7 research outputs found

    C-peptide levels and the prevalence of islets autoantibodies in children with type 1 diabetes mellitus with different duration of the disease

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    BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the development of absolute insulin deficiency. In some patients residual insulin secretion may persist for a long time. C-peptide is a widely used to measure the pancreatic beta cells function, in clinical practice and in research studies.AIM: To assess C-peptide levels and presence of islets autoantibodies (Ab) in children with different duration of T1DM and to identify factors associated with the preserved secretion.MATERIALS AND METHODS: Single-center cross-sectional study including data from 703 cases of children with T1DM, examined in the Endocrinology Research Center in 2016-2020, who was underwent a study of C-peptide levels and was positive for one or more islets antibodies (ZnT8, IA-2, GAD, ICA, IAA). There were 3 groups of patients: 1st — T1DM duration < 1 year, 2nd — from 1 to 5 years, 3rd — > 5 years.RESULTS: The median of the fasting C-peptide level in the 1st group was 0.6 ng/ml [0.27; 1.09]; in the 2nd group — 0.2 ng/ml [0.01; 0.8]; in the 3rd group — 0.01 ng/ml [0.01; 0.037]. The preserved secretion of C-peptide (> 0.6 ng/ml) was determined in 51.4% in the 1st group, in 31.4% — in the 2nd group and in 11.4% in the 3rd group. In patients with obesity during the first year from the T1DM diagnosis C-peptide levels above 1.1 ng/ml was determined significantly more often (65.2%), as well as at the period of 1 to 5 years of the disease (35.7%), compared with children with normal BMI (18.5% and 14.5%, respectively) or overweight (15.7% and 19%, respectively), p <0.01. A negative correlation was found between C-peptide levels and the duration of T1DM (r = -0.489, p = 0.000), the daily dose of insulin (r = -0.637, p = 0.000), a positive association was found with the age of diagnosis of T1DM (r = 0.547, p = 0.000). The frequency of the presence of one type of islets autoantibodies in all groups was 29.5%, 2 types — 33.6%, 3 and more types — 36.9%. The titer of IA-2, ZnT8 decreased with the disease duration (p <0.05 and p <0.01, respectively), while the titer of ICA increased (p <0.01). No associations between the types, number, antibodies titer and C-peptide levels, age of disease manifestation were found.CONCLUSION: C-peptide levels in children with T1DM in groups with older age at diagnosis and with obesity is significantly higher for the first 5 years of the disease. The study have shown the titer of IA-2, ZnT8 is decreasing with the disease duration, in turn, the frequency of detection of ICA increases. No association between C-peptide levels and the type, number and titer of antibodies were found

    Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients

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    BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therap

    The role of specific pancreatic antibodies in the differential diagnosis of complete clinical and laboratory remission of type 1 diabetes mellitus and MODY in children

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    BACKGROUND: T1D is characterized by autoimmune destruction of pancreatic β-cells, which develops due to genetic and environmental risk factors. Shortly after initiating the treatment with insulin, 80% of children with T1D may require smaller doses of insulin and develop clinical and laboratory remission of the disease so called «honeymoon». The issue of whether there is a need of differential diagnosis between autoimmune DM and non-immune forms of DM raises in cases of preclinical diagnosis of T1D and laboratory remission for more than 6 months.AIM: To study the clinical, immunological, genetic characteristics of T1D remission phase and MODY in children, to determine the diagnostic criteria for T1D and MODY in children.MATERIALS AND METHODS: A single-centre, cross sectional noncontrolled comparative study of two independent cohorts. Data of 150 children examined in the Endocrinology Research Center (January 2016–June 2021). First cohort included patients with complete clinical and laboratory remission of T1D (n=36), second cohort included patients with MODY, confirmed by genetic study (n=114).RESULTS: The median age of diabetes manifestation was significantly higher in patients with T1D — 11.25 years [8.33; 13.78] than in patients with MODY — 7.5 years [4.6; 12.2] (p=0.004). In patients with T1D remission the level of glycated hemoglobin was 6.0% [5.6; 6.4], in group with MODY — 6.5% [6.2; 6.7] (p<0.001). Patients with monogenic diabetes had impaired fasting glucose — 6.27 mmol/l [5.38; 6.72], while patients with remission phase had normoglycemia — 5.12 mmol/l [4.17; 5.87]. The oral glucose tolerance test was perform to all patients, two-hour glucose level did not significantly differ in two groups (p=0.08). A strong family history of diabetes in patients with MODY registered more often (93% vs. 66.7%). A positive autoantibody titer detected more often in patients with remission of T1D (77.8%) than in patients with MODY (11.4%). In addition, no more than 1 type of autoantibodies was detected in patients with MODY.CONCLUSION: Antibodies ZnT8 and IA2 showed the greatest significance for the differential diagnosis of T1D and MODY in cases with long absents of insulin requirement in children with diabetes mellitus. Genetic test is recommended in seronegative cases. If only one type of AT is detected, specialist should decide on the need to do diagnostic genetic test based on a comprehensive analysis of the patient’s clinic characteristics, including family history, manifestation and blood glucose levels

    Полиморфные варианты протеасомных генов PSMA3 и PSMA6 у детей с суставным синдромом и ювенильным идиопатическим артритом

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    A comparative analysis of three single nucleotide variations of the proteasomal genes PSMA3 (rs2348071) and PSMA6 (rs2277460 and rs1048990) was carried out in the groups of children from 1 to 16 years old with the autoimmune rheumatic disease - juvenile idiopathic arthritis (JIA; n = 199), with articular syndrome of non-autoimmune etiology (n = 229) and in the clinical control group with neither autoimmune nor chronic inflammatory diseases (n = 379). PCR, PCR–RFLP and real-time PCR were used for genotyping. It was found that the CG genotype and G allele of rs10489990 polymorphism (OR = = 1.93; 95 % CI 1.29-2.90; p = 0.002 and OR = 1.51; 95 % CI 1.11-2.04; p = 0.008 respectively), as well as the AA genotype of rs2348071 polymorphism (OR = 1.89; 95 % CI 1.02–3.49; p = 0.044) are associated with the JIA susceptibility, but not with articular syndrome. The established JIA risk genotypes may indicate the involvement of PSMA3 and PSMA6 genes in the development of an autoimmune reaction. In combination with other risk DNA markers, they can be proposed to assess a genetic predisposition to JIA. It was also revealed that the frequencies of risk genotypes and alleles for JIA in the group of patients with articular syndrome as a whole occupy an intermediate position between JIA and control group frequencies. This may indicate an increased JIA risk in some patients with articular syndrome.Проведен сравнительный анализ частоты встречаемости полиморфных вариантов по трем локусам протеасомных генов PSMA3 (rs2348071) и PSMA6 (rs2277460 и rs1048990) в группах пациентов в возрасте от 1 до 16 лет с аутоиммунным ревматическим заболеванием ювенильным идиопатическим артритом (ЮИА; n = 199), с суставным синдромом при заболеваниях не аутоиммунной этиологии (n = 229) и в группе клинического контроля без аутоиммунных и хронических воспалительных заболеваний (n = 379). Для генотипирования использованы методы аллель-специфичной ПЦР, ПЦР–ПДРФ и ПЦР в реальном времени. Установлено, что генотип CG и аллель G полиморфизма rs10489990 (соответственно OR = 1,93; 95 % CI 1,29-2,90; p = 0,002 и OR = 1,51; 95 % CI 1,11-2,04; p = 0,008), а также генотип АА полиморфизма rs2348071 (OR = 1,89; 95 % CI 1,02–3,49; p = 0,044) ассоциированы с риском развития ЮИА, но не суставным синдромом. Установленные рисковые для ЮИА генотипы могут свидетельствовать о вовлеченности генов PSMA3 и PSMA6 в развитие аутоиммунной реакции, что в комплексе с другими рисковыми ДНК-маркерами может быть предложено для оценки генетической предрасположенности к ЮИА. Также выявлено, что частоты рисковых для ЮИА генотипов и аллелей в группе пациентов с суставным синдромом в целом занимают промежуточное положение между ЮИА и контролем, что может указывать на повышенный риск возникновения ЮИА у части пациентов с суставным синдромом

    Microbial structure of nitrogen utilizers in Populus nigra L. compost and vermicompost

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    Eisenia fetida worms affecting the amount of bacteria from four trophic groups i

    A glucokinase gene mutation in a young boy with diabetes mellitus, hyperinsulinemia, and insulin resistance

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    Andrey O Emelyanov,1 Elena Sechko,1 Ekaterina Koksharova,1 Igor Sklyanik,1 Tamara Kuraeva,1,2 Alexander Mayorov,1,2 Valentina Peterkova,1,2 Ivan Dedov1 1Endocrinology Research Centre, Moscow, Russian Federation; 2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Abstract: We report the case of a 12-year-old boy with a glucokinase (GCK) mutation, and diabetes with hyperinsulinemia and insulin resistance. For 4 years, the patient intermittently received insulin medications Actrapid HM and Protaphane HM (total dose 5 U/day), with glycated hemoglobin (HbA1c) levels of 6.6%–7.0%. After extensive screening the patient was found to carry a heterozygous mutation (p.E256K) in GCK (MIM #138079, reference sequence NM_000162.3). Insulin therapy was replaced by metformin at 1,700 mg/day. One year later, his HbA1c level was 6.9%, postprandial glycemia at 120 min of oral glucose tolerance test was 15.4 mmol/L, hyperinsulinemia had increased to 508.9 mU/L, homeostasis model assessment index was 114.2 and the Matsuda index was 0.15. Insulin resistance was confirmed by a hyperinsulinemic euglycemic clamp test – M-index was 2.85 mg/kg/min. This observation is a rare case of one of the clinical variants of diabetes, which should be taken into account by a vigilant endocrinologist due to the need for nonstandard diagnostic and therapeutic approaches. Keywords: case report, insulin resistance, diabetes mellitus, MODY2, chil
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