Publications by authors named "Paweł Gutaj"

31 Publications

Fetal growth trajectory in type 1 pregestational diabetes (PGDM) - an ultrasound study.

Ginekol Pol 2021 ;92(2):110-117

Department of Reproduction, Chair of Obstertics, Gynecology and Gynecological Oncology, Poznan University of Medical Sciences, Poland, Poland.

Objectives: Growth disorders are frequent in diabetic pregnancies. However, they are difficult to predict and capture early during pregnancy. These newborns are at risk of obesity, diabetes, and cardiovascular disease. While developing, fetal growth abnormalities are typically progressive. Therefore, capturing the earliest moment when they emerge is essential to guide subsequent obstetric management.

Material And Methods: We aimed to analyze fetal ultrasound growth trajectories in type 1 diabetics. Moreover, we aimed to establish time points when first ultrasound manifestations of fetal growth abnormalities appear and to identify factors that affect fetal growth in women with diabetes. We collected clinical and ultrasound data from 200 patients with PGDM managed in the third-referential centre for diabetes in pregnancy. During every visit, patients underwent an ultrasound examination according to a standard protocol giving 1072 ultrasound scan's records. Every ultrasound consisted of fetal weight estimation, according to the Hadlock 3 formula. Retrospectively patients were divided into three groups depending on neonatal weight. In the group of 200 patients, 60 (30%) delivered LGA and 9 (4.5%) SGA newborns.

Results: Fetal growth trajectories show different patterns among fetuses with growth abnormalities in women with type 1 diabetes. The moment, when fetal growth curves diverge, seems to take place in the second trimester, just after the 23rd week of gestation.

Conclusions: It suggests that fetal growth abnormalities in type 1 diabetes may have its roots much earlier than expected. In the first trimester, there were differences in LDL-cholesterol, total cholesterol, triglyceride levels and in insulin requirements between AGA, SGA and LGA subgroups.
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http://dx.doi.org/10.5603/GP.a2020.0136DOI Listing
January 2021

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

Mol Med 2021 01 20;27(1). Epub 2021 Jan 20.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

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) 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) 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.
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http://dx.doi.org/10.1186/s10020-020-00266-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818927PMC
January 2021

Perinatal Outcomes in a Population of Diabetic and Obese Pregnant Women-The Results of the Polish National Survey.

Int J Environ Res Public Health 2021 01 11;18(2). Epub 2021 Jan 11.

World Institute for Family Health, Calisia University, 62-800 Kalisz, Poland.

Obesity and diabetes increase the risk of complications during gestation and at delivery. The aim of this study was to compare the perinatal outcomes in the populations of diabetic and obese Polish women, based on the results of a national survey performed in years 2012 and 2017, as well as to determine the risk factors of the gestational diabetes mellitus (GDM). Questionnaires from 6276 women were collected. Obese women constituted 5.5% and 7.5% of study population in years 2012 and 2017, respectively. Among women whose pregnancies were complicated by diabetes mellitus, GDM constituted the most common type of glucose intolerance during both time periods (2012: 89% vs. 2017: 85.6%). In the group of obese women an insignificant increase in the rate of induced deliveries was noted (2012: 9.9% vs. 2017: 11.7%), whereas the fetal birth-weight decreased significantly (2012: 3565 g vs. 2017: 3405 g, < 0.05). In the group of diabetic pregnant women the percentage of cesarean sections, labour inductions and fetal birth defects was characterized by an insignificant upward trend. Risk of GDM was significantly increased in women aged over 35 years-(2012: OR 1.9 (95% CI: 1.1-2.9) and 2017: OR = 2.1 (95% CI: 1.5-2.9), < 0.05-, as well as in overweight women-2012: OR 1.8 (95% CI: 1.2-2.7) and 2017: OR 2.6 (95% CI: 1.9-3.4), < 0.05-during both analysed time periods. Based on the study results, it is necessary to develop population-based programmes to prevent obesity and to introduce and enforce the rules of appropriate screening for glucose tolerance disorders during pregnancy.
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http://dx.doi.org/10.3390/ijerph18020560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827210PMC
January 2021

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

Int J Mol Sci 2020 Dec 10;21(24). Epub 2020 Dec 10.

Department of Reproduction, Chair of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 60-535 Poznan, Poland.

