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.

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.

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.

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.

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.

Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials.

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

Endothelial Dysfunction in Pregnancy Complications.

The endothelium, which constitutes the inner layer of blood vessels and lymphatic structures, plays an important role in various physiological functions. Alterations in structure, integrity and function of the endothelial layer during pregnancy have been associated with numerous gestational complications, including clinically significant disorders, such as preeclampsia, fetal growth restriction, and diabetes. While numerous experimental studies have focused on establishing the role of endothelial dysfunction in pathophysiology of these gestational complications, their mechanisms remain unknown. Numerous biomarkers of endothelial dysfunction have been proposed, together with the mechanisms by which they relate to individual gestational complications. However, more studies are required to determine clinically relevant markers specific to a gestational complication of interest, as currently most of them present a significant overlap. Although the independent diagnostic value of such markers remains to be insufficient for implementation in standard clinical practice at the moment, inclusion of certain markers in predictive multifactorial models can improve their prognostic value. The future of the research in this field lies in the fine tuning of the clinical markers to be used, as well as identifying possible therapeutic techniques to prevent or reverse endothelial damage.

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.

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications.

Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

Biomarkers in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

PURPOSE: The aim of the presented study was to evaluate the differences between selected biochemical markers in infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) and their impact on patient prognosis. METHODS: A total of 57 cooled newborns were divided into groups according to Sarnat staging of HIE (A, moderate vs. B, severe). The differences between groups were evaluated depending on the mode of delivery, pregnancy and labor complications, gestational age at birth, birth weight, and Apgar score at 1.3 and 5 min. The differences in biochemical biomarkers of HIE (pH, base excess, serum lactate) as well as biomarkers of hepatic injury (aspartate transaminase, (AST), alanine transaminase (ALT), prothrombin time (PT), and activated partial thromboplastin time (APTT)), kidney failure (creatinine, urea), myocardial injury (troponin T (TnT)), levels of fibrinogen, and platelet counts were also examined. Univariate Kaplan-Meier method was used for survival analyses. RESULTS: The biomarker levels in severe HIE newborns compared with moderate were as follows: pH (7.10 vs. 6.99), serum lactate (22.50 vs. 17.00 mg/dL), AST (109.50 vs. 270.55 IU/L), ALT (27.30 vs. 108.05 IU/L), PT (17.00 vs. 44.20 s), APTT (47.75 vs. 47.90 s), TnT (0.22 vs. 0.85 ng/mL), creatinine (0.68 vs. 1.15 mg/dL), urea (44.55 vs. 73.30 mg/dL), and fibrinogen (1.65 vs. 1.90 mg/dL). Survival analyses showed significantly reduced survival for severe HIE infants (75%) vs. moderate HIE (100%). CONCLUSION: In conclusion, the severity of HIE can be evaluated based on selected markers; however, their levels do not correspond with future prognosis of newborns.

Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives.

Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic ß-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.

Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes.

Exosomes are a heterogenous subpopulation of extracellular vesicles 30-150 nm in range and of endosome-derived origin. We explored the exosome formation through different systems, including the endosomal sorting complex required for transport (ESCRT) and ESCRT-independent system, looking at the mechanisms of release. Different isolation techniques and specificities of exosomes from different tissues and cells are also discussed. Despite more than 30 years of research that followed their definition and indicated their important role in cellular physiology, the exosome biology is still in its infancy with rapidly growing interest. The reasons for the rapid increase in interest with respect to exosome biology is because they provide means of intercellular communication and transmission of macromolecules between cells, with a potential role in the development of diseases. Moreover, they have been investigated as prognostic biomarkers, with a potential for further development as diagnostic tools for neurodegenerative diseases and cancer. The interest grows further with the fact that exosomes were reported as useful vectors for drugs.

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials.

The deterioration of the human skeleton's capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.