (T1D). METHODS: We selected 102 eligible pregnant women who were treated with sensor-augmented pumps in our single-center retrospective cohort study. We used functional data analysis to compare glycemic control across gestation. RESULTS: Median HbA1c values in the first, second, and third trimester were 6.23 %, 5.49 %, and 5.75 % respectively. Median time-in-range (TIR) exceeded 70 % in each trimester (72.4 %, 72.5 %, and 75.9 %, respectively). From 59 % up to 77 % of women met the criteria for well-controlled T1D defined by the mean HbA1c and TIR in each trimester. Despite that, 27 % (28/102) of pregnancies were complicated by LGA. Mothers of LGA infants had significantly increased HbA1c levels and decreased TIR values in the second and third trimesters. The most significant differences in daily mean glucose values between LGA and non-LGA newborns' mothers occurred between 26 and 32 weeks of pregnancy. These discrepancies were noted in daytime glucose values rather than nocturnal and fasting glucose levels. CONCLUSIONS: Mothers of LGA newborns present significantly worse glycemic control. Our findings may emphasize the need for more rigorous daytime glycemic control.

Continuous glucose monitoring parameters in pregnancy-related complications in patients with type 1 diabetes: a retrospective cohort study.

INTRODUCTION: Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). OBJECTIVES: The primary study objective was to analyze associations between numerous novel CGM parameters and neonatal complications, such as large­for­gestational­age (LGA) neonates, hypoglycemia, hyperbilirubinemia, transient breathing disorders, preterm births, as well as pre­eclampsia. PATIENTS AND METHODS: In this single­center retrospective cohort study, we recruited 102 eligible pregnant women with T1D who were treated with sensor­augmented pumps with suspend­before­low function from the first trimester. The pregnant patients were admitted for at least 1 control hospital visit in each trimester of gestation for anthropometric and laboratory measurements and collection of sensor data. RESULTS: The median (interquartile range) percentage values for glycated hemoglobin (HbA1c) (first trimester, 6.23 [5.91-6.9]; second trimester, 5.49 [5.16-5.9]; third trimester, 5.75 [5.39-6.29]) and for time­in­range (first trimester, 72.4 [67.3-80.3]; second trimester, 72.5 [64.7-79.6]; third trimester, 75.9 [67.1-81.4] met the criteria of well­controlled T1D in each trimester of pregnancy. Nonetheless, we noted 27% of LGA births, 25% of neonatal hypoglycemia, 33% of hyperbilirubinemia, and 13% of preterm births. Worse glycemic control and more glycemic fluctuations in the second and third trimesters were mainly associated with increased risk of LGA at birth, transient breathing disorders, and hyperbilirubinemia. CONCLUSIONS: CGM parameters (mean of daily differences, high blood glucose index, glycemic risk assessment in diabetes equation, or continuous overall net glycemic action) in the patients with T1D are significantly associated with the increased risk of LGA at birth and neonatal transient breathing disorders and hyperbilirubinemia. However, we did not find evidence that novel CGM indices could be more effective in predicting those events than the commonly used CGM parameters or HbA1c levels.

Seasonal Pattern in Gestational Diabetes Mellitus in Poland: A Retrospective Cohort Study.

The existing literature does not address the question of the seasonal impact on pregnancy in Central-Eastern Europe; therefore, this study was designed to investigate the seasonal variation in gestational diabetes mellitus (GDM) based on a recent Polish sample. The data of 30,205 newborns from singleton pregnancies and their mothers, including the date and gestational age of birth, neonatal sex and weight, maternal age and parity, mode of delivery, ethnicity, and a detailed list of comorbidities (including GDM), were retrospectively analysed. The prevalence of GDM was significantly (p < 0.0001) lower in spring (14.71%) than in the other seasons (16.78%). A higher incidence of GDM was observed for mothers who underwent an oral glucose tolerance test from June to August compared to those who were tested from December to February (17.34% vs. 14.75%, p < 0.0001). Similarly, there were significant differences between seasons with higher and lower insolation. The regression analysis revealed that seasonal patterns were significantly associated with the prevalence of GDM. In conclusion, this large retrospective cohort study demonstrated seasonal changes in GDM risk. The observed seasonal patterns may equally refer to mothers of babies born at term and prematurely. Further research concerning GDM risk and other seasonal and gender associations is warranted.

BabyNet＋＋: Fetal birth weight prediction using biometry multimodal data acquired less than 24 hours before delivery.

