Alena Viktorovna Tiselko

BACKGROUND: Neonates with excessive body fat deposition are at increased risk of adverse short- and long-term outcomes. The potential of fractional fetal thigh (TVol) and arm (AVol) volume assessment to predict fetal body composition at birth, including but not limited to neonates of mothers with diabetes mellitus, is to be investigated. AIM: The aim of this study was to investigate the association between the extended fetal biometry measurements, based on the calculation of fetal fractional limb volumes, the neonatal body composition, and the development of neonatal hypoglycemia. METHODS: This single-center cohort study included patients with singleton pregnancies divided into the study groups: pregestational diabetes mellitus, gestational diabetes mellitus, and no carbohydrate metabolism disorders. Routine fetal biometry and TVol and AVol assessment were performed within 7 days before delivery. Body fat mass at birth was calculated using the Catalano et al. (1995) equation. RESULTS: The study included 46 patients with diabetes mellitus (pregestational, n = 32; gestational, n = 14) and 18 healthy control individuals, as well as their children. In newborns with diabetic fetopathy, the percentage of body fat was the highest — 25.0 [22.1; 26.1]% (p 0.001). Neonates in the pregestational diabetes mellitus group had a higher weight-for-length Z-score (INTERGROWTH-21st) — 1.253 [0.663; 2.058] (p = 0.001), in the gestational diabetes mellitus group — 0.247 [0.014; 0.411] (p = 0.001), and in the control group — 0.485 [0.059; 0.887] (p = 0.004). The percentage of body fat mass was strongly associated (p 0.001) with neonatal weight (r = 0.706) and its Z-score (r = 0.840), the weight-for-length ratio and its Z-score (r = 0.843), TVol (r = 0.639), and AVol (r = 0.532). The percentage of body fat mass did not correlate with the estimated fetal weight (r = 0.135, p = 0.288). A linear regression model including TVol and gestational age at birth had r2 = 0.64 (p 0.001) for body fat mass prediction. Generalized linear models identified pregestational diabetes mellitus as independent risk factor (p 0.001) for higher body fat mass percentage with comparable TVol. For neonatal hypoglycemia prediction, the birth weight Z-score (sensitivity 66.7%, specificity 70.0%) and the weight-for-length Z-score (sensitivity 66.7%, specificity 75.0%) were unreliable estimates, whereas the percentage of body fat mass had better performance (sensitivity 70.8%, specificity 80.0% at a percentage of greater than or equal to 20.2%). CONCLUSION: The accuracy of fetal adiposity detection and assessing the risk of neonatal hypoglycemia can be improved by using fetal fractional limb volume measurements. TVol is a sonographic predictor for excessive fat deposition, which can be used for body fat mass calculation, while parameters measured during routine fetometry poorly reflect the distribution of fat tissue in the fetus.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. PCOS is a leading cause of infertility, ovulatory dysfunction, menstrual irregularities and a well-known risk factor for prediabetes, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Depending on the clinical manifestations, patient’s age and reproductive life plans the goals and strategies of PCOS treatment may differ. There is currently clinical evidence of the positive effects of metformin on ovulatory function, menstrual cycle regularity, fertility and pregnancy outcomes in patients with PCOS. These results related to metformin’s effects on insulin resistance, hyperinsulinemia and hyperandrogenism. In patients with PCOS and prediabetes or T2DM metformin improves glycemic control and also exerts a number of pleiotropic effects that reduce the risk of carbohydrate metabolism disorder progression and the development of CVD. In PCOS, ovarian dysfunction contributes to a cascade of metabolic and vascular changes even in the absence of T2DM. Therefore, the indications for metformin in patients with PCOS may extend beyond the glycemic control. This article is a summary of the expert council on the issues of managing adult patients with PCOS, taking into account current knowledge of reproductive, metabolic, and cardiovascular risks. It also contains the key data on the use of metformin in women with PCOS in various clinical situations and the legal aspects of metformin use in modern clinical practice.

