The present study reports on the frequency and the spectrum of genetic variants causative of monogenic diabetes in russian children with non-type 1 diabetes mellitus. The present study included 60 unrelated russian children with non-type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were screened using whole-exome sequencing (WeS) in a panel of 35 genes causative of maturity onset diabetes of the young (ModY) and transient or permanent neonatal diabetes. Verification of the WeS results was performed using Pcr-direct sequencing. a total of 38 genetic variants were identified in 33 out of 60 patients (55%). The majority of patients (27/33, 81.8%) had variants in ModY-related genes: GCK (n=19), HNF1A (n=2), PAX4 (n=1), ABCC8 (n=1), KCNJ11 (n=1), GCK+HNF1A (n=1), GCK+BLK (n=1) and GCK+BLK+WFS1 (n=1). a total of 6 patients (6/33, 18.2%) had variants in ModY-unrelated genes: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1) and SLC19A2 (n=1). a total of 15 out of 38 variants were novel, including GCK, HNF1A, BLK, WFS1, EIF2AK3 and SLC19A2. To summarize, the present study demonstrates a high frequency and a wide spectrum of genetic variants causative of monogenic diabetes in russian children with non-type 1 diabetes mellitus. The spectrum includes previously known and novel variants in ModY-related and unrelated genes, with multiple variants in a number of patients. The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in russian children may begin with testing for ModY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to ~50% of the cases and highlighting the efficiency of using WES in non-GCK-ModY cases.
В связи с ростом заболеваемости сахарным диабетом (СД) в последние годы увеличилось число женщин репродуктивного возраста, страдающих этим заболеванием. Более 40 лет известно о негативном влиянии гипергликемии на рост и формирование плода, течение и исходы беременности [1-4]. Как хроническая, так и эпизодическая гипергликемия у матери приводит к формированию гиперинсулинемии у плода-основной причины формирования диабетической фетопатии. Для улучшения течения и исхода беременности у женщин с СД необходимо дости-жение содержания глюкозы в крови, соответствующего физиологической беременности. С целью уточнения гликемического профиля при физиологической беременности был проведен метаанализ, включающий 12 крупных исследований профиля глюкозы при физиологической беременности [5]. По результатам анализа, максимальная концентрация глюкозы после приема пищи во время беременности наступает на 69,4±23,9-й минуте. Средний уровень гликемии натощак составил 3,9±0,4 ммоль/л, через 1 ч после приема пищи-6,1±0,7 ммоль/л, через 2 ч
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.
The main ideas about the pathogenesis of ovarian dysfunction in women with diabetes mellitus (DM) type 1 are presented. The role of increased opioid and dopaminergic tone in the pathogenesis of reducing the synthesis of the gonadotropin-releasing hormone by the hypothalamus in women with type 1 diabetes was analyzed. Presented the data of relationship between ovarian hormonal insufficiency in women with type 1 diabetes with possible damage of positive feedback mechanism of the ovaries and the pituitary gland, which intactness is necessary for the maturation of the dominant follicle and ovulation. The results of studies, suggested that the high doses of exogenously administered insulin in type 1 DM lead to stimulation of androgen synthesis in teca cells and ovarian stroma and the development of ovarian hyperandrogenemia, as well as polycystic ovary syndrome, are reduced. In addition to exogenous hyperinsulinemia, in the pathogenesis of ovarian dysfunction, the value of the deficiency of endogenous insulin, leading to a violation of steroidogenesis in the tissues of the ovary and anovulation, is proved. The role of insulin deficiency and hyperglycemia in the development of metabolic stress lead to ovarian dysfunction in patients with type 1 diabetes was analyzed.
Gestational diabetes mellitus (GDM) has been declared as one of the pandemics of our time and its prevalence is 520% in the European population. It causes the search for new pathogenetic risk factors in order to develop effective measures for the prevention and treatment of this disease. The intestinal microbiota plays an important role in maintaining the basic functions in the human body metabolic, protective and trophic, and it undergoes significant changes during pregnancy. It has now been proven that dysbiosis alters intestinal metabolism and can lead to the development of diabetes. The direct relationships between intestinal microflora species and circulating levels of insulin, triglycerides and very-low-density lipoproteins were found. In a number of studies, associations of various concentrations of intestinal microbiota metabolites with the probability of developing GDM were analyzed. Studies conducted in a group of women with complicated pregnancy revealed changes in the diversity and structure of the intestinal microbiota in women with preeclampsia and arterial hypertension. Therefore, all authors emphasize the need for studies that expand our understanding of the relationship of various intestinal microbiota disorders with the risk of developing GDM and its specific progressing.
Hypothesis/aims of study. The adverse effects of type 1 diabetes mellitus on the female reproductive system have been proved by many studies. There is still conflicting literature on the impact of diabetes and other factor compensation on ovarian function in women with type 1 diabetes mellitus. Study design, materials and methods. The current analysis was undertaken to study the effects of diabetes compensation on ovarian function in women with type 1 diabetes mellitus. In order to this, 180 individuals aged 20 to 40 years were examined. The main group consisted of 112 diabetic patients with primary ovarian insufficiency, the comparison group included 68 women with type 1 diabetes mellitus and a normal ovulatory cycle. After 18–24 months following the therapy aimed to compensate diabetes, 63 patients with ovarian insufficiency were re-examined. The examination included determination of blood glucose, glycated hemoglobin (HbA1c), FSH, LH, prolactin, estradiol, total and free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, dihydrotestosterone, progesterone, and sex hormone-binding globulin (SHBG) levels, as well as ultrasound examination in the first and second phases of the menstrual cycle. Results. Association of ovarian insufficiency with HbA1c level and the dose of insulin was found. Patients in the main group experienced a decrease in FSH and SHBG levels, an increase in the ovarian volume and the number of antral follicles compared to those in diabetic patients with a normal ovulatory cycle. In patients with decompensated diabetes and ovarian insufficiency, after the compensation of diabetes, the recovery of the ovulatory cycle was observed in 61.8 % of cases. Conclusion. Ovarian function in women with type 1 diabetes mellitus depends on HbA1c level and the dose of insulin. Diabetes compensation in women with type 1 diabetes mellitus contributes to the recovery of ovulation in 61.8 % of cases.
Oxidative stress (OS) plays an important role in embryo development, implantation, placentation, fetal development and labour. Diabetes mellitus (DM) is associated with an increase in OS processes. However, the expression of OS biomarkers in pregnant women with DM remains unclear. Based on a literature review, the features of the pro- and anti-oxidant systems of pregnant women with different types of DM have been established. Pregnancy in patients with DM has been shown to be characterised by an activation of OS processes. This leads to an overexpression of free radicals (peroxynitrite), toxic derivatives (malonic dialdehyde, 8-isoprostane) and specific enzymes (asymmetric dimethylarginine, catalase) and a decrease in the synthesis of antioxidants (superoxide dismutase, glutathione peroxidase and uric acid). The modified expression of these biomarkers is observed both in the blood and the placenta of pregnant women. These disorders can cause an unfavourable course of pregnancy, abnormal development of the placenta and development of adverse perinatal outcomes in pregnant women with DM. Nevertheless, given the inconsistency of data obtained, further scientific studies are needed to clarify this issue.
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