Paweł Gutaj

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

Abstract 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.

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

Abstract 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.

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

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 (< 12th week), in mid-pregnancy (20th–24th weeks), and before delivery (34th–39th 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 (p = 0.01). Similar associations were observed for the HDL concentrations in mid-pregnancy (p = 0.04) and before delivery (p = 0.03). Higher triglyceride concentrations in the first trimester (p = 0.02) and before delivery (p = 0.008) were associated with LGA. Higher glycated haemoglobin (HbA1c) 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 HbA1c concentrations. Conclusions Decreased HDL and increased triglycerides during pregnancy might contribute to the development of LGA in women with type 1 diabetes.

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

Abstract 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.

\"Mitochondrial GWAS and Association of Nuclear - Mitochondrial Epistasis with BMI in T1DM Patients\"

Mitochondria are organelles whose main role is energy production and might influence obesity. They are the only organelles with their own genome. Here we have genotyped 435 patients with type 1 diabetes using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We have analyzed additive interactions between mitochondrial and nuclear variants in genes known to be associated with mitochondrial functioning (MitoCarta2.0) and confirmed and refined the results on external cohorts - Framingham Heart Study (FHS) and GTEx data. The linear mixed model analysis was performed using the GENESIS package in R/Bioconductor We have found a nominal association between rs28357980 localized to MT-ND2 and BMI (β=−0.69, p=0.056). This was confirmed on 1889 patients from FHS cohort (β =−0.312, p=0.047). Next, we have searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in SIRT3, ATP5B, CYCS, TFB2M and POLRMT genes. TFB2M is a mitochondrial transcription factor and together with TFAM creates transcription promoter complex for mitochondrial polymerase POLRMT. We have found that the interaction between rs3021088 of MT-ND2 gene and rs6701836 in TFB2M has led to BMI decrease (inter_pval=0.0241), while interaction of rs3021088in MT-ND2 and rs41542013 in POLRMT gene led to BMI increase (inter_pval=0.0004). The influence of these interactions on BMI was confirmed on external cohorts. Here, we have shown that variants in mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts. Author summary Obesity is an epidemic of our times. It is known that it results from an imbalance between energy intake and its expenditure, while mitochondria are organelles whose main role is energy production. They are the only organelles that contain their own genome. Thus, we have genotyped 435 patients with type 1 diabetes and looked on single mitochondrial variant influence as well as on additive interactions between mitochondrial and nuclear variants which might affect BMI. Our analysis has shown, that rs28357980 localized to MT-ND2 is associated with BMI. Next, we looked whether variants in this gene, which builds complex I of the electron transport chain, might interact with nuclear variants and together they modify obesity risk. We focused mainly on mitochondrial biogenesis and found that interactions between variants in TFB2M (rs6701836) or POLRMT (rs41542013) and MT-ND2 (rs3021088) affect patients BMI. TFB2M is a mitochondrial transcription factor which, together with TFAM, creates transcription promoter complex and enables transcription by mitochondrial polymerase POLRMT. The obtained results were also confirmed and refined on external cohorts - Framingham Heart Study (FHS) and GTEx data. Thus, we have shown that variations in mitochondrial genome and its interactions with nuclear variants might have an influence on BMI.

Standards of Polish Society of Gynecologists and Obstetricians in management of women with diabetes

Ewa Wender-Ożegowska1, Dorota Bomba-Opoń2, Jacek Brązert3, Zbigniew Celewicz4, Krzysztof Czajkowski5, Paweł Gutaj1, Aneta Malinowska-Polubiec5, Agnieszka Zawiejska1, Mirosław Wielgoś2 1Division of Reproduction, Poznan University of Medical Sciences, Poznan, Poland 21st Chair and Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland 3Department of Obstetrics and Women’s Diseases, Poznan University of Medical Sciences, Poland 4Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland 52nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland