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.

Hypothesis/aims of study. The ongoing global problem of health care and medical science is an associated increase in the frequency of endocrine and metabolic diseases and cancer, including in women of childbearing age. Thus, the frequency of diabetes in the population has been growing rapidly for many years. Similar trends were observed in the dynamics of the frequency of cancer pathology, especially of breast cancer, which is one of the leading places in the structure of the cancer incidence in the female population. It is known that diabetes and related insulin resistance have a very negative effect on the female reproductive function, leading to hyperplastic processes of the mammary glands. The least studied problem so far is understanding the mechanisms of development, timely diagnosis, prevention, and treatment of fibrocystic mastopathy, the proliferative forms of which underlie malignant tumors, while its atypical variations are regarded as a precancerous condition. It is likely that the pathogenesis of hyperplastic processes in the mammary gland and the risk of neoplastic transformation in disorders of carbohydrate metabolism may have special factors. The actual problem is the development of a method for pathogenetically substantiated correction of fibrocystic breast disease. This is essential for the development of pharmacological strategies for secondary prevention of breast cancer and, in this regard, it is of great interest to study application possibilities of biguanides. The purpose of the present study was to conduct a comparative assessment of the effectiveness of metformin therapy in fibrocystic mastopathy patients with and without insulin resistance. Study design, materials, and methods. The study involved 120 women, aged 18 to 40 years inclusive, with clinical and / or ultrasound signs of fibrocystic breast disease. According to the results of calculating HOMA index, patients were divided into two groups: the first group comprised 66 patients with insulin resistance (HOMA > 2.5) and the second group consisted of 54 patients with no insulin resistance (HOMA < 2.5). Assessment of mastalgia was performed using the Visual Analogue Scale. Breast ultrasound examination was performed on days 5 to 7 of the menstrual cycle. For the purpose of quantitative image analysis of the breast parenchyma, the following parameters were evaluated: a) thickness of the parenchyma (fibroglandular zone); b) diameter of the milk ducts; c) echogenicity. All patients received metformin at a dose of 1500 mg per day. Dynamic control of the clinical picture of the disease, as well as of mammographic breast parenchymal pattern, was performed after 3 and 6 months from the start of therapy. Results and conclusion. After 6 months of therapy, there was a decrease in the frequency of mastalgia, and significant changes in breast ultrasound picture were observed. The data obtained on the positive effect of metformin on clinical mastitis and structural changes in the mammary parenchyma in patients with mastopathy allow considering such an approach as a promising therapeutic strategy in this pathological association.

A little studied question is the development mechanism, timely diagnostics, treatment and prevention of the fibrocystic breast disease at patients with insulin resistance. One of the possible perspective directions of pathogenetic impact on tissues of a mammary gland at the mastopathy associated with a giperinsulinemiya and insulin resistance is use of metformin. Now clinical trials on use of metformin at cancer of mammary glands continue. Data on use of medicines of this group at patients with fibrocystic breast disease in domestic and foreign literature are absent.Objective:assessment of influence of metformin on clinical displays of fibrocystic breast disease and ultrasonic characteristics of a parenchyma of mammary glands at patients with insulin resistance.Materials and methods.As therapy of fibrocystic breast disease patients received metformin in a dose of 1500 mg a day. Dynamic control of a clinical picture of a disease and ultrasonic indicators of a parenchyma of a mammary gland carried out in 3 and 6 months from the beginning of therapy.Results and conclusion.In 6 months of therapy there was a reliable decrease in frequency of a mastalgiya, change of an ultorasound picture of mammary glands: echogenicity of a parenchyma of mammary glands – became sredeny in 95,9% of cases, there was a reliable reduction of thickness of a parenchyma of mammary glands (from 15.5 mm to 10. 5 mm) and diameter of lacteal channels (from 1.7 mm to 0.9 mm). The obtained data on positive influence of metformin on the clinical course of mastopathy and structural changes of a parenchyma of mammary glands at patients with fibrocystic breast disease and insulin resistance allow to consider similar approach as the perspective direction of pathogenetic influence at such pathological association.

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Diabetic mastopathy (DMP) is a rare fibrotic disease of the mammary gland (less than 1 % among benign diseases). It was first described in 1984 by Soler & Khardori in women who have suffered from type 1 diabetes mellitus for a long time. Clinically, DMP can manifest as single or double-sided, palpable, movable, painless seals. Often, DMP is a random finding in a mammographic examination of asymptomatic patients. At the same time, radiological signs are more often non-specific. When ultrasound examination of the mammary gland with DMP can be visualized hypoechoic formations with fuzzy, uneven contours, heterogeneous structure. Clinical, ultrasound and radiological manifestations of DMP are often associated by specialists with malignancy, which leads to unnecessary invasive procedures. In this regard, of interest is the clinical case of DMP in a woman of reproductive age with type 1 diabetes, repeated trepanobiopsy of the breast. The described clinical observation represents the case of repeated invasive intervention, which proves the connection between the long-term decompensation of type 1 diabetes that occurred in the juvenile age and the progression of the pathological process in the mammary glands under hyperglycemia.