Accurate prediction of fetal weight at birth is essential for effective perinatal care, particularly in the context of antenatal management, which involves determining the timing and mode of delivery. The current standard of care involves performing a prenatal ultrasound 24 hours prior to delivery. However, this task presents challenges as it requires acquiring high-quality images, which becomes difficult during advanced pregnancy due to the lack of amniotic fluid. In this paper, we present a novel method that automatically predicts fetal birth weight by using fetal ultrasound video scans and clinical data. Our proposed method is based on a Transformer-based approach that combines a Residual Transformer Module with a Dynamic Affine Feature Map Transform. This method leverages tabular clinical data to evaluate 2D+t spatio-temporal features in fetal ultrasound video scans. Development and evaluation were carried out on a clinical set comprising 582 2D fetal ultrasound videos and clinical records of pregnancies from 194 patients performed less than 24 hours before delivery. Our results show that our method outperforms several state-of-the-art automatic methods and estimates fetal birth weight with an accuracy comparable to human experts. Hence, automatic measurements obtained by our method can reduce the risk of errors inherent in manual measurements. Observer studies suggest that our approach may be used as an aid for less experienced clinicians to predict fetal birth weight before delivery, optimizing perinatal care regardless of the available expertise.

Adropin in pregnancy complicated by hyperglycemia and obesity - a preliminary study.

OBJECTIVES: According to the data, approximately 33-37% of women of reproductive age are obese. These numbers are reflected in the increasing number of complications in pregnancy, including gestational diabetes. The study aims to assess the concentrations of adropin in the course of gestational diabetes and their possible relationship with the occurrence of obstetric complications characteristic for it. MATERIAL AND METHODS: The study included 65 obese and overweight pregnant patients (BMI > 27 kg/m²) with glycemic disorders diagnosed during pregnancy. Blood samples we collected during visits: V0 - the first half of pregnancy V1 - 28-32 weeks of gestation, and V2 - 37-39 weeks of gestation. The concentrations of adropin were measured during V1 and V2 by ELISA tests. We analyzed the studied patients' anthropometric, metabolic parameters and obstetrical results. RESULTS: In the study group, at the visit V1, the mean level of adropin was 525.5 mmol/mL and 588.1 mmol/mL for the V2 visit. The comparison of adropin concentration between visits showed a statistically significant increase (p = 0.02). The concentration of adropin did not differ between obese and morbidly obese patients at V1, but at V2, there was a significant lover adropin level in morbidly obese patients. CONCLUSIONS: In overweight and obese pregnant patients with gestational diabetes, the levels of adropin in serum increased significantly in the last trimester of pregnancy. The increase in concentration was significantly lower in the morbidly obese patients than in the obese group. The study provides the basis for further analyses of the role of adropin in pregnancies complicated by obesity and gestational diabetes.

Fetomaternal Expression of Glucose Transporters (GLUTs)-Biochemical, Cellular and Clinical Aspects.

Several types of specialized glucose transporters (GLUTs) provide constant glucose transport from the maternal circulation to the developing fetus through the placental barrier from the early stages of pregnancy. GLUT1 is a prominent protein isoform that regulates placental glucose transfer via glucose-facilitated diffusion. The GLUT1 membrane protein density and permeability of the syncytial basal membrane (BM) are the main factors limiting the rate of glucose diffusion in the fetomaternal compartment in physiological conditions. Besides GLUT1, the GLUT3 and GLUT4 isoforms are widely expressed across the human placenta. Numerous medical conditions and molecules, such as hormones, adipokines, and xenobiotics, alter the GLUT's mRNA and protein expression. Diabetes upregulates the BM GLUT's density and promotes fetomaternal glucose transport, leading to excessive fetal growth. However, most studies have found no between-group differences in GLUTs' placental expression in macrosomic and normal control pregnancies. The fetomaternal GLUTs expression may also be influenced by several other conditions, such as chronic hypoxia, preeclampsia, and intrahepatic cholestasis of pregnancy.

Markers of Maternal Insulin Resistance and Lipid Ratios Measured in Early Pregnancy Are Related to Adverse Fetomaternal Outcomes in Women Treated for Hyperglycemia Detected in Early Pregnancy-Data from a Retrospective Cohort Study.

Background: Hyperglycemia detected in early pregnancy is still inadequately studied as a risk factor for adverse maternal and neonatal outcomes. Methods: a retrospective study of a cohort of N = 193 women in singleton pregnancies with hyperglycemia diagnosed before the 20th gestational week (GW). Results: characteristics of the study group: GW at the diagnosis: 12.0 (9.0; 15.0), diabetes diagnosed in early pregnancy (eDiP): 21%, insulin-therapy required: 61.8%, gestational hypertension/preeclampsia: 7.7%, premature delivery: 9.2%, composite adverse neonatal outcome: 59.2%, high (LGA) birth weight/low (SGA) birth weight according to the WHO growth charts: 24.2%/9.2%, respectively. Women with eDiP have lower eGDR, a higher TAG/HDL ratio, and a higher atherogenic index of plasma (AIP) compared to women with gestational diabetes diagnosed in early pregnancy­eGDM (9.33 ± 1.56 vs. 7.92 ± 2.54, p = 0.007, 1.06 ± 0.78, vs. 1.25 ± 0.68, p = 0.020, and −0.06 ± 0.25 vs. 0.04 ± 0.23 p = 0.021, respectively). NonHDL/HDL cholesterol ratio > 2.6, and AIP > 0.24 total/HDL cholesterol ratio > 4.5 significantly predicted metabolic adverse neonatal outcome (hypoglycemia and/or hyperbilirubinemia)­OR (95% CI): 4.62 (1.35; 15.79), 3.60 (1.04; 12.48), 8.75 (1.02; 74.83), respectively. Conclusions: 1, Hyperglycemia diagnosed in early pregnancy coexists with a lipid profile suggestive of insulin resistance. 2, Lipid-related markers of cardiometabolic risk measured in early pregnancy can be useful tools in assessment of fetomaternal risk in high-risk populations. 3, Women with eDiP present a more severe insulin resistance phenotype than those with eGDM.

