Diabetic nephropathy in type 1 diabetes and pregnancy. Modern view of the problem

Diabetic nephropathy (DN) is specific kidney damage in patients with diabetes mellitus. DN develops relatively often in pregestational diabetes patients (5,9-26%) and stills one of the main limitations for successful pregnancy in this patients’ group. Advanced DN increases risks of poor pregnancy outcomes for women and fetuses including chronic kidney disease (CKD) progression, high rate of preeclampsia, preterm deliveries, Cesarean sections, perinatal mortality and neonatal morbidity. At the same time there are more and more successful pregnancies with advanced DN in the wold.In our paper we systematize global experience of planning and management pregnancies with type 1 diabetes and DN in different stages of renal impairment. We discuss role of nephroprotective therapy in preconception care, achievement and maintaining blood pressure goals, multidisciplinary team care for improvement pregnancy outcomes in type 1 diabetic women with DN

Endometriosis-associated pain and new therapeutic options: A review

Pelvic pain is one of the most common and significant clinical symptoms of endometriosis. The complex pathogenesis and paradoxical nature of endometriosis-associated pain, its chronicity and centralization, a marked decrease in the quality of life of patients, the lack of an "ideal" and effective remedy with no limitation for all patients, as well as the progressive and recurrent nature of the disease are factors that determine the need for novel, additional therapeutic options. The pain mechanisms in endometriosis and the potential pathogenetic effects of trans-resveratrol and indole-3-carbinol on various aspects of endometriosis-associated pain are addressed based on the literature sources presented in electronic databases PubMed, CyberLeninka, and Google Scholar. The described pharmacological properties of the compounds suggest that the combined use of trans-resveratrol and indole-3-carbinol is a pathogenetically justified and promising treatment for complex endometriosis-associated pain

Molecular and morphological peculiarities of chronic placental insufficiency formation caused by different types of diabetes mellitus

Рathogenesis of the chronic placental insufficiency is largely determined by the type of diabetes mellitus and the degree of its compensation. Trophic function failure of placenta changes its hormonal activity, formation of respiratory disorders and development of oxidative stress. The histological structure of placentas among patients with type 1 diabetes mellitus (T1D) is represented by reduced chorionic villi dimensions of all levels. Stromal edema and increased number of mesenchymal stromal cells are found in the stem and intermediate villi, and hypervascularisation and thickening of syncytiocapillary membranes are detected in terminal villi. In type 2 diabetes mellitus (T2D), the histological structure of the placenta may be represented as a premature maturation and abnormal immaturity of the villous tree with focal fibrosis of villi stroma, hypervascularisation of villi, abundance of syncytial nodules and infarction in the subchorial space. The peculiarity of the placenta structure in gestational diabetes mellitus is predominantly an intermediate immature type of development with angiogenesis abnormality. Angiogenesis processes failure and endothelial dysfunction in chorionic villi associated with hyperglycaemia change the permeability of cell membranes, transferring cells to anaerobic respiration. Metabolic imbalance in the placenta causes the development of diabetic micro-angiopathy in the fetal-placental complex, antenatal hypoxia and negative perinatal outcomes

Evaluation of glycaemic profile variability as a basis for insulin therapy strategy in pregnant women with type 1 diabetes

BACKGROUND: Patients with any form of diabetes during pregnancy should achieve the target (close to physiological) values of glycaemia, the main condition for a safe course and outcomes of pregnancy. To accomplish this task, effective and safe methods of insulin therapy should be selected. AIM: To determine the glycaemic profile and pregnancy outcomes in women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII). METHODS: A continuous glucose monitoring (CGM) of 100 pregnant women with type 1 diabetes treated with CSII and 100 women treated with MII was conducted to assess the effectiveness of these insulin therapy regimens in achieving target blood glucose values. RESULTS: HbA1c levels were significantly lower during the first, second, and third trimesters in patients treated with CSII than those treated with MII. Glucose variability has already improved since the second trimester of pregnancy in women treated with CSII, which was not observed in those treated with MII. The period of hyperglycaemia according to the results in pregnant women treated with CSII was 25 [13; 38] %, which was lower than those treated with MII, 41 [18; 54] %. No risk of obstetric and perinatal complications was observed with the duration of the hyperglycaemic state of <25% of the CGM time, whereas the risk of neonatal hypoglycaemia appeared with the duration of the hypoglycaemic state of a mother with type 1 diabetes of >0.2%. The relationship between glucose variability in terms of MAGE and MODD and the risk of developing macrosomia has been observed, and the dependence of glucose variability (MODD and CONGA) and the risk of neonatal hypoglycaemia and preeclampsia have also been confirmed. CONCLUSION: Comprehensive assessment of the glycaemic profile when using CSII, confirmed the advantages of using CSII in pregnant women with type 1 diabetes to achieve the target glycaemia values, to reduce glucose variability and duration of hypoglycaemic episodes, which led to decreased frequency of obstetric and perinatal complications

In vitro fertilization as a method of infertility treatment in women with type 1 diabetes mellitus

Some patients with type 1 diabetes have anovulation, tubal occlusion, male factor and other causes of infertility which require IVF procedure. We examined 20 women with type 1 diabetes, in which pregnancy occurred as a result of ART, at the stage IVF protocol planning, during pregnancy course and delivery. One of the patients underwent IVF procedure twice. Mean age of the patients who applied to the Department of assisted reproductive technologies was 33±6 years, duration of infertility varied from 3 to 15 years. Two patients were performed donor oocytes transfer (patients with Turner Syndrome and Swyer Syndrome). In 70% of patients the method of CSII was used. Assessment of carbohydrate metabolism was based on the level of glycated hemoglobin A1c (HbA1c), plasma glucose level measured at least 8 times a day and results of continuous glucose monitoring (CGM). 18 singleton pregnancies and three multiple gestations (dichorionic diamniotic twins) occurred as a result of IVF. In 12 women delivery occurred on the 37–39th weeks of gestation, in 9 patients pregnancy was terminated on the 34–36th weeks. In all the cases it was live birth. Birth weight above the 90th percentile had 6 newborns

Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body

Genetic and Phenotypic Factors Affecting Glycemic Response to Metformin Therapy in Patients with Type 2 Diabetes Mellitus

Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist–hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment