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

MicroRNA detection in carotid atherosclerosis: prospects for clinical use

Carotid atherosclerosis is a significant cause of cerebrovascular disease. However, with many candidate markers, precise assessment of its development and progression risks is still limited. This paper reviews state-of-the-art concepts of microRNA as an atherogenesis biomarker throughout various stages including endothelial dysfunction, cholesterol/lipid metabolism, inflammation, oxidative stress, angiogenesis regulation, and proliferation and migration of vascular smooth muscle cells. Based on the available literature, we have described most significant microRNAs for each stage characterized in brief. We have visualized interactions between microRNAs and validated target genes with MIENTURNET and suggest and justify a set of microRNAs for further pilot studies of carotid atherosclerosis

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

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

Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity. Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease. Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers. Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient. In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile. Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis