[Association of polymorphisms of genes TCF7L2, FABP2, KCNQ1, ADIPOQ with the prognosis of the development of type 2 diabetes mellitus].

AIM: To study the possibility of using polymorphisms of genesTCF7L2,FABP2,KCNQ1,ADIPOQas markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk. MATERIALS AND METHODS: On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the case-control principle (case people who had diabetes mellitus 2 over 10 years of observation, and control people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.26.7 years, men 29.6%, women 70.4%), control group (n=532, mean age 56.17.1 years, men 32.7%, women 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package. RESULTS AND DISCUSSION: No significant effect of rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene, and rs6773957 of theADIPOQgene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of theTCF7L2gene are genotypes for the risk of developing T2D (relative risk RR 3.90, 95% confidence interval CI 2.316.61,p0.001; RR 1.86, 95% CI 1.422.43,p0.001, respectively). The CC genotype rs7903146 of theTCF7L2gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.290.49,p0.001). When theTCF7L2gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women. CONCLUSION: The rs7903146 polymorphism of theTCF7L2gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 4569 years during 10 years of follow-up. The association with the prognosis of the development of T2D polymorphisms rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene and rs6773957 of theADIPOQgene was not found.

[10-year risk of fractures (FRAX) in people with diabetes type 2].

AIM: To study indicators of bone mineral densit (BMD) and trabecular bone score (TBS) and to reveal the 10-year fracture risk (FRAX®) taking into account the data obtained in persons with type 2 diabetes (DM2). MATERIALS AND METHODS: A clinical study of the type of case - control. The study included 122 people with and without DM2. All persons were: questionnaires, anthropometry, densitometry, determination of TBS and fracture risk on the FRAX®. RESULTS AND DISCUSSION: Persons with DM2 who underwent a fracture had lower T-score values in all areas except the spine, unlike those with DM2, but without fracture. However, persons with DM2 had a fracture at high values of T-score in vertebrae and hips in comparison with persons without DM. Using the TBS, we did not get a significant difference in any of the examined groups. We also found no differences in the risk of recurrent fractures among women with and without DM2 using FRAX® without densitometry and FRAX® adjusted for TBS. The values of FRAX® by T-score in the group of persons with DM with fractures were significantly lower (p=0.029 for major fractures, p=0.024 for hip fractures) than in persons without DM with fractures. CONCLUSION: Persons with DM2 and fractures have higher BMD values, lower than the FRAX fracture risk values adjusted for the T-score, do not differ significantly in TBS, which determines the difficulties in diagnosis, the need to find additional methods for early diagnosis of increased fracture risk in patients with DM2.

[The prevalence of components of metabolic syndrome in the patients with diabetes melitus type 2 and mody diabetes in young people of Novosibirsk].

AIM: To estimate the prevalence of type 2 diabetes mellitus (DM2) and MODY diabetes as well as the prevalence of metabolic syndrome (MS) components for these types of diabetes in the young population of the city of Novosibirsk. MATERIALS AND METHODS: In 2013-2017 years a population survey was conducted of a random representative sample of the population of 25-45 years of both sexes, residents of one of the typical districts of Novosibirsk. WHO criteria (1999-2013) were used for the diagnosis of diabetes: fasting blood glucose ≥7.0 mmol / l after an 8-hour fasting. Also group with DM2 included persons with a fasting blood glucose level.

[Molecular genetics of maturity-onset diabetes of the young]. / Molekuliarnaia genetika MODY.

To verify the type of diabetes mellitus (DM) remains an extremely important problem in endocrinology, as along with types 1 and 2 DM there are rarer hereditary types of DM, including maturity-onset diabetes of the young (MODY). The latter is a genetic type of DM, which is characterized by an autosomal dominant inheritance. Eleven types of MODY (MODY 1 to MODY13) are identified; each is associated with mutations in the certain gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11 and ABCC8. A molecular genetic testing for suspected MODY is conducted to verify the diagnosis and to define a subtype of MODY, patient management tactics, to predict the outcome of the disease and its complications in relation to the found subtype of MODY. It is also important to seek mutation causing MODY in terms of the early detection of MODY in the first-degree relatives of a proband, appropriate therapy of the disease, and prevention of its complications.

The Impact of Hypoglycemic Therapy on the Prognosis for Acute Coronary Syndrome in Patients with Type 2 Diabetes.

The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers possible protective molecular mechanisms of various groups of drugs in ischemic cardiomyocytes.

A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2.

The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic ß-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580-1G>A substitution (IVS5 -1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro- and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method. Key words: human; maturity onset diabetes of the young; MODY2; glucokinase gene; next-generation sequencing; genetic analysis; bioinformatics.

[Erratum: The forearm fractures in patients with diabetes and without diabetes in population sample aged over 50 years (Novosibirsk) (Problems of Endocrinology (2019) 65(2) DOI: 10.14341/probl9799)].

A corrigendum on the article The forearm fractures in patients with diabetes and without diabetes in population sample aged over 50 years (Novosibirsk) by E.S. Mazurenko, S.K. Malyutina, L.V. Shcherbakova, S.V. Mustafina, T.M. Nikitenko, M. Bobak, O.D. Rymar (2018). Problems of Endocrinology 65(2). doi: 10.14341/probl9799 There was an error on the page 84 in the Table 4: symbol greater than or equal to was confuse with lower than in the table raw for menopause; symbol lower than or equal to was confuse with greater than in the table raw for total cholesterol level. The authors and editors apologize for this error. The original article has been updated.

[The forearm fractures in patients with diabetes and without diabetes in population sample aged over 50 years (Novosibirsk)].

BACKGROUND: The attention to the forearm fractures, as to osteoporotic fractures, is important for ensuring early detection of individuals at increased risk of future fractures and taking preventive measures. AIMS: To determine the frequency of a history of forearm fractures in patients with type 2 diabetes mellitus (DM2) and without diabetes, and their association with risk factors for chronic non-communicable diseases (NCD). MATERIAL AND METHODS: In 2015-2017, in Novosibirsk, a random urban population sample of males and females, 58-84 years old (n=3878), was surveyed. The study included persons who signed the informed consent to conduct the study, excluded individuals who wrote a waiver of taking blood to determine biochemical parameters. In total, the analysis included n=3393 people, 718 of them with DM2 (21.2%). Work design is cross-sectional research. The collection of information on fractures during for the last 3 years, the registration of socio-demographic data; and risk factors for NCD, a study of biochemical blood parameters. The analysis of the association of DM2 and a complex of risk factors for NCD with a chance of a forearm fracture. RESULTS: The prevalence of forearm fractures in the last 3 years did not differ in patients with DM2 compared with those examined without diabetes and was 2.4% and 2.8%, respectively (p=0.557). Men with fractures had higher cholesterol and HDL values, women had lower body mass index (BMI), compared with people without fractures. According to the results of a multivariate analysis in women, the chance of a forearm fracture is directly associated with smoking in the past, a total cholesterol level of more than 200 mg/dl and inversely associated with a BMI. In men, associations were found of the chance of a forearm fracture with an increase in the level of cholesterol. There was no evidence of DM2 with forearm fracture. CONCLUSION: The obtained data on the incidence of fractures and their association with risk factors for chronic low risk infections suggest the need for preventive measures for osteoporotic fractures, both in people with and without DM2.

[Providing of adult population of Novosibirsk with iodine].

32,7% of the population of Novosibirsk consume iodine salt. The median of iodine is revealed 106,8 mkg/l. The iodine deficiency is revealed 46,3%. It is not received an authentic difference in volumes of thyroid gland and parameters of TSH at surveyed with normal parameters of excretion of iodine in urine and at a various degree of expressiveness of iodine deficiency (p>0,05). Structural pathology of thyroid gland equally frequently meets at people with iodine deficiency and without iodine deficiency (p>0,05).

A Case of Maturity Onset Diabetes of the Young (MODY3) in a Family with a Novel HNF1A Gene Mutation in Five Generations.

Diabetes mellitus with autosomal dominant inheritance, i.e., maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus. The MODY phenotype is associated with gene mutations leading to pancreatic ß-cell dysfunction. Here, we present the clinical case of a 50-year-old proband with familial diabetes mellitus in five generations (proband, her mother, grandmother, great-grandfather, and son). This disease is most likely associated with the novel Ser6Arg mutation in the HNF1A gene, which was identified in four family members. The mutation was not detected in MODY patients (126 subjects), in patients with type 2 diabetes mellitus (188 subjects), and in a general population sample (564 subjects).

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.

OBJECTIVE: Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia. RESULTS: We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency < 1%) rs806052, rs143051164, and rs149840771 were genotyped in 126 cases of MODY, in 188 patients with type 2 diabetes mellitus (DM2), and 564 randomly selected Caucasian individuals in Russia. A heterozygous rs806052 variant was identified in one patient with DM2; c.1270T frequency was 0.003. Prevalence of rs143051164 c.844G was 0.003 in the control population and 0.004 and 0.003 in MODY and DM2 samples, respectively. Prevalence of rs149840771 c.2096A was 0.003 and 0.004 in the control population and among MODY patients, respectively. In DM2 patients, rs149840771 c.2096A was not identified. We did not detect any associations of rs806052, rs143051164, and rs149840771 with carbohydrate metabolism disorders among patients with MODY and DM2 in Russia.