Меtformin-associated maternal and neonatal outcomes in women with gestational diabetes - a retrospective cohort study.

OBJECTIVES: To assess the maternal and neonatal outcomes in women with GDM treated with metformin, medical nutrition therapy (MNT) or insulin. MATERIAL AND METHODS: The current retrospective cohort study includes data from 233 women diagnosed with GDM who gave birth between January 2017 and January 2019 at an obstetrics and gynecology hospital in Sofia, Bulgaria. Patients were assigned to three groups, according to the treatment approach - metformin group (n = 70), insulin group (n = 40), and MNT group (n = 123). Values of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) have been evaluated at diagnosis of GDM and the third trimester of pregnancy. A comparative analysis of pregnancy outcomes and short-term neonatal characteristics in the investigated groups has been performed. RESULTS: Women indicated for pharmacological treatment (metformin or insulin) had significantly higher BMI (p < 0.01), FPG (p < 0.001), and HbA1c levels (p < 0.001) at baseline. However, during pregnancy, patients treated with metformin showed a significantly lower BMI (p < 0.01), FPG (p < 0.01), and HbA1c (p < 0.01). Neonates born to metformin-treated mothers had lower birth weight compared to those born to women in the MNT and insulin groups (metformin vs MNT, p < 0.001; metformin vs insulin, p = 0.03). The lowest incidence of newborns with macrosomia and neonatal hypoglycemia has been observed in the metformin cohort. Not a single newborn with an Apgar score under 7 has been identified in the metformin group. CONCLUSIONS: According to the current analysis, women with GDM treated with metformin demonstrated better maternal and neonatal outcomes. No short-term complications in newborns have been associated with metformin use during pregnancy.

Placental Growth Factor and Pregnancy-Associated Plasma Protein-A as Potential Early Predictors of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and one of the main causes of adverse pregnancy outcomes. An early diagnosis of GDM is of fundamental importance in clinical practice. However, the major professional organizations recommend universal screening for GDM, using a 75 g oral glucose tolerance test at 24-28 weeks of gestation. A selective screening at an early stage of pregnancy is recommended only if there are maternal risk factors for diabetes. As a result, the GDM diagnosis is often delayed and established after the appearance of complications. The manifestation of GDM is directly related to insulin resistance, which is closely associated with endothelial dysfunction. The placenta, the placental peptides and hormones play a pivotal role in the manifestation and progression of insulin resistance during pregnancy. Recently, the placental growth factor (PlGF) and plasma-associated protein-A (PAPP-A), have been shown to significantly affect both insulin sensitivity and endothelial function. The principal function of PAPP-A appears to be the cleavage of circulating insulin-like growth factor binding protein-4 while PlGF has been shown to play a central role in the development and maturation of the placental vascular system and circulation. On one hand, these factors are widely used as early predictors (11-13 weeks of gestation) of complications during pregnancy, such as preeclampsia and fetal aneuploidies, in most countries. On the other hand, there is increasing evidence for their predictive role in the development of carbohydrate disorders, but some studies are rather controversial. Therefore, this review aims to summarize the available literature about the potential of serum levels of PlGF and PAPP-A as early predictors in the diagnosis of GDM.

Benefits of using a microencapsulated vitamin D delivery system in women with polycystic ovary syndrome.

OBJECTIVE: To compare and assess the efficacy of two vitamin D delivery systems (oil-based and microencapsulated) on 25-hydroxy-vitamin D (25(OH)D) levels, body mass index (BMI) and insulin resistance (IR) in women with established polycystic ovary syndrome (PCOS) and vitamin D deficiency. MATERIALS AND METHODS: A monocentric, retrospective study was conducted, using the data of 70 female patients, who visited the endocrinology department of the "Dr. Shterev" Hospital, Sofia, Bulgaria between May 2020 and September 2020. The patients were divided into two groups according to the type of vitamin D3 supplementation: either a microencapsulated liposomal form (n=35), or a conventional oil-based form (n=35). The following clinical measures were analysed and compared: BMI, serum levels of 25(OH)D, fasting plasma glucose levels, fasting immunoreactive insulin (IRI), homeostatic model assessment (HOMA) index, levels of antimullerian hormone (AMH) II generation, and testosterone. In all selected patients, these measurements were performed at baseline and 3 months after initiation of vitamin D supplementation. RESULTS: Significantly increased serum levels of 25(OH)D were observed in patients supplemented with the microencapsulated form of vitamin D3 in the third month from the beginning of therapy, compared with the control group (p=0.003). In the microencapsulated vitamin D group, there was a decrease in IRI serum levels (p=0.023), HOMA-IR (p=0.021), serum AMH (p=0.010) and testosterone levels (p=0.006). The fasting plasma glucose levels did not change significantly. CONCLUSION: The results of our study show that the patients supplemented with a microencapsulated form of vitamin D3 achieved faster compensation of 25(OH)D levels, which in turn, under equal conditions, led to significant improvement in the metabolic profile, in particular insulin sensitivity.

The Role of Placental Growth Factor in the Prediction of Carbohydrate and Thyroid Disorders during Pregnancy.

Background and objectives: To assess whether placental growth factor (PlGF) levels may have a predictive value for the onset of gestational diabetes mellitus (GDM) and thyroid dysfunction during pregnancy. Materials and Methods: This single-center retrospective analysis was conducted at the Specialized Hospital for Active Treatment in Obstetrics and Gynecology "Dr. Shterev", Sofia, Bulgaria, from December 2017 to December 2019. Using pregnant women's electronic records, we analyzed and compared the data of 412 women diagnosed with GDM and 250 women without evidence for carbohydrate disorders. Thyroid function was tested in all patients at the time of performing GDM screening. The following measurements were compared and assessed: body mass index (BMI), fasting blood glucose levels, thyroid-stimulating hormone levels (TSH), free thyroxine, and triiodothyronine (FT4 and FT3) levels, and serum placental growth factor (PlGF). The sensitivity and specificity of PlGF as a predictive marker for GDM and thyroid dysfunction were analyzed using receiver operating characteristic (ROC) curves. Results: There were no significant differences between GDM and control groups in terms of age and BMI (p > 0.05). In patients with established GDM, the PlGF corrected multiple of the median (MoM) was significantly higher compared to the control group (0.9 vs. 0.7, p < 0.001). The ROC-AUC for the prediction of GDM and thyroid dysfunction during pregnancy was 0.68 (95% CI 0.64-0.72) and 0.61 (95% CI 0.57-0.65), respectively. Conclusions: Our results underscore the potential role of PlGF as a biomarker in the prediction and diagnosis of GDM and thyroid dysfunction during pregnancy.

Gestational diabetes mellitus: a growing economic concern.

Gestational diabetes mellitus (GDM) is a common pregnancy complication. Recent epidemiological data have shown that GDM prevalence has been on the increase worldwide. GDM could lead to adverse pregnancy outcomes and is usually associated with higher costs for its treatment and management. Pharmacoeconomics has become a crucial component of the healthcare systems in recent years because of the steadily rising costs. Despite this, there are few pharmacoeconomic studies evaluating the expenses of pregnancies impacted by GDM.

Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study.

OBJECTIVES: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. The universal screening for GDM is usually performed between 24-28 weeks' gestation. This often delays the diagnosis and could increase the risk of adverse pregnancy outcomes. Some of the biochemical placental markers - pregnancy associated plasma protein A (PAPP-A) and free-ß human chorionic gonadotropin (hCG), probably could provide a diagnostic value for GDM. The aim of our study was to assess if PAPP-A and hCG values were different among pregnant women with and without GDM and respectively, to tested their place in the early GDM screening. MATERIAL AND METHODS: We conducted a retrospective, case-control study by reviewing the clinical database records of 662 pregnant women. The analysis includes the data for a two-year period. The patients included in the observation were divided into two groups - GDM group (n = 412) and Euglycemic group (n = 250). Early screening for GDМ between 9-12 weeks' gestation was performed in 173 of the women in the interventional group due to: registered fasting plasma glucose (FPG) above 5.1 mmol/L, obesity, macrosomia in previous pregnancies or family history for diabetes mellitus. The remaining 239 women underwent universal screening at 24-28 weeks' gestation. Mean serum levels of PAPP-A, hCG, FPG, and body mass index (BMI) were measured between 10-13 gestational weeks. Serum levels of PAPP-A and hCG are presented as multiples of the normal median (MoM), adjusted by maternal baseline characteristics and demographics. RESULTS: In patients who developed GDM during pregnancy, compared with the control group, we have found significantly lower MoM values of PAPP-A (p < 0.0001), higher levels of FPG (р < 0.0001) and higher BMI (р < 0.0001). Median hCG MoM was similar in both group of pregnant women. CONCLUSION: Our findings suggest that low-normal to low reference range values of PAPP-A might be associated with higher risk for GDM. PAAP-A levels can be used as an additional factor to recommend early screening for GDM.