Novel Continuous Glucose Monitoring Metrics and Large-for-Gestational-Age Risk: An Exploratory Retrospective Cohort Study in Pregnancies with Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). We aimed to assess the between-group differences in glycated hemoglobin (HbA1c) and the incidence of large-for-gestational-age (LGA) neonates in CGM and glucometer users and analyze the potential association of novel CGM metrics with LGA risk in T1D pregnancies. Materials and Methods: Our retrospective study cohort included 134 women with T1D treated with insulin pumps-75 of them used CGM and 59 patients measured their glucose concentrations using glucometers only. As part of our study, we matched the CGM users and patients who preferred the self-monitoring of blood glucose (SMBG) according to their baseline HbA1c and White's diabetes class at a 1:1 ratio. After the matching, both groups included 42 pregnancies. Results: We did not find any difference in changes in HbA1c and perinatal outcomes between CGM and SMBG users; however, we achieved a limited statistical power, and there were more cases of diabetic nephropathy in the SMBG group. Mothers of LGA infants had higher first-trimester HbA1c, time above target, and mean glucose concentrations in each trimester of pregnancy. Other CGM metrics reflecting glucose fluctuations attributed to hyperglycemia were associated with an increased risk of LGA. Despite optimal maternal HbA1c, 39% of neonates demonstrated LGA. Conclusions: Although participants reached the target HbA1c concentrations, mothers of LGA newborns had higher first-trimester HbA1c, as well as higher time above target range, higher mean glucose concentrations, and more glycemic fluctuations, suggesting that several CGM metrics associated with maternal hyperglycemia are associated with LGA in pregnancies with T1D.

Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus.

Preeclampsia (PE) is one of the leading causes of mortality and morbidity in pregnant women. Pregestational diabetes (PGDM) patients are prone to vascular complications and preeclampsia, whereas vascular exposure to hyperglycemia induces inflammation, vascular remodeling, and arterial stiffness. Corin is a serine protease, converting inactive pro-atrial natriuretic peptide (pro-ANP) into an active form. It also promotes salt and water excretion by activating atrial natriuretic peptide (ANP), and significantly increases trophoblast invasion. The study aimed to determine whether corin may be a predictor of PE in a high-risk group-women with long-term PGDM. The nested case-control prospective study involved 63 patients with long-term pregestational type 1 diabetes (PGDM). In total, 17 patients developed preeclampsia (the study group), whereas 43 patients without PE constituted the control group. To assess corin concentration, blood samples were collected at two time points: between 18th-22nd week of gestation and 28th-32nd week of gestation. PE patients presented significantly higher mid-gestation corin levels, urine protein loss in each trimester, serum creatinine in the third trimester, and lower creatinine clearance in the third trimester. The results of our study indicate that serum corin assessment may play a role in predicting preeclampsia. Thus, it may be included in the PE risk calculator, initially in high-risk groups, such as patients with PGDM.

Maternal serum proteomic profiles of pregnant women with type 1 diabetes.

Despite improvement in the care of diabetes over the years, pregnancy complicated by type 1 diabetes (T1DM) is still associated with adverse maternal and neonatal outcomes. To date, proteomics studies have been conducted to identify T1DM biomarkers in non-pregnant women, however, no studies included T1DM pregnant women. In this study serum proteomic profiling was conducted in pregnant women with T1DM in the late third trimester. Serum samples were collected from 40 women with T1DM and 38 healthy controls within 3 days before delivery at term pregnancy. Significant differences between serum proteomic patterns were revealed, showing discriminative peaks for complement C3 and C4-A, kininogen-1, and fibrinogen alpha chain. Quantification of selected discriminative proteins by ELISA kits was also performed. The serum concentration of kininogen-1 was significantly lower in women with T1DM than in controls. There were no significant differences in serum concentrations of complement C3 and complement C4-A between study groups. These data indicate that pregnant women with T1DM have a distinct proteomic profile involving proteins in the coagulation and inflammatory pathways. However, their utility as biomarkers of pregnancy complications in women with T1DM warrants further investigation.