Zbigniew Celewicz

Pregravid body mass index as a predictor of gestational diabetes mellitus.

Aims  It has been well documented that overweight or obesity before pregnancy is a strong predictor of gestational diabetes mellitus (GDM). The aim of this study was to assess the risk of GDM in women who were classified on the basis of pregravid body mass index (BMI) as normal weight and underweight.

Factors influencing risk of macrosomia in women with gestational diabetes mellitus undergoing intensive diabetic care

AIMS The aim of study was to assess the impact of intensive diabetic care, defined as target values for fasting glucose of 60-90mg/dl and 1-h postprandial glucose of below 130mg/dl, on neonatal birth weight in relation to risk indicators for fetal macrosomia in women with gestational diabetes mellitus (GDM). METHODS In women with (N=543) and without GDM (N=1011) age, height, weight, previous GDM, history of macrosomia, family history of type 2 diabetes, parity and weight gain during pregnancy were recorded. RESULTS Neonatal birth weight and frequency distribution of macrosomia and infants with small for gestational age did not differ between women with and without GDM. Neonatal birth weight was strongly associated with traditional risk predictors for GDM, such like prior macrosomia (OR 5.03; 95%CI 3.36-7.53), prior GDM (OR 2.52; 95%CI 1.37-4.64) and prepregnancy body mass index (BMI)>23kg/m(2) (OR 1.82; 95%CI 1.27-2.63). CONCLUSIONS Neonatal birth weight and the incidence of macrosomia were similar in comparison of pregnancies with and without GDM. In the population of Caucasian women the strongest single predictors for macrosomia were prior macrosomia, BMI>23kg/m(2) and prior GDM.

The influence of 3,3′,5-triiodo-l-thyronine on human haematopoiesis

Abstract.  Objectives: Thyroid hormones mediate many physiological and developmental functions in humans. The role of the 3,3′,5‐triiodo‐l‐thyronine (T3) in normal human haematopoiesis at the cellular and molecular levels has not been determined. In this study, it was revealed that the human haematopoietic system might be directly depended on T3 influence. Materials and methods: We detected the TRα1 and TRβ1 gene expression at the mRNA level in human cord blood, peripheral blood and bone marrow CD34+‐enriched progenitor cells, using the RT‐PCR method. Furthermore, we performed Western blotting to prove TRα1 and TRβ1 expression occurs at the protein level in human cord blood, peripheral blood and bone marrow CD34+ cells. In addition, the examined populations of cells were exposed in serum‐free conditions to increasing doses of T3 and were subsequently investigated for clonogenic growth of granulocyte‐macrophage colony‐forming unit and erythrocyte burst‐forming unit in methylcellulose cultures, and for the level of apoptosis, by employing annexin V staining and the terminal deoxynucleotidyltransferase‐mediated dUTP nick‐end labelling method. We investigated expression levels of apoptosis‐related Bax and antiapoptotic Bcl‐2 and Bcl‐xL genes in the examined cells. Results: We found that exposure to higher and lower than normal concentration of thyroid hormone significantly influenced clonogenecity and induced apoptosis in human haematopoietic progenitor cells. Conclusions: This study expands the understanding of the role of thyroid disorders in normal human haematopoiesis and indicates a direct influence of T3 on this process.

Low predictive value of traditional risk factors in identifying women at risk for gestational diabetes

Background. There is no worldwide agreement on the best way to screen for gestational diabetes mellitus (GDM), and different diagnostic methods have been developed in order to identify women at risk. The aim of this study was to evaluate the prevalence and predictive value of the traditional risk indicators for GDM in a large group of Caucasian women. Methods. We evaluated the frequency distribution of age, body mass index (BMI), prior macrosomia, prior GDM, and family history of diabetes of 1,414 pregnant women with GDM and 1,011 healthy pregnant women. Results. The distribution of risk factors in both groups was different and significantly higher in GDM women. The cut‐off value for age was 28years, and 23kg/m2 for BMI. The accumulation of two or more risk factors was frequent in GDM, but not in healthy women. By multiple logistic regression, there were significant interactions between independent variables of interest and GDM (OR: 3.19; p<0.001; sensitivity: 57.9%, specificity: 69.8%). The strongest predictors were prior GDM (OR: 4.35; 95% CI: 2.42–7.82) and a family history of diabetes (OR: 3.03; 95% CI: 2.47–3.72); less predictive were age (OR: 1.69; 95% CI: 1.44–1.99), BMI (OR: 1.50; 95% CI: 1.28–1.77), and prior macrosomia (OR: 1.64; 95% CI: 1.19–2.26). Conclusions. Selective screening based on traditional risk factors for GDM had relatively low sensitivity, and identified <60% of Caucasian women at risk. The cut‐off value for BMI as a risk indicator (23kg/m2) was lower than that proposed by guidelines about screening for GDM.

Birth weight predicts the risk of gestational diabetes mellitus and pregravid obesity

OBJECTIVES It has been suggested that birth weight may determine metabolic abnormalities later in life. The aim of the current study was to assess the association between birth weight and future risk of gestational diabetes mellitus (GDM) and pregravid obesity in a homogenous sample of Caucasian Polish women. METHODS In this retrospective study, we collected the medical reports of 787 women with GDM and 801 healthy pregnant women. We analyzed the following data: birth weight, age, pregravid weight, prior GDM, prior macrosomia, parity, and family history of diabetes. RESULTS Birth weight was inversely associated with the risk of GDM; for each decrease in birth weight of 500 g, the risk increased by 11% (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02-1.21). Birth weight was a strong predictor of GDM independent of other risk factors (OR, 1.19; 95% CI, 1.09-1.31), and it was positively correlated with pregravid weight (R = 0.21; P < 0.00001). An increase in birth weight of 500 g substantially increased the risk of overweight and obesity (OR, 1.17; 95% CI, 1.01-1.34 and OR, 1.35; 95% CI 1.11-1.64, respectively). Each of the traditional risk factors for GDM were also strong predictors of pregravid obesity: age (P < 0.0001), prior GDM (P < 0.01), prior macrosomia (P < 0.0001), multiparity (P < 0.0001), and maternal (but not paternal) history of diabetes (P < 0.0001). CONCLUSIONS Among Caucasian Polish women, the risk of GDM is associated with low birth weight, and pregravid obesity is associated with high birth weight. Traditional risk factors for GDM, including maternal (but not paternal) history of diabetes, are also risk factors for pregravid obesity.

Humoral Activity of Cord Blood-Derived Stem/Progenitor Cells: Implications for Stem Cell-Based Adjuvant Therapy of Neurodegenerative Disorders

Background Stem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34+, and CD133+ cells, with that in unsorted, nucleated cells (NCs). Methods and Results The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34+, and CD133+ cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34+, and CD133+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34+ or CD133+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. Conclusions Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

Circulating endothelial progenitor cells in premature infants: is there an association with premature birth complications?

Abstract Background: The most common morbidities in preterm infants are associated with vascular pathology. Endothelial progenitor cells (EPCs) have been implicated in repair of the vasculature, but their role in the pathogenesis of prematurity complications is not clear. Objectives: We prospectively investigated an association between the number of EPCs circulating in blood during delivery as well as 2 and 6 weeks afterwards, the level of growth factors regulating their migration/homing, and the incidence of premature birth complications. Patients and methods: The study groups consisted of 90 preterm and 52 full-term infants. Early-EPCs (CD133+CD34+CD144+) and late-EPCs (CD133–CD34+CD144+) were analysed in cord blood (CB) and peripheral blood (PB). Results: We found higher early- and late-EPC counts in the CB of premature infants compared with full-term babies. The number of circulating early- and late-EPCs was inversely associated with the Apgar score of preterm infants. A positive association between the early-EPC count and the risk of respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, and infections was found. Nevertheless, multivariate analysis revealed that a higher number of EPCs was not an independent predictor of prematurity complications, which were directly related to lower gestational age. The EPC count in full-term infants maintained a constant, relatively low level over the 6-week follow-up, whereas the EPC population in preterm infants gradually decreased during this period. Furthermore, the number of CB late-EPCs in preterm infants positively correlated with VEGF concentration. Conclusions: EPCs may play a considerable role in vascular development in preterm infants.

Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

BackgroundThe frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity.MethodsThe study groups consisted of 90 preterm (23–36 weeks of gestational age) and 52 full-term (37–41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (β-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables.ResultsWe found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p < 0.0001) and extensively decreases in preterm babies during next six weeks after birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of premature neonates is higher than those obtained from CB of full-term infants and strongly correlates with the number of CB-derived CSPCs.ConclusionWe conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.

The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene SUR1 (ABCC8) in Patients with Gestational Diabetes and Subsequent Glucose Metabolism Abnormalities

Aim. The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism, β-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM). Material and Methods. Study group included 199 women, diagnosed GDM within the last 5–12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined. Results. The distribution of the studied polymorphism in the two groups did not differ from each other (χ 2 = 0.34, P = 0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ 2 = 7,13, P = 0, 3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR. Conclusions. The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population.

Maternal Endothelin-1 and Cyclic Guanosine Monophosphate Concentrations in Pregnancies Complicated by Pregravid and Gestational Diabetes Mellitus

Background/Aims: Pregnancy complicated by diabetes is associated with increased risk of unfavorable obstetric outcomes. A common abnormality in diabetes is endothelial dysfunction resulting in an altered pattern of vasoactive substance production by the endothelial cells. The aim of study was to assess serum endothelin-1 (ET-1) and cyclic guanosine monophosphate (cGMP) in pregnant women with pregravid (PGDM) or gestational diabetes (GDM). Methods: At the time of delivery, serum ET-1, cGMP, glycated hemoglobin (A1c), fructosamine and non-fasting glucose were measured in 19 PGDM, 23 GDM and 18 controls. Results: ET-1 and cGMP were similar in all groups. In GDM there was a positive association between A1c and ET-1 (r = 0.437; p < 0.05) and cGMP (r = 0.542; p < 0.02). In the controls, but not in PGDM and GDM, we found a positive correlation between ET-1 and cGMP (r = 0.634; p < 0.005). In women with diabetes, an optimal (A1c <6%) or inadequate (A1c >6%) metabolic control of diabetes did not influence ET-1 or cGMP levels. Conclusions: In women with PGDM and GDM, serum ET-1 and cGMP were similar to the levels observed in healthy pregnant women. However, the physiological balance between vasoconstrictor and vasodilator substances might be defective in pregnancies complicated by diabetes.