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.
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http://dx.doi.org/10.3390/ijms21249408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762997PMC
December 2020

Early Screening for Gestational Diabetes Using IADPSG Criteria May Be a Useful Predictor for Congenital Anomalies: Preliminary Data from a High-Risk Population.

J Clin Med 2020 Nov 4;9(11). Epub 2020 Nov 4.

Department of Reproduction, Poznan University of Medical Sciences, 60-512 Poznan, Poland.

Background: Our aim was to investigate whether the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) glycemic thresholds used for detecting hyperglycemia in pregnancy can be predictive for malformations in women with hyperglycemia detected in early pregnancy.

Methods: a single-center, retrospective observational trial of 125 mother-infant pairs from singleton pregnancies with hyperglycemia according to the IADPSG criteria diagnosed at the gestational age below 16 weeks. Glucose values obtained from 75-g OGTT (oral glucose tolerance test) were investigated as predictors for congenital malformations in newborns.

Results: Characteristics of the cohort: maternal age: 31.5 ± 5.2, pre-pregnancy body mass index (BMI) ≥ 30 kg/m: 42.0%, gestational age at diagnosis (weeks): 12.0 ± 4.0, and newborns with congenital malformations: 8.8%. Fasting blood glycemia (FBG) and HbA1c (Haemoglobin A1c) at baseline significantly predicted the outcome (expB: 1.06 (1.02-1.1), = 0.007 and expB: 2.05 (1.24-3.38), = 0.005, respectively). Both the fasting blood glucose (FBG) value of 5.1 mmol/dL (diagnostic for gestational diabetes mellitus (GDM)) and 5.5 mmol/dL (upper limit for normoglycemia in the general population) significantly increased the likelihood ratio (LR) for fetal malformations: 1.3 (1.1; 1.4) and 1.5 (1.0; 2.4), respectively.

Conclusions: (1) Fasting glycemia diagnostic for GDM measured in early pregnancy is associated with a significantly elevated risk for congenital malformations. (2) Our data suggest that women at elevated risks of GDM/diabetes in pregnancy (DiP) should have their fasting blood glucose assessed before becoming pregnant, and the optimization of glycemic control should be considered if the FBG exceeds 5.1 mmol/dL.
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http://dx.doi.org/10.3390/jcm9113553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694288PMC
November 2020

Pregnancy Outcomes in Women with Long-Duration Type 1 Diabetes-25 Years of Experience.

J Clin Med 2020 Oct 8;9(10). Epub 2020 Oct 8.

Department of Reproduction, Poznan University of Medical Sciences, Polna 33, 60-525 Poznań, Poland.

Aims: Our study aimed to examine the pregnancy outcomes (maternal and fetal) concerning different models of antenatal care across a period of over 25 years (1993-2018) in 459 women with type 1 diabetes. Data from patients with a history of the condition lasting at least 15 years were considered eligible for analysis.

Methods: The study group was divided into three cohorts based on the different models of treatment used in Poznan University Hospital, Poland: 1993-2000 (cohort I, = 91), 2001-2005 (cohort II, = 83), 2006-2018 (cohort III, = 284). To identify predictors for the selected dichotomous outcomes, we calculated the risks for fetal or maternal complications as dependent variables for cohorts II and III against cohort I, using multivariate logistic regression analysis.

Results: The mean gestational age was 36.8 ± 2.4 weeks in the total cohort. The percentages of deliveries before the 33rd and the 37th weeks was high. We observed a decreasing percentage during the following periods, from 41.5% in the first period to 30.4% in the third group. There was a tendency for newborn weight to show a gradual increase across three time periods (2850, 3189, 3321 g, < 0.0001). In the last period, we noticed significantly more newborns delivered after 36 weeks with a weight above 4000 g and below 2500 g. Caesarean section was performed in 88% of patients from the whole group, but in the subsequent periods this number visibly decreased (from 97.6%, 86.7%, to 71%, = 0.001). The number of emergency caesarean sections was lowest in the third period (27.5%, 16.7%, 11.2%, = 0.006). We observed a decreasing number of "small for gestational age" newborns (SGA) in consecutive periods of treatment (from 24.4% to 8.7%, = 0.002), but also a higher percentage of "large for gestational age" (LGA) newborns (from 6.1% to 21.6%, = 0.001). Modification of treatment might be associated with the gradual reduction of SGA rates (cohort I 3.6%, cohort III 2.3% < 0,0005).

