Hypoglycemia in type 2 diabetes mellitus patients — cerebral, cognitive, psychosocial and clinical aspects

The review article describes modern approaches to hypoglycemia in diabetes mellitus (DM) patients, its clinical and laboratory diagnostics, and its current classification. Hypoglycemia has the highest impact on cardiovascular morbidity and mortality, including stroke. Cerebral damage in neuroglycopenia, as well as neurological aspects in this group of patients, are discussed. The authors describe glycopenia’s influence on cerebral metabolism, counter-regulatory response, and impaired hypoglycemia recognition, as well as modern neuroimaging techniques that may enhance differential diagnostics in complex cases. The epidemiology of neurocognitive disorders in DM patients and their association with hypoglycemic conditions is outlined, together with psychosocial aspects of its consequences — both for the patient and relatives and for the medical professionals. The search for ways to reduce the burden of hypoglycemia from the standpoint of an effective and safe strategy for treating patients with type 2 diabetes does not lose its relevance, and therefore data on the prevalence of hypoglycemic conditions of varying severity when using certain classes of hypoglycemic drugs are presented. A therapeutic approach that maximizes metabolic control while reducing hypoglycemia to a minimum may determine further possibilities for personalized DM management

Acute ischemic stroke in the setting of essential thrombocytemia (clinical cases)

This article describes several clinical cases of acute ischemic stroke among patients suffering from essential thrombocytemia. Ambiguity of etiological factors of stroke is demonstrated among patients with this pathology. Thrombocytosis and high allele load in the Jak2 gene play an important role (even with normal platelet count) in progression of cerebrovascular disease. Also the question of effectiveness of preventive and etiological therapy is considered

Формализованная оценка системной тромбогенности у пациентов с ишемическим инсультом, развившимся на фоне истинной полицитемии

Introduction. Thrombosis diagnosis and prevention in patients with Polycythemia vera (PV) suffered an ischemic stroke (IS) are still open. The aim was to find the reasons for systemic thrombogenicity and to compare the applicability of the main scales assessing thrombosis risk in patients with PV suffered IS.Materials and methods. We followed up 127 people (42-75 y.o.), of which 68 were patients with PV suffered IS (group I) and 59 non-PV-patients with ischemic stroke (group II). Clinical study included common blood analysis, rheological properties of erythrocytes, coagulation and endothelial parameters, cytokines, inflammation markers, angiogenesis markers, and testing for the V617F mutation in the JAK2 gene. The follow up included common and neurological examinations as well, and the assesment of thrombosis risk factors with both Caprini scale and CHA2DS2-VASc scale. All patients were examined twice as in the acute period of IS as well as in 16-18 months.Results. Between the groups no significant differences were found for the NIHSS average score and for Bartel index as well.The Caprini score belonged to the “very high risk” (score > 6) in both groups in the acute period of IS. At the same time, the score “8-10 points” prevailed in group II (68%) whereas the score “11-12 points” prevailed in group I.In the acute time of IS the CHA2DS2-VASc score revealed 12% of patients from both groups who had a score of “3-4 points” (moderate risk of thrombosis).In group I thrombotic complications rate correlated significantly with the JAK2V617F gene allelicloading (r = 0.236; p < 0.05), and the development of recurrence cerebrovascular disorders correlated significantly with Caprini score (r = 0.241; p < 0.05), but not with CHA2DS2-VASc score.Aiming to predict thrombotic complications in PV-patients the threshold (cut off) points were established for those markers as factor VIII, factor VII, red blood cell deformability, thrombin activated fibrinolysis inhibitor (TAFI), red blood cell count, white blood cell count, t-PA, VEGF-A, p-thrombomodulin, and ADAMTS-13.This pattern of parameters showed the odds ratio of thrombotic complications 10.3 (95% CI 7.6-13.8) in PV-patients in thelong-term period.At the end of the follow up the Caprini score showed a trend towards a decreasing in total while the CHA2DS2-VASc score remained virtually unchanged.Conclusion. We assume the accurate assessment of thrombotic risk in patients with Polycythemia vera suffered an ischemic stroke requires a proposed pattern of parameters including the test for JAK2V617F allelicloading and the calculation of Caprini score but not CHA2DS2-VASc score. Final results may provoke to change standard antithrombotic therapy in those patients towards its intensification due to pathogenetic featues of cancer-associated thrombosis.Цель. Целью нашего исследования было выявление причин системной тромбогенности и сравнительный анализ применимости основных шкал оценки степени риска развития тромбозов у пациентов с истинной полицитемией, перенесших ишемический инсульт.Материалы и методы. Обследовано 127 человек (возраст от 42 до 75 лет), из которых 68 пациентов перенесли ишемический инсульт (ИИ) на фоне ИП (I группа), и 59 пациентов перенесли ишемический инсульт, но не имели ИП (II группа). Клиниколабораторное обследование включало общий анализ крови, исследование реологических характеристик эритроцитов, исследование параметров системы гемостаза и функции эндотелия, определение цитокинов, маркеров воспаления активности ангиогенеза, а также количественное молекулярно-генетическое исследование мутации V617F в гене JAK2. Клиническое обследование включало общий и неврологический осмотры, уточнение клинических факторов риска, сбор анамнеза, а также оценку риска развития венозных тромбоэмболических осложнений (ВТЭО) по шкалам Caprini и CHA2DS2-VASc. Все пациенты были обследованы в острейшем периоде ИИ и спустя 16-18 мес.Результаты. При оценке неврологических симптомов в остром периоде ИИ в обеих группах средняя оценка по шкале NIHSS и по индексу Бартель статистически значимо не различались между группами. Оценка по шкале Caprini в остром периоде ИИ была в категории «очень высокий риск» (количество баллов > 6) у пациентов обеих групп. При этом во II группе преобладала оценка «8-10 баллов» (68%), тогда как в I группе больных преобладала оценка «11-12 баллов». Оценка по шкале CHA2DS2-VASc в остром периоде ИИ выявила в обеих группах по 12% пациентов с оценкой «3-4 балла» (умеренный риск тромбоза). В I группе частота тромботических осложнений достоверно коррелировала с величиной аллельной нагрузки гена JAK2V617F (r = 0,236; p < 0,05), а возникновение повторных нарушений мозгового кровообращения с количеством баллов по шкале Caprini (r = 0,241; p < 0,05), но не по шкале CHA2DS2-VASc. Проведение ROC-анализа для прогноза тромботических осложнений у пациентов I группы позволило установить пороговые значения наиболее информативных лабораторных маркеров: фактор VIII, фактор VII, деформируемость эритроцитов, активируемый тромбином ингибитор фибринолиза (TAFI), количество эритроцитов, количество лейкоцитов, концентрация t-PA, концентрация VEGF-А, концентрация p-тромбомодулина и концентрация ADAMTS-13. При использовании этой панели параметров отношение шансов возникновения тромботических осложнений в отдаленном периоде у пациентов I группы составило 10,3 раза (95% ДИ 7,6-13,8). В конце периода наблюдения установлено, что по шкале Caprini отмечена тенденция к общему снижению суммарного балла, тогда как оценка по шкале CHA2DS2-VASc практически не изменилась.Заключение. Учитывая роль ИП в формировании системной тромбогенности и, как следствие, в величине риска развития ВТЭО, для более точной характеристики групп риска уместно использовать шкалу Caprini, а также паттерн показателей, включающий величину аллельной нагрузки JAK2V617F и объединенную предиктивную панель лабораторных маркеров. Тем самым это может явиться обоснованием для изменения схем стандартной антитромботической терапии у таких больных в сторону ее усиления и с учетом особенностей патогенеза рак-ассоциированного тромбоза

