Aim. To study the quantity of endothelial progenitor cells (EPCs) and levels of vascular endothelial growth factor A (VEGF-A) in patients with type 2 diabetes mellitus (T2DM) after endovascular interventions on coronary and peripheral arteries.Materials and methods. We observed 68 patients with stable angina pectoris and critical limb ischaemia, admitted for elective percutaneous coronary intervention and endovascular revascularisation of the lower extremity. The number of CD34+ VEGFR2+ CD45-and CD34+ CD133+ CD45-cells and levels of VEGF-A were determined before endovascular intervention and 2-4 days after the surgery.Results. We found that in patients without diabetes, the levels of EPCs increased significantly after endovascular interventions (CD34+ VEGFR2+ CD45-cells, p < 0.0001; CD34+ CD133+ CD45-cells p = 0.041). The levels of EPCs in the peripheral blood of patients with T2DM before and after endovascular interventions did not significantly differ. The analysis of VEGF-A showed a statistically significant increase after intervention in both groups. In addition, in patients with an HbA(1c) level of < 8% and duration of diabetes of < 10 years, the levels of EPCs significantly increased (p = 0.001 and 0.005, respectively). In patients with an HbA(1c) level of >= 8% and duration of diabetes of > 10 years, the levels of EPCs before and after endovascular interventions did not significantly differ.Conclusions. Patients with diabetes exhibited impaired EPC mobilisation after endovascular interventions. Poor glycaemic control and a long duration of diabetes are among the risk factors of EPC mobilisation.
Nenets are Samoyedic people belonging to Ural contact minor race, with combined anthropological signs of both Caucasoid and Mongoloid races. In this population, the occurrences of type 1 diabetes mellitus (T1DM) were registered during 30 years. Aim . The study aimed to investigate the incidence of human leucocyte antigen (HLA)-haplotypes in Nenets compared with those in the Russian population. Materials and Methods . HLA-typing was performed in 61 healthy Nenets subjects residing in the Arkhangelsk district, 341 Russian subjects from Moscow and natives from the Vologda district. Results . DRB1*04-DQA1*0301-DQB1*0302 was similar in all the three study populations: 11.5%, 8.5% and 11.6% for Nenets, Moscow and Vologda populations, respectively (p > 0.05). However, the incidence of the second most important high predisposed haplotype DRB1*17(03)-DQA1*0501-DQB1*0202 was significantly lower in Nenets (1.6%) than in the Moscow and Vologda populations (10% and 7.4%, respectively) [(p1.2 = 0.03 (x2 = 4.42); p1.3 = 0.12 (x2 = 2.46)]. The incidence of DRВ1*01-DQA1*0101-DQB1*0501 haplotype specific for both Russian populations was also significantly lower in Nenets (3.3%) than in the Moscow and Vologda populations (11% and 12.4%, respectively) [(p1.2 < 0.05 (x2 = 3.34); p1.3 < 0.05 (x2 = 3.85)]. The incidence of protected haplotypes (DRB1*11-DQA1*0501-DQB1*0301 and DRB1*13-DQA1*0102-DQB1*0602/8/DRB1*13-DQA1*0103-DQB1*0602) was significantly higher in Nenets than in the Moscow and Vologda populations: 32.8% versus 12.5% and 9.1%, respectively [(p1.2 < 0.001 (x2 = 13.48); p1.3 < 0.001 (x2 = 17.3)] and 16.4% versus 8.5% and 11.1%, respectively [(p1.2 = 0.07 (x2 = 3.14); p1.3 = 0.3 (x2 = 0.97)]. The incidence of some neutral haplotypes was also significantly higher in Nenets: haplotype DRB1*12-DQA1*0501-DQB1*0301 was detected in 29.5% of Nenets compared with 2.5% and 1.2% of the Moscow and Vologda populations, respectively [(p1.2 < 0.001 (x2 = 42.43); p1.3 < 0.001 (x2 = 37.66)]; haplotype DRB1*09-DQA1*0301-DQB1*0303 was detected in 14.8% of Nenets compared with 1% and 2.5% of the Moscow and Vologda populations, respectively [(p1.2 < 0.001 (x2 = 21.9); p1.3 < 0.001 (x2 = 10.04)]. Conclusions . According to preliminary evidence, the incidence of predisposed haplotypes was significantly lower and that of protected haplotypes was significantly higher in Nenets than in the Moscow and Vologda populations, which probably play a role in the very low incidence of T1DM in Nenets.
Aim — to research molecular genetic and clinical characteristics of diabetes mellitus MODY2 and MODY3 in children.Material and methods. Genetic testing for GCK and HNF1α was performed in 169 patients with carbohydrate metabolism disorders, with age of diagnosis under 18. Carbohydrate metabolism disorders were interpreted as MODY. Analysis of clinical data at the presentation of carbohydrate metabolism disorder and cases follow-up was provided in 62 patients with genetic confirmed MODY2 and 18 patients with genetic confirmed MODY3.Results. Ratio MODY2 and MODY3 was 3,4:1. Carbohydrate metabolism disorders were diagnosed earlier in MODY2 than in MODY3 — 7,8 years (4,0; 10,5) vs. 11,8 years (9,7; 13,5) (p<0,01). Degree of carbohydrate metabolism disorder was less in MODY2 — in 22,4% of patients all makers of carbohydrate metabolism disorder (HbA1c, fasting glycaemia, 120 min glycaemia) were less than diabetic range, in MODY3 all these makers were diabetics in 100% of cases. Patients with MODY2 significantly less frequently were treated with antihyperglycemic drugs. Carbohydrate metabolism disorders in one of the parents were diagnosed earlier in MODY3 — in 24 years (18,5; 35,3) vs. 32 years (27; 37) in MODY2 (p<0,05), parents were treated with antihyperglycemic drugs — in 94,4% vs. 22,2% respectively (p<0,01).Conclusion. This study is the largest in Russia and estimated that MODY2 is the most prevalence and has had milder presentation and less dysfunction of β-cells to compare to MODY-HNF1α.
Цель. Определить в выборках больных латентным аутоиммунным диабетом взрослых (LADA) и здоровых индивидов частоты аллелей и генотипов полиморфного маркера rs7903146 гена TCF7L2. Провести сравнительный анализ распределения аллелей и генотипов, изучить ассоциацию с развитием болезни. Материалы и методы. Обследовано 96 пациентов (46 женщин и 50 мужчин) с LADA-диабетом и 201 человек из группы контроля. Проведено количественное определение аутоантител GADA, ICA, IA-2A и ZnT8 в сыворотке крови пациентов LADA. Всем испытуемым провели типирование rs7903146 гена TCF7L2. Результаты. При сравнении частот аллелей и генотипов rs7903146 гена TCF7L2 обнаружено увеличение частоты Т аллеля и генотипа Т+ у пациентов с LADA-диабетом с низкими концентрациями аутоантител по сравнению с группой пациентов с высокими концентрациями и с контролем. Установлена ассоциация аллеля Т и генотипа Т+ с LADA-диабетом с низкими концентрациями аутоантител (р=0,02; OR=1,85; CI (95%)=1,10–3,13 и р=0,04; OR=2,14; CI (95%)=1,01–4,53 для аллеля Т и генотипа Т+). Заключение. Результаты исследования позволяют предполагать, что пациенты с LADA с низкими концентрациями аутоантител имеют генетически обусловленное сходство с СД2.
Patients with diabetes mellitus (DM) have a 2to 4-times higher risk of developing cardiovascular complications compared with non-diabetic controls. Hyperglycemia activates pathophysiological mechanisms that damage the endothelium. According to the current views, circulating progenitor cells derived from bone marrow repair the damage. These cells, known as endothelial progenitor cells (EPCs), maintain endothelial homeostasis and contribute to the formation of new vessels. Many clinical studies have reported that EPC population is dysfunctional and declines in numbers in patients with type 1 and type 2 DM. In addition, bone marrow doesn’t respond adequately to mobilizing stimuli in DM. Therefore, EPC alterations might have a pathogenic role in the complications of DM. In this review, EPC alterations will be examined in the context of macrovascular and microvascular complications of DM, highlighting their roles and functions in the progression of the disease.
Цель. Определение частоты встречаемости аутоантител, характерных для аутоиммунных панкреатитов и гастритов у пациентов с сахарным диабетом 1 типа (СД1), особенности клинической картины у пациентов, положительных по данным параметрам. Материалы и методы. Обследовано 84 пациента (39 мужчин, 45 женщин) с СД1, которые были разделены на две группы. Проведено биохимическое, иммунологическое и инструментальное обследование. Результаты. Выявлена высокая частота встречаемости маркеров аутоиммунных заболеваний желудочно-кишечного тракта у пациентов с СД1, а также установлена высокая частота встречаемости исследуемых антител у пациентов с отсутствием клинической симптоматики, признаков поражения по данным инструментальных методов диагностики. Заключение. На основе полученных данных можно предположить, что пациенты с СД1 имеют более высокий риск возникновения сопутствующих аутоиммунных заболеваний с возможностью их бессимптомного течения.
Цель. Поиск наиболее выраженных HLA класса II маркеров сахарного диабета 1 типа (СД1) в бурятской этническойгруппе, анализ роли транс-кодируемых HLA-DQ гетеродимеров. Материалы и методы. Методом случай-контроль обследовано 74 больных СД1 и 61 здоровый пациент. Идентификациюаллелей генов проводили методом мультипраймерной аллель-специфической ПЦР. Ассоциация признака с заболеваниемопределялась величиной показателя соотношения шансов (OR). Расчеты выполняли при помощи компьютерных программStatSoft STATISTICA 6. Результаты. Показано, что по частотам высокодиабетогенных расо-специфичных HLA класса II гаплотипов бурятскаяэтническая группа занимает промежуточное положение между монголоидами и европеоидами, и ни один из этих гаплоти-пов не ассоциирован с СД1. Выявлена статистически значимая ассоциация СД1 с фенотипом DQA1*0301+DQB1*0201+.В 77% случаев этот фенотип представлен транс-кодируемыми аллелями. На популяционном уровне наиболее чувствитель-ным маркером заболевания является фенотип DQA1*0301+DQB1*0302+ или/и *0201+. Он обнаружен у 43% больных про-тив 11,5% в контрольной группе (OR=5,9; рс=0,0094). Наиболее специфичным маркером является фенотип DQA1*0301+/DQВ1*0201 и DQВ1*0302. Он обнаружен у 16% больных против 0% в контрольной группе (OR=11,8; рс=0,047). Заключение. HLA-опосредованный риск возникновения СД1 в бурятской этнической группе детерминируется транс-кодируемыми DQ гетеродимерами.
Materials and methods. HLA genotyping was accomplished in 51 DM1 patients and 51 volunteers randomly selected from the indigenous population of Yakutia (Yakuts in three successive generations). Another 205 DM1 patients and 300 healthy subjects comprised random samples of patients and controls respectively from residents of Moscow and Moscow region. Results. HLA DRB1*17(03) allele proved to be the strongest one predisposing to DM1 in the Yakutian population (relative risk, RR=8,47) and DQB1*0304 in the Moscow population (RR=8,94). The presence of DRB1*04, DRB1*17(03), DQA1*0301, DQB1*0201, and DQB1*0302 accounted for RR >2 in both populations. Only two alleles, DRB1*04 and DRB17(03), in the Yakutian population and five of the six (DRB1*04, DRB1*17(03), DQA1*(0301), DQB1*0302, and DQB1*0304) in the Moscow one were closely associated with DM1 (RR >4). DRB1*09, DRB1*11, DQB1*13, DQB1*0602/8 in Yakutian and DRB1*11, DRB1*13, DQA1*0103, DQB1*0301, DQB1*0602/8 in Moscow populations had the highest protective potential (RR