The relationship between thyroid dysfunction during pregnancy and gestational diabetes mellitus.

INTRODUCTION: Thyroid dysfunction and gestational diabetes (GDM) are the two most common endocrine disorders that can be observed during pregnancy. Thyroid function abnormalities can be associated with insulin resistance (IR) and changes in carbohydrate metabolism. In patients with type 1 diabetes, thyroid function is usually evaluated to rule out abnormalities within a second autoimmune disease. Patients with type 2 diabetes are tested for thyroid function in view of the associated weight gain, IR, and changes in metabolism. The question arises: Should we also look for thyroid dysfunction in patients with gestational diabetes? The aim of the study was to determine whether there are abnormalities in thyroid hormone levels in pregnant women with gestational diabetes. MATERIAL AND METHODS: A monocentric, retrospective study of the Dr Shterev Hospital electronic database was performed. We analysed the medical records of 662 pregnant women, divided in two groups - 412 with GDM and 250 with normal glucose tolerance, who gave birth in the period 2017-2019. Gestational diabetes mellitus in the study group was diagnosed with a 2-h, 75-g oral glucose tolerance test (OGTT) using the International Federation of Gynaecology and Obstetrics (FIGO) and American Diabetes Association (ADA) criteria. We analysed the mean serum concentrations of thyroid-stimulating hormone (TSH); free thyroxine (FT4), free triiodothyronine (FT3), FT3:FT4 ratio, fasting plasma glucose, age and body mass index in both groups. The groups were compared using the Mann-Whitney U-test. RESULTS: In patients who developed GDM, significantly higher concentrations of TSH (p < 0.0001) and FT3 (p < 0.0001), lower concentrations of FT4 (p < 0.0001), and higher FT3:FT4 ratios (p < 0.0001) were found. CONCLUSION: The results of this pilot retrospective series reveal that high-normal to high concentration of TSH and low-normal to low concentration of FT4 as well as high FT3:Ft4 ratio could indicate increased risk of development of GDM.

Insulin-induced Lipoatrophy in a Patient on Insulin Analogue Therapy: a Case Report.

Insulin-induced lipoatrophy is a rare skin complication in patients with diabetes mellitus. It is characterized primarily by localized subcutaneous atrophy of the fatty tissue at the site of frequent insulin injection. We report a clinical case of a 38-year-old woman with lipoatrophy, developed during treatment with insulin analogues. Lipoatrophic zone formation began 3 months after the treatment was initiated. A lipoatrophic defect developed on the thighs and the upper outer arms, resulting from repeated insulin injections at the same site. Regarding lipoatrophic areas, treatment with topical administration of corticosteroids was attempted but without a significant clinical effect. The best prevention from lipoatrophy development is education of patients regarding rotation of insulin injection sites and more frequent needle change.

Autoimmune Polyglandular Syndrome Type 2 and Pregnancy.

Autoimmune polyglandular syndromes are combinations of various endocrine and nonendocrine autoimmune diseases, as well as the presence of elevated organ-specific antibody titers. We present a clinical case of a 41-year-old pregnant patient with type 2 autoimmune polyglandular syndrome, combining Addison's disease, Hashimoto's thyroiditis and hypogonadism. The pregnancy was achieved after the use of assisted reproductive technology. During the pregnancy the patient was strictly monitored. Glucocorticoid and mineralocor-ticoid replacement therapy was adjusted according to the electrolyte profile and general condition of the patient. Management during pregnancy was difficult due to fluctuations in electrolyte levels, thyroid hormones and orthostatic manifestations. Prior to delivery adrenal crisis occurred, but the condition was successfully managed. No complications were reported for the mother and the newborn.