Functional brain MRI in the setting of drug correction of obesity

AIMS. Study of the dynamics of brain activity using functional MRI (fMRI) in obese patients treated with sibutramine (Reduxine®).MATERIALS AND METHODS. The study enrolled patients with a body mass index (BMI) ≥30 kg/m2 . All participants underwent initial brain fMRI mapping. The obesity cohort was treated with sibutramine at a dose of 10 or 15 mg per day for 3 months. After treatment patients with obesity underwent a second fMRI mapping to assess changes against the initial mapping.RESULTS. The study included: 30 patients (86,7% women) with mean age of 31 [27.25; 36] years, mean body weight (BW)  - 106 [95.75; 121.75] kg, mean BMI 37.4 [33.55; 41.9] kg/m2 , mean waist circumference (WC) - 109 [100; 114.75] cm. The most marked activation volume (via fMRI) was observed in patients with obesity (before treatment) in the visual cortex (occipital lobes). After 3 months of treatment with sibutramine, 80% of patients lose ≥5% of BW. Mean BW decrease was -7.2 [-13.46; -5.37] kg, BMI decrease — -7.2 [-13.49; -5.34] кг/м2 , WC decrease — -6.9 [-11.88; -4.03] см, p <0,05. According to fMRI data, a  decrease in brain activation in the projection of the occipital lobes (35%), left insula (44%), and increase inactivation by 70% in the area of the left DMPF.CONCLUSION. A dynamic study of brain activity using fMRI in obese patients showed that during treatment with sibutramine, a decrease in body weight is accompanied by a decrease in activation in the projection of the occipital lobes and the left insular lobe of the brain, and an increase in activation in the area of the left DMPFC. These data may indicate a decrease in the emotional perception of high-calorie food, a decrease in motivation to eat it, and an increase in cognitive control. In general, the noted dynamics of the functional activity of the brain in obese patients against the background of obesity therapy can be regarded as a change in previously formed patterns of eating behavior

Unsolved Issues of Atherosclerosis Prevention and of Adequate Lipid-lowering Therapy in Patients with Acute Ischemic Cerebrovascular Accident

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7

Symptomatic and silent cerebral ischemia (detected on MRI) in patients with type 2 diabetes mellitus after carotid revascularization procedures

Background: Type 2 diabetes mellitus (T2DM) is a significant independent risk factor for ischaemic stroke. Carotid revascularisation procedures are an effective method of primary and secondary stroke prevention. However, patients developed postoperative acute ischaemic lesions (AILs), which were identified via magnetic resonance imaging (MRI) of the brains. Most of the patients with these AILs lack clinically overt symptoms. Aims: To assess the risk of ischaemic brain damage in patients with T2DM in the setting of carotid angioplasty with stenting (CAS) or carotid endarterectomy (CAE). Materials and methods: This open prospective study comprised of 164 patients with carotid atherosclerosis, who have undergone either CAS or CAE. Patients with T2DM were included in Group 1: 38 patients and 28 patients with CAE. Group 2 included patients without T2DM: 62 patients with CAS and 36 patients with CAE. All patients underwent a thorough neurological examination and diffusion-weighted brain MRI. In patients with T2DM, plasma glucose levels and glycated haemoglobin (HbA1c) were determined and their relationships to brain damage were evaluated. Results: In CAS, there were no statistically significant differences in the AIL frequency in patients with and without T2DM. AILs were found in 15 patients with T2DM (39.8%) and 29 patients without T2DM (46.8%, р = 0.24); three patients without T2DM were diagnosed with stroke. Of the 28 patients with T2DM who underwent CAE, 13 had AIL (46.4%); three had stroke (10.7%). In patients without T2DM, AILs were less prevalent in seven cases (19.4%, р = 0.012) and appeared asymptomatic. Following CAS, the baseline HbA1c levels were higher in patients with T2DM who developed AILs compared to those who did not develop AIL, 7.8% ± 1.4% vs 7.1 ± 1.1% (р = 0.0469). Negative impact of hyperglycaemia on the risk of cerebral ischaemia was observed in patients who underwent CAE, the baseline fasting plasma glucose level was 8.5 ± 1.9 mmol/l vs 7.0 ± 1.5 mmol/l in patients without AIL (р = 0.014). The baseline HbA1c levels in patients with and without AILs were 8.0% ± 1.7% and 6.9% ± 0.9% respectively (р = 0.023). Conclusions: Carotid revascularisation procedure for patients with carotid atherosclerosis may be associated with risk of stroke and asymptomatic acute cerebral ischaemic lesions, which are more prevalent in patients with T2DM. Also, increased HbA1c levels is a risk factor for AIL