Recent research has demonstrated the effectiveness of continuous glucose monitoring systems in improving obstetric and perinatal outcomes in women with diabetes mellitus. Furthermore, these systems have opened up opportunities for stratifying patients based on their glycemic profiles, known as glucotypes, which, in turn, enables a more personalized approach to predicting complications and choosing treatment strategies. This article was aimed to analyze glycemic profile data obtained, using continuous glucose monitoring systems in pregnant women with pregestational diabetes mellitus, in order to study predictors of obstetric and perinatal complications, according to the available literature. We conducted a systematic review of publications from MEDLINE, PubMed, EMBASE and CSCD databases from 2005 to 2024. Fourteen studies that met the inclusion criteria were included in the analysis. The primary endpoints were continuous glucose monitoring data, glycated hemoglobin levels, and the incidence of preeclampsia, preterm birth, macrosomia, and neonatal hypoglycemia. Continuous glucose monitoring has been shown to be associated with lower glycated hemoglobin levels, increased time spent in the target glucose range, and decreased incidence of macrosomia, neonatal hypoglycemia, and neonatal intensive care unit admissions. The use of new methods of glycemic profile assessment such as glucotype allocation based on continuous glucose monitoring data opens up new opportunities for personalized pregnancy management. Continuous glucose monitoring can significantly improve glycemic control in pregnant women with pregestational types of diabetes mellitus and optimize insulin therapy, while helping to reduce the incidence of adverse obstetric and perinatal outcomes. Stratification by glucotype may be a promising avenue for personalization of therapy.

BACKGROUND : Women with type 1 diabetes mellitus (DM) have a high frequency of menstrual irregularities and perinatal complications. New methods for monitoring the glycemic profile provide opportunities to analyze the effectiveness of insulin therapy regimens in maintaining the reproductive health of these patients. AIM: The aim of the study was to assess the relationship between glycemic profile patterns, pro- and antioxidant statuses, and ovarian reserve parameters in type 1 DM patients. MATERIALS AND METHODS : This study included 60 type 1 DM women, of whom 30 patients aged 33.0 [30.0; 35.0] years used the multiple insulin injections (MII) regimen (Group 1). In this group, patients were divided into two subgroups: not exceeding the percentage of hyperglycemia above the target range for more than 35% of the day (Group 1A) and exceeding this range (Group 1B). The continuous subcutaneous insulin infusion (CSII) regimen was administered to other 30 patients (Group 2). They were subdivided identically into Groups 2A and 2B. We analyzed continuous glucose monitoring data using the FreeStyle Libre Flash Glucose Monitoring System and evaluated blood malonic dialdehyde level, catalase activity and 3-nitrotyrosine level, as well as ovarian volume, antral follicle count, anti-Müllerian hormone and follicle-stimulating hormone levels. RESULTS : We found no differences in the time in range in Groups 1A and 2A. The HbA1c level was higher in the time above range group of women using MII. Blood 3-nitrotyrosine level in Group 1B was 161.4 [110.6; 232.1] nmol/l and differed from that in Group 2B (42.4 [19.1; 64.9] nmol/l; pCONCLUSION : Preliminary data were obtained on the relationship between hyperglycemia exceeding 7.8 mmol/l for more than 35% of the day with oxidative stress parameters, sRAGE levels, and a tendency towards an increase in the antral follicle count in women with type 1 DM.

The present article contains the newest ant the most actual version of clinical recommendations “Gestational diabetes mellitus” of the Russian Ministry of Health. This document has been confirmed for the period from 2024 until 2026 year. Gestational diabetes mellitus is widely known as onset of hyperglycaemia during pregnancy that does not responds to criteria of manifesting diabetes mellitus (DM). The time of next revision is 2026 year or earlier if new evidentiary material appear. The present version of clinical recommendation has been created due to collaboration between Russian Association of Endocrinologists and Russian Society of Obstetricians and Gynecologists. The document is finally approved by scientific and practical Council of the Russian Ministry of Health.