Conclusions: Strict glycemic and blood pressure control from the very beginning of pregnancy, as well as modern fetal surveillance techniques, may contribute to the improvement of perinatal outcomes in women with long-duration type 1 diabetes.
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http://dx.doi.org/10.3390/jcm9103223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600991PMC
October 2020

Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

PLoS One 2020 8;15(10):e0237843. Epub 2020 Oct 8.

Department of Reproduction, Chair of Obstetrics, Gynaecology and Oncology, Poznan University of Medical Sciences, Poznan, Poland.

Ojectives: Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date.

Patients/methods: This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan).

Results: Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04).

Conclusions: Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237843PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544075PMC
November 2020

Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.

BMC Med Genomics 2020 07 7;13(1):97. Epub 2020 Jul 7.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment.

Methods: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor.

Results: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (β = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts.

Conclusions: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.
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http://dx.doi.org/10.1186/s12920-020-00752-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341625PMC
July 2020

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

J Clin Med 2020 Apr 16;9(4). Epub 2020 Apr 16.

Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 33 Polna St, 60-535 Poznan, Poland.

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 β-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.
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http://dx.doi.org/10.3390/jcm9041142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230810PMC
April 2020

Human Wharton's Jelly-Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials.

J Clin Med 2020 Apr 12;9(4). Epub 2020 Apr 12.

Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.

Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton's jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton's jelly, is a promising source of mesenchymal stem cells.
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http://dx.doi.org/10.3390/jcm9041102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230974PMC
April 2020

Determinants of adiponectin levels during pregnancy in women with type 1 diabetes mellitus.

Pol Arch Intern Med 2020 03 10;130(3):252-254. Epub 2020 Mar 10.

Department of Reproduction, Poznan University of Medical Sciences, Poznań, Poland

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http://dx.doi.org/10.20452/pamw.15227DOI Listing
March 2020

Maternal risk factors for neonatal acidosis in women with type 1 diabetes.

Pol Arch Intern Med 2019 05 25;129(5):316-320. Epub 2019 Apr 25.

Division of Reproduction, Poznan University of Medical Sciences, Poznań, Poland

INTRODUCTION Type 1 diabetes in the mother is associated with high risk of adverse neonatal outcomes. OBJECTIVES The aim of this study was to identify maternal factors associated with low arterial pH values (pH <7.10) in infants of mothers with type 1 diabetes. PATIENTS AND METHODS Data from 789 women were included in the analysis. Based on pH values in the umbilical arteries of infants, women were divided into 2 groups: those with normal pH, defined as pH of 7.1 or higher, and those with low pH, defined as pH lower than 7.1. A logistic regression analysis was used to identify the determinants of low pH in the umbilical artery, with data presented as odds ratios and 95% CIs. RESULTS Low umbilical artery pH was observed in 72 infants (9.1%). There was an association between maternal glycated hemoglobin A1c (HbA1c) levels measured before delivery and low umbilical artery pH (odds ratio [OR] 1.40; 95% CI, 1.11-1.78; P = 0.01). A similar association was found for HbA1c levels measured between 20 and 24 weeks' gestation (OR 1.29; 95% CI, 1.03-1.63; P = 0.03). There was no association between the levels of HbA1c in the first trimester or lack of preconception care and low umbilical artery pH. In logistic regression, urgent cesarean section was associated with low umbilical artery pH (OR, 1.64; 95% CI, 1.11-2.44; P = 0.01), and this association was independent of HbA1c levels measured before delivery. CONCLUSIONS Lack of sufficient glycemic control in pregnancy is the strongest predictor of neonatal acidosis in women with type 1 diabetes.
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http://dx.doi.org/10.20452/pamw.14809DOI Listing
May 2019

Continuous subcutaneous insulin infusion reduces neonatal risk in pregnant women with type 1 diabetes mellitus.

Ginekol Pol 2019 ;90(3):154-160

Department of Reproduction, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: An attempt was made to demonstrate the superiority of the treatment model using continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) of insulin in achieving a successful pregnancy outcome and good newborn's condition in patients with type 1 diabetes.

Material And Methods: The study included 297 infants born to type 1 diabetic patients; 175 patients were treated with MDI and 122 with CSII. Maternal metabolic control during pregnancy, gestational weight gain, insulin requirements, pregnancy outcome and neonatal status were compared between MDI and CSII arm. The composite adverse neonatal outcome was diagnosed if at least one of the following was found: abnormal birth weight (LGA or SGA), congenital malformation, miscarriage, intrauterine fetal death, emergency CS due to fetal risk, iatrogenic prematurity, RDS, hypoglycemia, hyperbilirubinemia, and the postpartum pH in the umbilical artery ≤ 7.1.

Results: The studied groups did not differ regarding gestational week at delivery, a proportion of births at full term, preterm births, miscarriages, or late pregnancy losses (intrauterine fetal death > 22 weeks). Newborns of mothers treated with CSII showed lower incidence of neonatal complications (composite adverse neonatal outcome) compared to those of mothers treated with MDI (60% vs 74%, respectively; p = 0.01). We did not find any association between the mode of treatment and composite adverse maternal outcome.

Conclusions: The use of CSII in the treatment of pregnant women with type 1 diabetes was associated with reduced number of neonatal complications presented as neonatal composite outcome but had no influence on maternal outcome.
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http://dx.doi.org/10.5603/GP.2019.0028DOI Listing
February 2020

Determinants of preeclampsia in women with type 1 diabetes.

Acta Diabetol 2017 Dec 3;54(12):1115-1121. Epub 2017 Oct 3.

Division of Reproduction, Department of Obstetrics, Gynecology and Gynecological Oncology, Poznan University of Medical Sciences, 33 Polna St, 60-535, Poznań, Poland.

Aims: Despite improvement in diabetic care over the years, the incidence of hypertensive disorders of pregnancy is still very high. Therefore, the aim of our study was to determine risk factors for PE in women with T1DM.

Methods: This study was a prospective, nested case-control study on a population of 165 women with T1DM. Women were divided into 3 subgroups: normotensive (N = 141), gestational hypertension (GH) (N = 8), and PE (N = 16). Clinical data were collected in the first trimester (< 12th week), in mid-pregnancy (20-24th weeks), and just prior to delivery (34-39th weeks). IR in the first trimester was quantified using the estimated glucose disposal rate formula (eGDR, milligrams/kilogram/minute). Simple logistic regression was used to search for factors associated with PE and GH. For multivariate comparisons, we used multiple logistic regression with stepwise selection.

Results: All preeclampsia cases were diagnosed in primiparae. The presence of vasculopathy was the strongest determinant of PE (OR 10.8, 95% CI 3.27-35.97, P = 0.0001), followed by a history of chronic hypertension (6.05, 1.75-20.8, P = 0.004) and the duration of diabetes (1.11, 1.03-1.12, P = 0.009). However, chronic hypertension and duration of diabetes were no longer associated with PE after adjustment for the presence of vasculopathy. Higher gestational weight gain (GWG) was associated with PE, and this association remained significant after adjustment for first trimester body mass index (1.14, 1.02-1.28, P = 0.02). Both systolic and diastolic blood pressure assessed in the first trimester were significant determinants of PE; however, this association was no longer observed after adjustment for the presence of chronic hypertension. Glycated hemoglobin (HbA) levels from all 3 trimesters were significantly associated with PE (first trimester: 1.38, 1.01-1.87, P = 0.04; second trimester: 2.76, 1.43-5.31, P = 0.002; third trimester: 2.42, 1.30-4.51, P = 0.005). There was a negative association between eGDR and PE (0.66, 0.50-0.87, P = 0.003). Among lipids, triglycerides (TG) in all 3 trimesters were positively associated with PE, and this association was independent of HbA levels (first trimester: 5.32, 1.65-17.18, P = 0.005; second trimester: 2.52, 1.02-6.26, P = 0.05; third trimester: 2.28, 1.39-3.74, P = 0.001. We did not find any predictors of GH in the regression analysis among all analyzed factors.

