ЦЕЛЬ: оценить распространенность и предикторы развития хронической болезни почек (ХБП) и сер- дечно-сосудистой (СС) патологии у пациентов с длительным течением сахарного диабета 1 типа (СД1). МАТЕРИАЛЫ И МЕТОДЫ: в исследование включено 500 пациентов с длительностью СД1≥20 лет. Проведены клинико-лабораторные, антропометрические методы обследования, оценка распространен- ности ХБП и СС патологии. РЕЗУЛЬТАТЫ: средний возраст пациентов на момент включения в исследование составил 42 года (35;53; 22-83); средний возраст дебюта СД1=13 лет (8;20;1-50); средняя длительность СД1=28 лет (23;34; 21-57). У 63,2% пациентов имелась ХБП различных стадий: С1А2 - 14 (2,9%), С1А3 – 4 (0,9%), С2А2 – 23 (4,6%), С2А3 - 7 (1,4%), С3а – 47 (9,4%), С3б – 26 (5,2%), С4 – 58 (11,6%), С5 – 77 (15,4%), где 70 пациентов (14%) находились на заместительной почечной терапии гемодиализом; после трансплантации - 60 (12%). Из 500 пациентов у 87 (17,4%) пациентов - ишемическая болезнь сердца, 83 (16,6%) -хроническая сер- дечная недостаточность, 15 (3%) - аритмия, 298 (59,6%) - атеросклероз артерий нижних конечностей, 173 (34,6%) брахиоцефальных артерий, 11 (2,2%) почечных артерий, 34 (6,8%) перенесли инфаркт миокарда, 21 (4,2%) - острые нарушения мозгового кровообращения. Факторы, влиявшие на развитие ХБП: возраст пациента ≤ 25 лет: ОШ=7,53 (95%ДИ 2,18;26,0; p=0,001), 26–45 лет: ОШ=3,92 (95%ДИ 1,83;8,38; p<0,001) vs возраст пациента≥46 лет; длительность СД1=20 лет vs 21-30 лет ОШ=22,22 (95%ДИ 8,70;58,82; p<0,001) и vs >30 лет ОШ=45,46 (95%ДИ 7,52;71,43; p<0,001). Манифестация СД1 в 1996-2002 гг. снижала риск развития ХБП в 10,75 раз (95% ДИ 4,37; 27,03) vs мани- фестация СД ранее. Возраст дебюта СД1 6-17 лет повышал риск достижения терминальной ХБП (тХБП) и трансплантации vs возраст дебюта >18 лет: ОШ=2,4 (95% ДИ 1,22; 5,022; р=0,012). Наличие выраженной артериальной гипертензии (АГ) повышало риск прогрессирования до тХБП и трансплантации почки: ОШ=15,3 (95%ДИ 2,1;112,3; р=0,007). Факторы повышения риска развития СС патологии: систолическое артериальное давление>140 мм рт.ст. ОШ=3,5 (95%ДИ 2,2-5,6; p<0,001), гипертрофия левого желудочка ОШ 5,4 (95%ДИ 3,6-8,2; p<0,001), АГ ОШ=8,8 (95%ДИ 4,9-15,7; p<0,001), курение ОШ=2,1 (95%ДИ 1,3-3,1; p<0,001); рСКФ<60 мл/мин/1,73 м2 ОШ=7,1 (95%ДИ 3,6-8,4; p<0,001), рСКФ <30 мл/мин/1,73 м2 ОШ=8,7 (95%ДИ 2,8-8,4; p<0,001), рСКФ <15 мл/мин/1,73 м2 ОШ=14 (95%ДИ 6,3-31,3; p<0,001); альбуминурия разовой мочи более 20 мг/л ОШ=2,4 (95%ДИ 1,6-3,6; p<0,001), диализ ОШ=14,1 (95%ДИ 6,2-32,1; p<0,001), трансплан- тация почки ОШ=11,7 (95%ДИ 5,4-24,9; p<0,001). Мужской пол и ожирение не оказали значимого влияния на развитие СС патологии. ВЫВОДЫ: результаты исследования определили прогностические факторы развития и прогрессиро- вания почечной патологии у пациентов с длительным течением СД1 (более молодой возраст, длитель- ность заболевания не более 20 лет, возраст дебюта от 6 до 17 лет) с меньшим шансом ее развития у лиц с манифестацией СД1 после 1996-2002 гг. Снижение почечной функции, особенно развитие терминаль- ных стадий ХБП, существенно увеличивает риск СС патологии, превышая по значимости традиционные факторы риска

Public organization “Russian Association of Endocrinologists”. Clinical guidlines.

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.

Цель: оценить значимость остеопонтина (ОПН) в развитии поздних диабетических осложнений у больных с длительным течением сахарного диабета 1 типа (СД1). Материалы и методы: в исследование включено 79 пациентов с длительным течением СД1 (более 20 лет). Было проведено обследование пациентов, в рамках которого изучались антропометрические данные, общеклинические, биохимические показатели крови и мочи, оценивалась степень компенсации СД по уровню НвА1С, определялись показатели фосфорно-кальциевого обмена (кальций, фосфор, паратгормон, витамин Д, фактор роста фибробластов 23 (FGF 23)), маркеры эндотелиальной дисфункции (ассиметричный диметиларгинин (ADMA)) и сердечной недостаточности (предсердный натрийуретический протеин (NT pro-BNP)). Всем больным проводилось эхокардиографическое исследование, c расчетом индекса массы миокарды левого желудочка (ИММЛЖ), мультиспиральна компьютерна томография (МСКТ) сердца с определением индекса Агатстона, отражающего степень кальцификации коронарных артерий. Результаты: получены отрицательные корреляции между сывороточной концентрации ОПН и возрастом пациентов (r=-0,249; р˂0,05), ИМТ (r=-0,267; р˂0,05). Отмечено наличие положительной ассоциации ОПН с уровнем мочевой экскреции альбумина (r=0,427; р˂0,05), ИММЛЖ (r=0,257; р˂0,05), отражающего степень выраженности гипертрофии миокарда левого желудочка (ГЛЖ). Обнаружена взаимосвязь ОПН с маркером эндотелиальной дисфункции ADMA (r=0,290), способствующего развитию как кардиальной, так и почечной патологии у больных СД1. Выводы: определена вовлеченность ОПН в развитие кардиальной и почечной патологии у лиц с СД1, что указывает на его диагностическую значимость в оценке рисков развития поздних диабетических осложнений, а также при верификации уже сформировавшейся, специфичной для СД, органной патологии.

AIM:To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease.MATERIAL AND METHODS:Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-β, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification.RESULTS:The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=-0,320; p<0.05) and the magnitude of coronary artery calcification (CI: r=-0.308; p<0.05). GIP showed a differently directed effect on the proinflammatory factors: fibrinogen (r=-0.264; p<0.05), CRP (r=-0.626; p<0.05), and FGF-23 (r=-0.341; p<0.05).CONCLUSION:The investigation has demonstrated the nonglycemic effects of incretins that favorably affect the pathogenetic processes underlying the late complications of DM1. The findings point to the potential efficacy of incretin-based drugs in preventing and treating the late complications of DM, which necessitates the conduction of larger investigations.

AIM:To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA).MATERIAL:100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography.METHODS:All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen.RESULTS:Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression model identified diabetes, reduced renal function, previous myocardial infarction, smoking, ADMA and fibrinogen as factors associated with presence of multifocal atherosclerosis.CONCLUSION:Coexistence of atherosclerosis in two or more vascular beds was more frequent in P with diabetes and hemodynamically significant CA atherosclerosis than in PWD. It was associated with renal and cardiac dysfunction, excessive activation of mediators of inflammation, hemostasis, and factors of endothelial damage.

Aim. To study the prognostic value of multifocal atherosclerosis (MFA) in patients with diabetes mellitus (DM) at high risk for myocardial ischemia who need coronary angiography (CAG).Subjects and methods. The investigation included 148 patients: 25 with type 1 DM (DM1), 73 with type 2 DM (DM2), and 50 without DM who had undergone CAG. Duplex ultrasound scanning of lower limb vessels and brachiocephalic and renal arteries was carried out in all the patients.Results. Involvement of two or more vascular beds was noted in 60% of the patients with DM1, in 68.4% of those with DM2, and in 34% of those without DM (p < 0.05). Regression analysis showed that the risk factors of MFA were defined to be myocardial infarction (MI) in the history (OR=2.4; p=0.02), DM (OR=3.9; p=0.0002), smoking (OR=2.4; p=0.05), elevated creatinine (OR=6.5; p=0.002) and fibrinogen (OR=6.8, p=0.004) levels. Among the DM patients, there were 26.5% of those who had achieved a main assessment criterion (a combined end point (CEP)), such as death, urgent hospitalization for heart failure, nonfatal MI, nonfatal stroke, lower extremity amputation, double creatinine levels, and achievement of end-stage renal failure during a 24-month follow-up. In patients without carbohydrate metabolic disturbances, this indicator was 12% (p=0.01). During the prospective study, a total of 6.1% of patients died in the DM group; all the patients in the non-DM group completed the study. Calculation of survival rates by the Kaplan-Meier method indicated that the DM patients with concurrent atherosclerotic lesion had achieved CEP significantly more frequently than the comparison group. Such differences were absent among the persons without carbohydrate metabolic disturbances.Conclusion. The regression analysis has shown that prior MI, DM, smoking, creatinine and fibrinogen levels are factors associated with the development of MFA in the examined groups. In the patients with DM, concurrent atherosclerosis of two or more vascular beds is an important factor for the progression of cardiovascular and renal diseases.

During latest decade, as threat of acute complications of diabetes mellitus was surmounted, cardiovascular complications became leadingcause of death. Clinical manifestation of coronary, brachiocephalic and renal atherosclerosis is quite dramatic in diabetes mellitus,which determines extent of dissemination and intensity of lesions. Combination of these mutually confounding conditions is a characteristicproblem of patients with diabetes mellitus. Presence of 2+ risk factors (one of which is diabetes mellitus in itself) requiresactive examination in order to rule out coronary, brachiocephalic, peripheral and renal artery lesions. Aggressive care is necessaryin order to control progression of disease and administer adequate conservative and endovascular treatment with account of high riskof combination of lesions.

Current article presents data on effects of intensive glycemic control with Diabeton MR on development and progression of diabeticnephropathy in patients with type 2 diabetes mellitus (T2DM), accumulated from ADVANCE (Action in Diabetes and Vascular Disease:Preterax and DiamicroN Modified Release Controlled Evaluation study). Influence of intensive therapy with Diabeton MR wasassessed in that study separately and in conjunction with active antihypertensive treatment with perindopril and indapamide.

The dramatic increase in the number of patients with diabetes mellitus (DM) and chronic renal disease (CRD) in the recent years emphasizes the close association between the two conditions and the leading role of DM in the development of renal pathology. Diabetology and nephrology are highly costly branches of public health, and the burden of substitution renal therapy in DM patients continues to grow. The necessity of a renoprotection program at the early stages of DM for the prevention or delay of terminal renal insufficiency becomes increasingly clear. Such program should be based on the conceptual model of the evolvement of diabetic nephropathy as a consequence of combined action of metabolic and hemodynamic factors modulated by genetic ones.

Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I). Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.