Neonatal diabetes mellitus (NDM) develops within the first 6 months of life. It occurs with a frequency of 1 cases per 300,000 - 500,000 newborn infants. Pathogenesis of NDM involves over 10 different genes. Of greatest clinical significance are mutations in KCNJII and ABCC8 genes responsible for the activity of ATP-dependent potassium channels and regulating their activation. It was shown that the intake of oral sulfonylurea (SU) preparations results in the closure of these channels and thereby stimulates the release of insulin from beta-cells. For this reason, SU therapy can be applied as an alternative to insulin injections. SU preparations ensure the efficacious control of metabolic processes and substitute insulin in the majority of the cases of transient and permanent NDM associated with mutations in KCNJII and ABCC8 genes. The original observations demonstrating the relationship between the type of mutation in the KCNJII gene and the dose of SU preparations are presented.

Aim. To compare HLA II allele and genotype frequency distribution in type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AIT) with that in isolated T1DM. Materials and Methods. A total of 92 T1DM patients were subdivided into two groups. The first group comprised 54 patients with established AIT comorbidity or elevation of anti-thyroid autoantibodies (ATA). Patients with isolated T1DM (ATA-negative) formed the second group. HLA-genotyping was performed by multiprimer PCR set for the three following genes: DRB1, DQA1 and DQВ1. Results. Prevalence of alleles DRB1*01, *03(017), *04, *07, *11 and genotypes 01/03, 01/04, 03/04 tends to be higher among patients with AIT comorbidity. The comorbidity group was also characterized by the trend towards higher prevalence of ?marker/marker? and ?marker/non-marker? combinations favouring the former variant. Conversely, ATA-negative patients exhibited trend for higher prevalence of ?non-marker/non-marker? combination. Conclusion. Statistically insignificant difference between HLA II alleles and genotypes in the two studied groups suggests that primary genetic factors are common in these two diseases. Plausibly, genes other than DRB1, DQA1 and DQВ1 determine the localization of the autoimmune process.

MODY is a heterogeneous group of diseases that stem from certain genetic mutations and are characterized by beta-cell dysfunction, early clinical onset (before the age of 25) and autosomal dominant inheritance. Nowadays many studies address atypical variants of diabetes mellitus (DM) and consequential problems in differential diagnosis. Though generally patients with MODY have normal body weight, the ongoing spread of obesity will probably produce comorbid forms and thus alter clinical picture. We present a case of DM in a 13-year-old patient that characterizes development of MODY3 in type 2 DM-like phenotype.

This study has demonstrated high sensitivity and specificity of the low-dose (5 mcg) 1-24-ACTH stimulation test used for diagnostics of the non-classical form of congenital adrenal hyperplasia (21-hydroxilase deficiency).

Aims. Search for the most pronounced HLA II markers of type 1 diabetes mellitus (T1DM) in Buryat ethnic group and analysis ofHLA-DQ trans-heterodimers. Materials and methods. Case control design was applied for assessment of 74 patients with T1DM and 61 healthy individuals. Alleleidentification was performed with multi-primer allele-specific PCR technique. Association of genetic markers with pathology wasevaluated according to odds ratio (OR) index. All calculations were performed with StatSoft and STATISTICA 6 software applications. Results. We show that regarding race-specific highly diabetogenic HLA class II haplotypes Buryat ethnic group holds intermediateposition between Mongoloids and Caucasians and none of those haplotypes are associated with T1DM. We revealed a statisticallysignificant association of T1DM with DQA1*0301+DQB1*0201+ phenotype represented by trans-coding alleles in 77% of cases. Onpopulation level DQA1*0301+DQB1*0302+ or *0201+ phenotype is found to be the most sensitive marker. It was registered in 43%of patients with T1DM against 11.5% of controls (OR 5.9; рс=0.0094). DQA1*0301+/DQВ1*0201 and DQВ1*0302 phenotype is themost specific marker, registered in 16% of patients, but not found in controls (OR 11.8; рс=0.047).Conclusions. HLA-mediated risk for development of T1DM in Buryat ethnic group is determined by HLA-DQ trans-heterodimers.

We have studied incidenceof immunological markers of celiac disease in children with diabetes mellitus type 1 (DM1) and their correlation with clinical peculiarities and polymorphous alleles of HLA. It was shown that incidence of celiac markers is higher in DM1 children than in general population and makes up 7.4%. Patients who were seropositive with celiac antigens had gastrointestinal symptoms and iron deficiency more often. The occurrence rate of other autoimmune disorders in seropositive patients was 24%, with high count of autoantibodies towards transglutaminase (AbTT) — 50%. More than 78% of seroposetive patients possessed haplotypes DQ2 and|or DQ8 HLA. The occurrence rate was identical. In patients with high AbTT occurrence of HLA genotypes with DQ2 and/or DQ8 rose up to 100%.

The paper is dedicated to clinical and laboratory aspects of Diabetes Mellitus non-immune forms, such as neonatal Diabetes Mellitus, Maturity Onset Diabetes of young (MODY), DIDMOAD-syndrome, Wolframe syndrome, Alstrom syndrome and its determinating genes. The analysis of proper clinical results are present in this paper.

Type 1 diabetes mellitus (DM1) is characterized by varying levels of morbidity in different populations and its overall increase in the majority of developed countries during the last 30 years. According to IDF, as many as 218,000 new cases of DM1 are registered annually all over the world of whom 75,800 (49%) are children at the age from 0 through 14 years. The yearly incremental increase of DM1 morbidity in this group is estimated at 3%. The marked ethnic variability of DM1 morbidity may be attributed to the different living conditions (environmental factors), population-related differences in the frequency of diabetes-predisposing and protective genetic markers, and the presence of specific markers in different populations. The population-based studies on the occurrence of molecular-genetic markers of DM1 in different ethnic groups confirmed the important role of genetic factors as predictors of diabetes and promoted the understanding of their contribution to the development of the disease in different ethnoses. The results of relevant original and published investigations are discussed.

Эффективным и доступным методом диагностики неклассической формы недостаточности фермента 21-гидроксилазы является стимуляционная проба с синтетическим аналогом адренокортикотропного гормона пролонгированного действия. Стимулированный уровень 17-ОР более 50 нмоль/л отражает нарушение ферментативной активности и в 80% случаев подтверждает наличие врожденной ферментопатии. Концентрация 17-ОР в пробе от 30 до 50 нмоль/л не может рассматриваться в качестве критерия диагностики неклассической формы заболевания, что определяет необходимость верификации диагноза методом молекулярно-генетического анализа с детекцией мутаций в гене CYP21 .