Background: Chronic hyperglycemia and abnormal glucose variability are established risk factors for perinatal complications. Abnormal fetal growth and diabetic fetopathy can be associated not only with carbohydrate metabolism disorders, but also with impaired production of cytokines, chemokines, and growth factors that regulate intercellular interactions. Aim: The aim of this study was to evaluate cytokine and growth factor levels in the blood serum of pregnant women with type 1 diabetes mellitus and in umbilical cord blood of their neonates, as well as assessing the associations of these levels with the development of fetal macrosomia and diabetic fetopathy. Materials and methods: This prospective study included 88 women with a singleton pregnancy and cesarean delivery. All the patients provided informed consent for participation. The study groups comprised individuals with type 1 diabetes mellitus (n = 32) and non-impaired glucose tolerance (n = 56). The levels of interferons alfa 2 and gamma, monokine induced by interferon-gamma, interleukin-1α, -1β, -2, -3, -4, -5, -6, -7, -8, -9, -10, -13, -15, -16, -17, -18, interleukin-1 receptor antagonist, interleukin-2 receptor alpha subunits, p40 and p70 subunits of interleukin-12, monocyte chemotactic protein-1, -3, macrophage inflammatory protein-1α, -1β, leukemia inhibitory factor, macrophage ingibitory factor, nerve growth factor beta, stem cell factor, cutaneous T-cell-attracting chemokine, growth-regulated oncogene alpha, hepatocyte growth factor, stem cell growth factor beta, stromal cell-derived factor-1 alfa, interferon gamma inducible protein 10, platelet-derived growth factor-bb, vascular endothelial growth factor, basic fibroblast growth factor, eotaxin, chemokine ligand 5, and macrophage, granulocyte, and granulocyte/macrophage colony-stimulating factors, tumor necrosis factor alfa and beta, and tumor necrosis factor-related apoptosis-inducing ligand were measured with multiplex immunoassay in the blood serum of women at 36–40 weeks of gestation and in the umbilical cord blood serum of their neonates. Results: Cytokine levels varied widely in the both study groups. Women with type 1 diabetes mellitus had higher levels of interleukin-1β, -6, -17, basic fibroblast growth factor, macrophage inflammatory protein-1α, -1β, and lower levels of interleukin-1ra compared to the control group. Their neonates had higher levels of interleukin-6, -8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1α, -1β. Higher levels of interleukin-1β, -6, -17, and basic fibroblast growth factor in the blood serum of the women were associated with time in range less than 70% and the development of diabetic fetopathy. Time in range was inversely associated with the interferon gamma / interleukin-5 (ρ = −0.531; p = 0.013), interferon gamma / interleukin-10 (ρ = −0.441; p = 0.045), interleukin-2 / -10 (ρ = −0.473; p = 0.030), interleukin-1β / -10 (ρ = −0.561; p = 0.008), interleukin-1β / -1ra (ρ = −0.635; p = 0.002), and interleukin-6 / -10 (ρ = −0.540; p = 0.012) ratios. Conclusions: Cytokine profile alterations were the most pronounced in pregnant women with non-target time in range values and in those with diabetic fetopathy development. Serum cytokine levels correlate with glycemic profile parameters but are considered non-specific markers of pregnancy complications.

Background: Type 1 diabetes mellitus and endometriosis significantly reduce the quality of patient’s life and hinder the implementation of reproductive plans. Studying the features of the clinical course of endometriosis in patients with type 1 diabetes mellitus will help in the development of new effective and safe therapeutic strategies and diagnostic methods. Aim: The aim of this study was to analyze the clinical course of the diseases, hormonal status and blood vitamin D (25-hydroxycalciferol) levels in patients with type 1 diabetes mellitus combined with endometriosis. Materials and methods: This clinical prospective study included 339 women, of whom 79 patients were with type 1 diabetes mellitus combined with endometriosis (mean age 31.7 ± 5.0 years), 51 patients were with endometriosis (mean age 31.4 ± 3.7 years), and 209 patients were with type 1 diabetes mellitus (mean age 30.2 ± 4.9 years). The control group consisted of 31 healthy women of reproductive age. The immunochemiluminescent method was used to determine the blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol (days 2–5 of the menstrual cycle), progesterone (days 20–23 of the menstrual cycle) during three consecutive menstrual cycles, and the blood serum level of glycated hemoglobin was also studied in patients with type 1 diabetes mellitus. The diagnosis of endometriosis in all patients was confirmed based on laparoscopic surgery with verification by histological examination. Results: When assessing the levels of gonadotropins, prolactin, and anti-Müllerian hormone in patients with endometriosis, a decrease in blood anti-Müllerian hormone level was noted in comparison with the other study groups. The levels of gonadotropins and prolactin in patients in all of the study groups were comparable. In all of the study groups, the progesterone level on days 20–23 of the cycle was lower than in the control group. The concentration of vitamin D (25-hydroxycalciferol) in the patients’ peripheral blood in all of the study groups was lower compared to the control group, with the minimum value of 16.3 ± 4.1 ng/ml found in the group of patients with type 1 diabetes mellitus combined with endometriosis. In patients with type 1 diabetes mellitus and in those with the disease combined with endometriosis, no differences were found between the age of onset of type 1 diabetes mellitus and its duration, the total daily insulin dose, and the insulin dose per kilogram of the patient’s weight. The glycated hemoglobin level was higher in the group of patients with type 1 diabetes mellitus. When distributing patients by the grades of endometriosis prevalence, it was found that grades III and IV were more common in patients without type 1 diabetes mellitus. The incidence of deep infiltrating endometriosis was higher in the group of patients with endometriosis only, as was the number of reoperations. Conclusions: The asymptomatic preclinical period of endometriosis in patients with type 1 diabetes mellitus may lead to untimely and erroneous diagnosis and delayed treatment of the disease. In patients with type 1 diabetes mellitus onset in puberty and suffering from endometriosis, the risk of vascular complications increases and the ovarian reserve decreases, which requires the implementation of reproductive goals as early as possible. When choosing therapy for endometriosis in patients with type 1 diabetes mellitus, the presence of vascular complications should be taken into account.

