I I Dedov

Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis

Screening using the Fracture Risk Assessment Tool (FRAX) is recommended in all postmenopausal woman and mеn over 50 (A1) in order to identify individuals with high probability of fractures. It is recommended to diagnose osteoporosis and start treatment in patients with fragility fracture of large bones of the skeleton and/or high individual probability of major fragility fractures (FRAX) and/or detected decrease in bone mineral density (BMD) up to –2.5 T-score as assessed by DXA in the femoral neck and/or lumbar vertebrae (A1). Patients with back pain, lifetime height loss of 4 cm or height loss of 2 cm since a previous medical examination, those who receive glucocorticoids, patients with long lasting decompensated type 2 diabetes mellitus, or those receiving insulin therapy, as well as patients who were previously diagnosed with fragility fractures at the other sites are advised to underwent standard lateral X-ray imaging of the spine (Th4—L5) in order to verify the presence of compression vertebral fractures (B1). Dual-energy X-ray absorptiometry (DXA) is recommended for individuals whose 10-year probability of major osteoporotic fracture (FRAX) falls within the medium risk group (B1). It is recommended to include the trabecular bone score (TBS) the FRAX algorithm in order to improve the sensitivity of this method (B1). Laboratory testing is recommended for the differential diagnosis with other causes of increased skeletal fragility in all patients with newly diagnosed osteoporosis and when previously prescribed antiosteoporostic treatment was ineffective (B1). Bisphosphonates (BPs), antibodies to receptor activator of nuclear factor kappa-beta ligand (RANKL) (denosumab), or parathyroid hormone analogue (teriparatide) are equally recommended to prevent fragility fractures and increase BMD in patients with osteoporosis (A1). Denosumab is also recommended to prevent BMD loss and fractures in females receiving aromatase inhibitors therapy for breast cancer and males with prostate cancer receiving hormone-deprivation therapy and having no bone metastases (A1). Since teriparatide has the anabolic effect, it is recommended as the first line treatment in patients with severe osteoporosis having history of vertebral fractures, in the individuals with very high risk of fragility fractures, or in the cases when antiresorptive treatment was ineffective (B1). All medications for treatment of osteoporosis are recommended in combination with calcium and vitamin D supplements (A1).

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus

AIMnThe purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM).nnnMATERIALS AND METHODSnThe study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA).nnnRESULTSnWe observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy.nnnCONCLUSIONnChanges in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

A 20-year prospective follow-up study to evaluate the development of retinopathy and nephropathy after the onset of type 1 diabetes mellitus: Contribution of glycemic control and metabolic memory

AIMnTo assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN).nnnSUBJECTS AND METHODSnA total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study.nnnRESULTSnDuring the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria.nnnCONCLUSIONnThe 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

Isolated left ventricular diastolic dysfunction in diabetes mellitus: opinions change

Aim — to compare the features of diastolic dysfunction (DD) with preserved left ventricular (LV) ejection fraction (EF) in patients with diabetes mellitus type 2 (DM2) with arterial hypertension (AH) and in patients with essential hypertension (EH) without diabetes. Material and methods . The study involved 87 patients with DD with preserved LV EF: 53 patients with DM2 with AH and 34 patients EH without diabetes. Transthoracic echocardiography was performed by ultrasonic imaging system iE33 xMATRIX («Philips», USA). DD was determined in a complex: type on the basis of the ratio parameters of pulsed-wave (E/A) and tissue ( e/a ) Doppler; and severity on the Е/ e values and pulmonary capillary wedge pressure (PCWP). Myocardial contractile function was assessed by traditional LVEF by Simpson and more exactly, in details on the basis of the longitudinal, radial and circular deformation of the LV myocardium by speckle-tracking echocardiography (using the program Q-lab 3.0 Advanced Ultrasound Quantification software). Results . The groups were comparable in clinical characteristics. The average level of HbA1c in patients with DM2 was 8.2±1.7%. The average LV EF by Simpson in the EH group was 59.9±8.1, in DM2 — 58.3±6.7 ( p =0.228). There were more severe disorders of LV Diastolic function in DM2 patients: the values of E/e ( p =0.000) and PCWP ( p =0.001) were significantly higher in diabetic patients (14,1±5,5 and 15,3±4,7 mm Hg) than in EH (9.7±2.3 and 11.9±1.3 mm Hg). Although that the LV EF (by traditional echocardiographic method of Simpson) was preserved in both groups , the LV global longitudinal strain (12.4±3.0) was significantly lower in DM2 ( p =0.005), than patients with EH (16.6±2.0) by speckle-tracking echocardiography. Conclusion . Severity of LV DD are harder in Patients with diabetes and hypertension, than in patients with EH with the similarity of clinical manifestations and data of traditional echocardiographic methods. There were found initial disorders of LV longitudinal myocardial fibers contraction by speckle-tracking echocardiography in patients with DM and preserved LV EF. The combination of impairment of systolic and diastolic function in diabetes is inseparable. Early development of combined systolic and diastolic dysfunction in DM2 is associated with a poor prognosis: a higher risk of early development of atrial fibrillation, ventricular arrhythmias and progressive heart failure.