Conclusions: Primiparity and diabetic vasculopathy seem to be the strongest risk factors for PE in women with type 1 diabetes. However, preexisting hypertension and higher GWG were also associated with PE in women with T1DM. Among laboratory results, higher HbA and TG levels in all 3 trimesters were associated with PE. The association between higher IR and PE in women with T1DM needs further study.
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http://dx.doi.org/10.1007/s00592-017-1053-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680366PMC
December 2017

Maternal lipids associated with large-for-gestational-age birth weight in women with type 1 diabetes: results from a prospective single-center study.

Arch Med Sci 2017 Jun 16;13(4):753-759. Epub 2016 Mar 16.

Department of Obstetrics and Women's Diseases, Poznan University of Medical Sciences, Poznan, Poland.

Introduction: Despite improvement in diabetes care over the years, the incidence of macrosomia in type 1 diabetic mothers is still very high and even shows an increasing tendency. It is suggested that other factors that maternal hyperglycemia might be associated with excessive fetal growth in diabetic mothers. The aim of this study was to determine whether maternal lipids might contribute to high rates of large-for-gestational-age (LGA) newborns in women with type 1 diabetes (T1DM).

Material And Methods: This prospective, single-center study was performed in a population of women with T1DM admitted to the perinatal center for women with diabetes. Data were collected in the first trimester (< 12 week), in mid-pregnancy (20-24 weeks), and before delivery (34-39 weeks).

Results: Among 114 women included in the analysis, 30 (26.3%) delivered LGA newborns. The remaining 84 (73.7%) newborns were appropriate for gestational age (AGA). Lower high-density lipoprotein (HDL) HDL concentration in the first trimester was significantly associated with LGA ( = 0.01). Similar associations were observed for the HDL concentrations in mid-pregnancy ( = 0.04) and before delivery ( = 0.03). Higher triglyceride concentrations in the first trimester ( = 0.02) and before delivery ( = 0.008) were associated with LGA. Higher glycated haemoglobin (HbA) levels in mid-pregnancy and before delivery were associated with LGA. The associations between maternal lipids and LGA were independent of maternal body mass index at onset of the study, gestational weight gain and HbA concentrations.

Conclusions: Decreased HDL and increased triglycerides during pregnancy might contribute to the development of LGA in women with type 1 diabetes.
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http://dx.doi.org/10.5114/aoms.2016.58619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510499PMC
June 2017

Determinants of C-reactive protein concentrations in pregnant women with type 1 diabetes.

Pol Arch Med Wewn 2016 Apr 13;126(4):230-6. Epub 2016 Apr 13.

INTRODUCTION    Increased C-reactive protein (CRP) concentrations during pregnancy are associated with several perinatal complications. OBJECTIVES    The aim of the study was to assess serum CRP concentrations and identify its determinants in pregnant women with type 1 diabetes. PATIENTS AND METHODS    CRP concentrations were determined using a high-sensitivity assay (hs-CRP) in the first trimester (I, week <12 of gestation), in mid-pregnancy (II, weeks 20 to 24 of gestation), and in the late third trimester (III, weeks 34 to 39 of gestation) in a group of 73 patients with type 1 diabetes. RESULTS    There was a significant increase in CRP concentrations between the first trimester and mid‑pregnancy (median [interquartile range], 2.5 mg/l [1.3-4.5 mg/l] and 5.6 mg/l [2.5-11.6 mg/l]; P = 0.0001), which then stabilized with no further change between mid-pregnancy and the late third trimester (5.7 mg/l [2.5-9.6 mg/l]). CRP concentrations in all 3 trimesters were positively correlated with the waist‑to-hip ratio (I, P <0.0001; II, P = 0.0004; III, P = 0.0369) and body mass index (I, P = 0.015; II, P = 0.0025; III, P = 0.0048), measured in the first trimester. CRP concentrations during pregnancy were positively correlated with a measure of insulin resistance, namely, the estimated glucose disposal rate, assessed in the first trimester (I, P = 0.01; II, P = 0.0165; III, P = 0.0062). There was a positive correlation between the levels of hs-CRP and total cholesterol (P = 0.001), low-density lipoprotein cholesterol (P = 0.013), and triglycerides (P = 0.0014) in the first trimester. There was no significant correlation between CRP and hemoglobin A1c, daily insulin requirement/kg, high-density lipoprotein cholesterol levels, maternal age, and diabetes duration. CONCLUSIONS    Adiposity, abnormal body fat distribution, and insulin resistance are the major determinants of CRP concentrations in pregnant women with type 1 diabetes. Our results confirm the importance of weight control before pregnancy in women with type 1 diabetes.
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http://dx.doi.org/10.20452/pamw.3370DOI Listing
April 2016

The appearance of newly identified intraocular lesions in Gaucher disease type 3 despite long-term glucocerebrosidase replacement therapy.

Ups J Med Sci 2016 Aug 11;121(3):192-5. Epub 2016 Apr 11.

a Department of Endocrinology, Metabolism and Internal Medicine , Poznan University of Medical Sciences , Poznan , Poland ;

Background Gaucher disease (GD) is an autosomal recessive lipid storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase. The presence of central nervous system disease is a hallmark of the neuronopathic forms of GD (types 2 and 3). Intraocular lesions (e.g. corneal clouding, retinal lesions, and vitreous opacities) have been infrequently reported in GD type 3 (GD3). Moreover, there are virtually no published data on the occurrence and natural course of intraocular lesions in GD3 patients treated with enzyme replacement therapy (ERT). Case presentation We describe the case of a 26-year-old Polish male with L444P homozygous GD3 (mutation c.1448T > C in the GBA1 gene) who developed fundus lesions despite 10 years of ERT. At the age of 23 years, a spectral domain optical coherence tomography (OCT) examination was performed which disclosed the presence of discrete lesions located preretinally, intraretinally in the nerve fiber layer, and in the vitreous body. A 3-year follow-up OCT examination has not shown any significant progression of the fundus lesions. Conclusions To the best of our knowledge, this is the first published report describing the occurrence of newly identified retinal and preretinal lesions occurring during long-term ERT in GD3. We recommend that a careful ophthalmic assessment, including a dilated fundus examination, should be included as part of annual follow-up in patients with GD3. Further studies are needed to understand the nature and clinical course of these changes and whether or not these intraocular findings have any predictive value in the context of neurologic and skeletal progression in GD3.
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http://dx.doi.org/10.3109/03009734.2016.1158756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967266PMC
August 2016

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

Curr Diab Rep 2016 May;16(5):39

Department of Obstetrics and Women's Diseases, Poznan University of Medical Sciences, Polna 33, 60-535, Poznan, Poland.

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.
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http://dx.doi.org/10.1007/s11892-016-0732-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794518PMC
May 2016

ThyPROpl--The Polish version of the thyroid-specific quality of life questionnaire ThyPRO.

Endokrynol Pol 2015 ;66(4):367-80

Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poland.

Introduction: Thyroid disorders have a significant impact on patients' quality of life. ThyPRO is a thyroid-specific quality of life (QoL) questionnaire applicable to patients with benign thyroid disorders. There is substantial evidence for its clinical validity and reliability in patients with benign thyroid disorders. Our aim was to develop a validated Polish version of this questionnaire (ThyPROpl).

Material And Methods: ThyPROpl was translated and validated according to standard methodology for translation of patient-reported outcomes (PRO). Firstly, two independent translations from English to Polish were performed by two translators native in Polish, and a consensus version was reached in collaboration with an in-country consultant. A third translator prepared a back-translation from Polish to English, which likewise was reviewed by the in-country consultant. The backwards translation was reviewed by a PRO translation expert native in English (Health Research Associates HRA) and by the developer of ThyPRO, who provided additional revisions. Finally, ThyPROpl was tested among five patients with thyroid disorders with cognitive interview techniques, and new changes and clarifications needed for its full understanding were made.

Results: ThyPROpl is a linguistically validated version of the original ThyPRO questionnaire.

Conclusions: We recommend ThyPROpl for the evaluation of QoL among Polish patients with benign thyroid disorders. ThyPRO has now been translated into 13 languages.
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http://dx.doi.org/10.5603/EP.2015.0047DOI Listing
February 2017

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

Ginekol Pol 2015 Mar;86(3):219-23

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
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http://dx.doi.org/10.17772/gp/2065DOI Listing
March 2015

Association between preconceptional treatment with insulin pumps and improved metabolic status in early pregnancy in women with type 1 diabetes.

Pol Arch Med Wewn 2015 1;125(5):329-36. Epub 2015 Apr 1.