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

Background Despite enormous advances in diabetes treatment, women with type 1 diabetes mellitus (DM) still experience delayed menarche, menstrual irregularities, fewer pregnancies, and a higher rate of stillbirths compared to women without the disease. Due to the fact that type 1 DM occurs at a young age, the preservation of reproductive health is one of the most important goals of treatment. Aims The aim of this study was to evaluate the relationship between different glycemic profiles and changes in the pro-oxidant-antioxidant balance and ovarian follicular apparatus in reproductive-age patients with type 1 DM. Methods We examined 50 reproductive-age (19–38 years) women with type 1 DM with a disease duration of at least ten years. Carbohydrate metabolism was assessed with the continuous glucose monitoring (CGM) system and glycated hemoglobin (HbA1c) concentration measurement. CGM was performed using the FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, UK). In each patient, malondialdehyde level, catalase activity and 3-nitrotyrosine level in the blood serum were determined. To assess the ovarian function, we measured the ovarian volume, the antral follicle count, and the serum levels of anti-Müllerian hormone and follicle-stimulating hormone. All patients were divided into four groups (glucotypes) based on the CGM results. Group 1 included type 1 DM patients with satisfactory compensation of carbohydrate metabolism; group 2 consisted of patients with frequent hypoglycemic conditions and pathological glucose variability; group 3 included individuals with prolonged hyperglycemic conditions and maximum HbA1c levels; and group 4 comprised patients with the glycemic profile characterized by all the presented types of dysglycemia (intermittent glycemia). Results We revealed a negative correlation between serum catalase activity and time of hypoglycemic conditions in patients with type 1 DM based on the CGM results (r_s = −0.47, p < 0.01). In group 4 (intermittent glycemia), patients demonstrated the lowest serum catalase activity and increased serum 3-nitrotyrosine level, while in group 3, women with chronic hyperglycemia (HbA1c 8.4 [8.1; 9.9]%; 68 [65; 85] mmol/mol) had a moderate change in antioxidant defense and oxidative stress parameters. Correlation analysis of ovarian volume, the antral follicle count, and the serum anti-Müllerian hormone level in type 1 DM women with different glycemic profiles established a negative relationship (r_s = −0.82, p < 0.05) between the antral follicle count and glucose variability in group 1, a positive relationship (r_s = 0.68, p < 0.05) between ovarian volume and glucose variability in group 2, and a positive relationship (r_s = 0.88, p < 0.05) between ovarian volume and time of hypoglycemic conditions, which, according to the CGM results, amounted to a critical value of 57.5 [40.0; 82.0]%. Conclusions The data obtained indicate the relationship between the ovarian volume, serum anti-Müllerian hormone level, the antral follicle count and oxidative stress parameters not only in patients with hyperglycemia, but also in those with hypoglycemic conditions, as well as with pathological glucose variability.