Assuring epidemiological safety for healthcare of patients with diabetes mellitus

Healthcare associated infections (HAI) — infections that patients develop during the course of receiving healthcare in hospitals, outpatient department and at home, out of healthcare facilities, and infection resulting from occupational exposure. Patients with diabetes are vulnerablexa0to HAI. Infections increase metabolism problems in patients with diabetes; and vice versa, highxa0blood glucose level increases risk of infections. For assuring epidemiological safety for patients with diabetes infection control must be provided for the following medical practices: insulin injections; blood glucose test; care of diabetes foot; intravascular catheterization and surgery. Any invasive procedures increase the HAI risk. HAI are most commonly transferred through direct and indirect contact with the infection. Some of the main HIA preventive practices: staff cleaning hands with alcohol based sanitizer, single use of medical gloves, single use of insulin needles and syringes. In health facilities only multiple users and multiple blood glucose monitoring devices must be used by health providers. The protocol of glucose blood testing should include detailed disinfection procedures and additional measures to decrease the risk of potentially transmitting disease between patients and between patients and providers. Health providers should have special skills to care of patients with diabetes foot to perform non-traumatic procedures and infections control practices. Proper hand hygiene and gloves use combined with effective aseptic technique before catheter insertion and maintenance protect against severe HAI. Risk of infections significantly decreases when single-dose antibiotic was used before surgery as antimicrobial prophylaxis. To disease risk of infections patients should be recommended to strictly control diabetes during the weeks before elective surgical procedures.

Pharmacoeconomic analysis of conservative strategy for the treatment of patients with diabetic foot syndrome in Moscow

Aim. To perform cost-effectiveness analysis of prescription of pharmaceutical products and dressing materials and their consumption volume for inandout-patient treatment of diabetic foot syndrome (DFS). To analyse efficacy of the treatment in terms of modern therapeutic standards. Materials and methods. This retrospective study is based on the medical documentation of 139 DM1 and DM2 patients with DFS from differentmedical facilities of Moscow (2007). 72 patients were given general out-patient care by surgeons of city polyclinics, 50 ones received specialized aidin the regional Diabetic Foot Cabinet. 67 patients were hospitalized: 20 for general care in the department of purulent surgery of a military hospital,27 for specialized care in the department of purulent surgery of a city hospital, 20 for high-technology care in the endocrinological clinic of the FirstMoscow State Medical University. Results. Therapeutic strategy for DFS patients used in the regional Diabetic Foot Cabinet met the current therapeutic standards. General out-patientcare by surgeons of city polyclinics was at variance with the algorithms adopted in this country. Pharmacoeconomic analysis of the spectrum of pharmaceuticalproducts used for in- and out-patient treatment of DFS patients revealed frequent and ungrounded application of drugs whose woundhealing effect remains to be confirmed (pentoxifylline, thioctoic and alpha-lipoic acids). Conclusion. Additional training courses for surgeons of Moscow polyclinics are needed to improve the quality of medical aid to DFS patients. Suchpatients must be referred to regional Diabetic Foot Cabinets. Pentoxifylline, thioctoic and alpha-lipoic acids need to be substituted by pharmaceuticalswith validated therapeutic efficacy.

Giperprolaktinemiya. Sovremennye podkhody i starye problemy

Со времени выхода статьи E. Fluckiger и H.R. Wagner, посвященной влиянию алкалоидов спорыньи на фертильность и лактацию, прошло 40 лет [1]. Эта публикация открыла новую эру в эндокринологии. Особенностью гиперпролактинемии, отличающей ее от других эндокринных заболеваний явилось то, что данные о возможности лечения больных с гиперпролактинемией были получены раньше, чем был выделен сам гормон пролактин (ПРЛ) человека, и изучены основы этиологии и патогенезе гиперпролактинемического гипогонадизма (ГГ).К настоящему времени первые пациентки с гиперпролактинемией, получавшие терапию бромокриптином, давно стали бабушками. Уже пожелтели страницы первых статей посвященных лечению аденом гипофиза и исходам беременностей на фоне терапии алкалоидами спорыньи. Однако, согласно законам развития любой науки, в том числе медицины, происходит постепенное накопление данных по каждой изучаемой проблеме. И количество работ, посвященных ГГ, также продолжает увеличиваться с каждым годом. в настоящее время, по данным базы PubMed, число ссылок на запрос «prolactin» достигает 44 тыс., а ссылок«hyperprolactinemia» — более 5 тыс.Ключевыми документами, призванными облегчить и оптимизировать работу практикующих врачей, являются клинические рекомендации по тем или иным проблемам и заболеваниям. Однако, несмотря на то, что в нашей стране накоплен значительный опыт лечения гиперпролактинемии, рекомендации по ведению пациентов с данным заболеванием отсутствуют. Мы надеемся, что в ближайшее время они будут созданы. Но, вначале, представляется важным рассмотреть уже существующие в мире рекомендации по лечению больных с ГГ. в основу данной статьи положены две объемные работы, посвященные лечению пролактином и мониторингу ятрогенной гиперпролактинемии при проведении психотропной терапии [2, 3]. Одним из существенных недостатков этих работ является отсутствие указаний на уровень доказательности приводимых данных. При несомненной компетентности и актуальности указанных публикаций мы постарались критически рассмотреть представленную в них информацию.

Endokrinnaya khirurgiya: «Uzkaya» spetsial'nost' ili nasushchnaya neobkhodimost'?

Прошло несколько десятилетий с момента выделения из общей хирургии и утверждения в реестре медицинских специальностей кардиохирургии, нейрохирургии как самостоятельных дисциплин. Сейчас это покажется странным, но в свое время острые споры вызывало отделение от хирургии таких специальностей, как урология и оториноларингология. Необходимость организации специализированных хирургических служб в те уже далекие времена аргументировалась следующим: • огромным количеством больных, нуждающихся в специализированной помощи, появлением большого числа специалистов; • отсутствием и несоблюдением отраслевых стандартов лечения хирургами, выполняющими эти операции время от времени; • невозможностью осуществить статистический учет больных и объективно оценить результаты лечения; • стагнацией развития науки в этих областях. С нашей точки зрения, наступило время для того, чтобы рассмотреть через призму вышеперечисленных проблем необходимость организации службы эндокринной хирургии в России.

Strategiya poiska markerov geneticheskoy predraspolozhennosti k sosudistym oslozhneniyam sakharnogo diabeta na primere diabeticheskoy nefropatii

Актуальность. Сосудистые осложнения сахарного диабета, как и основное заболевание, являются клинически гетерогенными и этиологически многофакторыми патологиями, развитие которых находится под полигенным контролем. К клинической манифестации ангиопатий приводит сочетание нескольких факторов: гормонально-метаболических, генетических, экологических, а также ментальных и социально-поведенческих. Возрос интерес к участию генетических факторов в развитии диабетической нефропатии . Цель. Изучение генетической предрасположенности к патологии с использованием полиморфных маркеров различных генов-кандидатов с целью проверки предположения о том, что наличие маркера связано с ранним развитием и/или быстрым прогрессированием диабетической нефропатии. Материалы и методы. Наблюдали 45 больных, которые были разделены на 2 подгруппы: с наличием (п=14) и отсутствием ДН (п=31). Для оценки текущего контроля гликемии как метаболического фактора риска ДН у всех больных с помощью ионообменной хроматографии определяли уровень неферментативно гликированного гемоглобина. Концентрацию альбумина в моче исследовали нефелометрическим методом. Амплификацию поли морфных участков генов АСЕ и CAT определяли с помощью полимеразной цепной реакции (ПЦР) и проводился аллельный анализ. Сравнение частоты встречаемости аллелей и генотипов гена АСЕ и CAT в различных группах обследованных проводили с использованием точного критерия Фишера. Статистически значимыми считали различия при р>0.05. Достоверные различия частоты встречаемости генотипов II и DD гена АСЕ в группах случай (ДН+) и контроль (ДН-) свидетельствуют об ассоциации этого полиморфного маркера с диабетической нефропатией у больных ИЗСД. Результаты. В этиологии диабетической нефропатии существуют генетические факторы риска, один из которых в московской популяции больных ПЗСД четко идентифицирован как полиморфизм гена ангнотензпн-1-превращающего фермента. Другим модулятором генетической предрасположенности или устойчивости к ДН при ИЗСД может быть ген каталазы и его полиморфный маркер. Выводы. Опыт изучения ассоциации полиморфных маркеров различных генов-кандидатов с диабетическими ангиопатиями на примере ДН показал важность четкого определения фенотипов патологии и ее отсутствия.