Introduction: An adverse intrauterine environment in early pregnancy in women with type 1 diabetes is associated with several perinatal complications including spontaneous abortions, fetal congenital defects, and preeclampsia.

Objectives: We compared metabolic parameters in the first trimester of pregnancy between women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) and those treated with multiple daily injections (MDI).

Patients And Methods: A total of 168 women in the first trimester of pregnancy (33 using CSII and 135 using MDI) were enrolled in this cross-sectional single-center study. Anthropometric parameters, fasting serum levels of hemoglobin A(1c) (HbA(1c)), lipid profile, and estimated glucose disposal rate (eGDR) were determined.

Results: Patients did not differ in gestational or maternal age, diabetes duration, and the frequency of planned pregnancies. Women using CSII before pregnancy had lower body mass index and waist-to-hip ratio than those using MDI (22.3 vs 23.3 and 0.77 vs 0.79, respectively, P = 0.01). A similar number of women had hypertension; however, the CSII group had lower diastolic blood pressure (P = 0.02). Moreover, the CSII group had a significantly lower insulin requirement (0.54 vs 0.63 units/kg; P = 0.02), significantly higher eGDR (11.3 vs 10.5 mg/kg/min; P = 0.0007), and significantly lower serum triglyceride levels (53.1 vs 61.8 mg/dl; P = 0.004). In a multiple regression analysis, CSII therapy was associated with higher eGDR, lower HbA(1c), and lower serum triglyceride levels.

Conclusions: The use of CSII before pregnancy in patients with type 1 diabetes is associated with better metabolic profile in the first trimester.
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http://dx.doi.org/10.20452/pamw.2830DOI Listing
January 2017

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

Gynecol Endocrinol 2015 Feb 30;31(2):116-8. Epub 2014 Sep 30.

Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences , Poznan , Poland and.

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.
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http://dx.doi.org/10.3109/09513590.2014.964200DOI Listing
February 2015

Influence of cigarette smoking on thyroid gland--an update.

Endokrynol Pol 2014 ;65(1):54-62

Many studies have shown that cigarette smoking exerts multiple effects on the thyroid gland. Smoking seems to induce changes in thyroid function tests, like decrease in TSH and increase in thyroid hormones. However, these alterations are usually mild. In addition, tobacco smoking may also play a role in thyroid autoimmunity. Many studies have confirmed a significant influence of smoking on Graves' hyperthyroidism and particularly on Graves' orbitopathy. Here, smoking may increase the risk of disease development, may reduce the effectiveness of treatment, and eventually induce relapse. The role of smoking in Hashimoto's thyroiditis is not as well established as in Graves' disease. Nonetheless, lower prevalence of thyroglobulin antibodies, thyroperoxidase antibodies and hypothyroidism were found in smokers. These findings contrast with a study that reported increased risk of hypothyroidism in smokers with Hashimoto's thyroiditis. Moreover, cigarette smoking increases the incidence of multinodular goitre, especially in iodine-deficient areas. Some studies have examined cigarette smoking in relation to the risk of thyroid cancer. Interestingly, many of them have shown that smoking may reduce the risk of differentiated thyroid cancer. Furthermore, both active and passive smoking during pregnancy might modify maternal and foetal thyroid function. This review evaluates the current data concerning the influence of cigarette smoking on thyroid gland, including hormonal changes, autoimmunity and selected diseases. These findings, however, in our opinion, should be carefully evaluated and some of them are not totally evidence-based. Further studies are required to explain the effects of smoking upon thyroid pathophysiology.
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http://dx.doi.org/10.5603/EP.2014.0008DOI Listing
October 2015

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

J Perinat Med 2014 Sep;42(5):629-33

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.
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http://dx.doi.org/10.1515/jpm-2013-0227DOI Listing
September 2014

Recommendations of the Polish Society of Endocrinology and Polish Diabetes Association for the management of thyroid dysfunction in type 1 and type 2 diabetes.

Endokrynol Pol 2013 ;64(1):73-7

Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewskiego St. 49, Poznan, Poland.

Thyroid disorders are more frequently observed in diabetic patients. These conditions have been shown to be mainly of autoimmune origin and all of them may lead to hormonal imbalance. Especially strong links exist between autoimmune thyroid diseases (AITD) and type 1 diabetes. Importantly, both hypothyroidism and hyperthyroidism can adversely affect metabolic control of diabetes. These recommendations propose diagnostic and therapeutic algorithms for thyroid dysfunction in diabetic patients.
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May 2013

Maternal factors predictive of first‑trimester pregnancy loss in women with pregestational diabetes.

Pol Arch Med Wewn 2013 10;123(1-2):21-8. Epub 2013 Jan 10.

Department of Obstetrics and Women’s Diseases, Poznan University of Medical Sciences, Poznań, Poland.

Introduction: Diabetes is one of the most frequent chronic diseases in women of childbearing age, which significantly increases the risk of complications at every stage of pregnancy.

Objectives: The aim of the study was to investigate any maternal factors that may be associated with the risk of first‑trimester pregnancy loss in patients with pregestational diabetes.

Patients And Methods: It was a retrospective study based on the data of 91 diabetic women in singleton pregnancy and with good perinatal outcome (74 women [81.3%] with type 1 and 17 [18.7%] with type 2 diabetes), and 60 diabetic women with a miscarriage (48 women [80%] with type 1 and 12 [20%] with type 2 diabetes). We analyzed selected maternal parameters at the first admission to the obstetrics department.

Results: Women in the miscarriage group were older compared with those in the good outcome group (29.5 ±5.4 years vs. 26.4 ±5.3 years; P <0.001). Hemoglobin A1c (HbA1c) was higher in the miscarriage group compared with the good outcome group (8.2% ±1.9% vs. 7.2% ±1.8%; P <0.001). In a stepwise logistic regression analysis, maternal age at booking and HbA1c were found to be significant predictors of miscarriage (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18 and OR, 1.28; 95% CI, 1.026-1.61; respectively). A statistically insignificant trend towards first-trimester pregnancy loss was observed in patients with hypertension, overweight/obesity, unplanned pregnancy, longer duration of diabetes, and diabetic vascular complications.

Conclusions: Suboptimal metabolic control and increasing maternal age are the most significant risk factors for first‑trimester miscarriage in women with pregestational diabetes.
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http://dx.doi.org/10.20452/pamw.1585DOI Listing
January 2014

[Maternal body mass index and gestational weight gain and their association with perinatal outcome in women with gestational diabetes].

Ginekol Pol 2011 Nov;82(11):827-33

Klinika Połoznictwa i Chorób Kobiecych, Katedra Ginekologii, Poloinictwa i Onkologii Ginekologicznej, Uniwersytet Medyczny im. K. Marcinkowskiego, Poznań, Polska.

Objectives: Maternal overweight and obesity constitute the most important factors causing perinatal complications. The purpose of the study was to analyze obstetrical results in overweight/obese pregnant women with gestational diabetes in relation to Institute of Health recommendations concerning gestational weight gain and assessment of the role of prepregnancy BMI in prediction of macrosomia, pregnancy induced hypertension and cesarean deliveries.

Material And Methods: Retrospective analysis of 209 overweight and obese pregnant women with gestational diabetes divided into 4 subgroups according to The National Institute of Health (USA) recommendations. The following data were included in the analysis: gestational week in which GDM was diagnosed; HbA1c level in the first and third trimester just before delivery; incidence of pregnancy induced hypertension; incidence of cesarean deliveries; incidence of macrosomia. The following data of II, III, IV subgroups were compared to these found in I subgroup which was classified as the control group. Selected obstetric parameters were also compared between subgroups II, III, IV RESULTS: The selected parameters of subgroups II, III, IV were not significantly different from these of subgroup I. Pregnancy induced hypertension was diagnosed more frequently among subgroup II in comparison to subgroup III. Using ROC curves analysis, the role of pre-pregnancy BMI was found in the prognosis of: birth weight greater than 4300 g, pregnancy induced hypertension, cesarean delivery

Conclusions: 1. The application of the National Institute of Health recommendations on gestational weight gain is limited in case of overweight or obese pregnant women with gestational diabetes mellitus. 2. Excessive weight gain during pregnancy according to National Health Institute recommendations may increase the risk of developing pregnancy induced hypertension in comparison to a pregnant women with weight gain less than recommended, but greater than zero. 3. Increased prepregnancy BMI has a role in prediction of birth weight greater than 4300 g, pregnancy induced hypertension, cesarean delivery
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November 2011