New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes-Beyond and within GLP-1 Receptor Agonists.

Guidelines for the management of obesity and type 2 diabetes (T2DM) emphasize the importance of lifestyle changes, including a reduced-calorie diet and increased physical activity. However, for many people, these changes can be difficult to maintain over the long term. Medication options are already available to treat obesity, which can help reduce appetite and/or reduce caloric intake. Incretin-based peptides exert their effect through G-protein-coupled receptors, the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and glucagon peptide hormones are important regulators of insulin secretion and energy metabolism. Understanding the role of intercellular signaling pathways and inflammatory processes is essential for the development of effective pharmacological agents in obesity. GLP-1 receptor agonists have been successfully used, but it is assumed that their effectiveness may be limited by desensitization and downregulation of the target receptor. A growing number of new agents acting on incretin hormones are becoming available for everyday clinical practice, including oral GLP-1 receptor agonists, the dual GLP-1/GIP receptor agonist tirzepatide, and other dual and triple GLP-1/GIP/glucagon receptor agonists, which may show further significant therapeutic potential. This narrative review summarizes the therapeutic effects of different incretin hormones and presents future prospects in the treatment of T2DM and obesity.

Assessment of Hypertensive Patients' Complex Metabolic Status Using Data Mining Methods.

Cardiovascular diseases are among the leading causes of mortality worldwide. Hypertension is a preventable risk factor leading to major cardiovascular events. We have not found a comprehensive study investigating Central and Eastern European hypertensive patients' complex metabolic status. Therefore, our goal was to calculate the prevalence of hypertension and associated metabolic abnormalities using data-mining methods in our region. We assessed the data of adults who visited the University of Debrecen Clinical Center's hospital (n = 937,249). The study encompassed data from a period of 20 years (2001-2021). We detected 292,561 hypertensive patients. The calculated prevalence of hypertension was altogether 32.2%. Markedly higher body mass index values were found in hypertensive patients as compared to non-hypertensives. Significantly higher triglyceride and lower HDL-C levels were found in adults from 18 to 80 years old. Furthermore, significantly higher serum glucose and uric acid levels were measured in hypertensive subjects. Our study confirms that the calculated prevalence of hypertension is akin to international findings and highlights the extensive association of metabolic alterations. These findings emphasize the role of early recognition and immediate treatment of cardiometabolic abnormalities to improve the quality of life and life expectancy of hypertensive patients.

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.

Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus.

BACKGROUND: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage. PATIENTS AND METHODS: 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography. RESULTS: We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix. CONCLUSIONS: Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE.

Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies.

Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. All patients demonstrated undetectable baseline anti-SARS-CoV-2 immunoglobulin levels before CP. Each patient received at least a complete course of remdesivir and at least one unit of CP. Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of B-cell lymphopenia (p = 0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p = 0.017), length of hospital stay (p = 0.007), and PCR positivity (p = 0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p < 0.001) and hospital stay (p < 0.0001). In those cases where there were at least 10 days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p = 0.006). In conclusion, the combination of inhibition of viral replication with passive immunization was proved to be efficient and safe. Our results suggest the clear benefit of early, combined administration of remdesivir and CP to avoid protracted COVID-19 disease among patients with HMs and B-cell lymphopenia.

The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.

Determining the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods in the Northeastern region of Hungary.

Objective: Identifying hypertension in children and providing treatment for it have a marked impact on the patients' long-term cardiovascular outcomes. The global prevalence of childhood hypertension is increasing, yet its investigation has been rather sporadic in Eastern Europe. Therefore, our goal was to determine the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods. Methods: We evaluated data from 3 to 18-year-old children who visited the University of Debrecen Clinical Center's hospital throughout a 15-year study period (n = 92,198; boys/girls: 48/52%). Results: We identified a total of 3,687 children with hypertension (2,107 boys and 1,580 girls), with a 4% calculated prevalence of hypertension in the whole study population and a higher prevalence in boys (4.7%) as compared to girls (3.2%). Among boys we found an increasing prevalence in consecutive age groups in the study population, but among girls the highest prevalences are identified in the 12-15-year age group. Markedly higher BMI values were found in hypertensive children as compared to non-hypertensives in all age groups. Moreover, significantly higher total cholesterol (4.27 ± 0.95 vs. 4.17 ± 0.88 mmol/L), LDL-C (2.62 ± 0.79 vs. 2.44 ± 0.74 mmol/L) and triglyceride (1.2 (0.85-1.69) vs. 0.94 (0.7-1.33) mmol/L), and lower HDL-C (1.2 ± 0.3 vs. 1.42 ± 0.39 mmol/L) levels were found in hypertensive children. Furthermore, significantly higher serum uric acid levels were found in children with hypertension (299.2 ± 86.1 vs. 259.9 ± 73.3 µmol/L), while glucose levels did not differ significantly. Conclusion: Our data suggest that the calculated prevalence of childhood hypertension in our region is comparable to data from other European countries and is associated with early metabolic disturbances. Data mining is an effective method for identifying childhood hypertension and its metabolic consequences.

Relationship between arterial stiffness and regular physical activity / Az artériás érfali merevség és a rendszeres testmozgás kapcsolata.

Összefoglaló. A cardiovascularis megbetegedések kialakulását és progresszióját jelentosen befolyásolja az életmód, ezen belül a fizikai aktivitás. A rendszeres testmozgás csökkenti a szív- és érrendszeri kórképek kockázatát, többek között a magas vérnyomásra, a zsíranyagcsere-eltérésekre és az elhízásra gyakorolt kedvezo hatásán keresztül, továbbá független tényezo a cardiovascularis halálozás szempontjából is. Az artériás érfali merevség az elasztikus artériák falát alkotó extracelluláris mátrix degeneratív eltéréseinek következtében alakul ki a különbözo kockázati tényezok hatására. Korábban, különbözo populációkon már igazolták az érfali merevség prediktív értékét a cardiovascularis események kialakulásának tekintetében. A pulzushullám-terjedési sebesség mérése a leggyakrabban alkalmazott módszer az érfali merevség meghatározására. A pulzushullám-terjedési sebesség mérésének hasznát a cardiovascularis kimenetel és élettartam becslésében számos populációs szintu követéses vizsgálat igazolja. Jelen munkánkban áttekintjük a rendszeres fizikai aktivitás, az érfali merevség, az érelmeszesedés és a cardiovascularis események közötti összefüggéseket. Összefoglaljuk az edzésnek és az érfali merevség paramétereinek kapcsolatát egészséges populáción vizsgáló legfontosabb tanulmányok eredményeit. Megállapítjuk, hogy az érfali merevség figyelemre méltó, érdekes biomarker a cardiovascularis kockázat becslése során a rendszeresen sportoló személyek esetén is. Mindezek alapján, tekintve annak prognosztikai hasznát, felmerül a pulzushullám-terjedési sebesség mérésének beillesztése a klinikai döntéshozatali folyamatba mind amator, mind professzionális sportolók esetében. Orv Hetil. 2021; 162(16): 615-622. Summary. The development and progression of cardiovascular disorders is importantly dependent on lifestyle factors, including physical activity. Regular physical activity decreases cardiovascular morbidity by ameliorating risk factors such as hypertension, dyslipidemia and obesity, moreover, also independently affects cardiovascular mortality. Arterial stiffness results from a degenerative process affecting mainly the extracellular matrix of elastic arteries under the effect of risk factors. Previously, the independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in various populations. Pulse wave velocity is the most commonly used method for the assessment of arterial stiffness. The value of measuring pulse wave velocity to predict cardiovascular health outcomes and longevity has been established in several population-based longitudinal studies. In this review, we summarize the main associations between regular physical exercise, arterial stiffness, atherosclerotic burden and incident cardiovascular events. We cite findings from the major studies focusing on the effect of training on arterial stiffness parameters in healthy subjects. We conclude that arterial stiffness is emerging as an interesting biomarker for cardiovascular risk stratification in subjects doing regular physical activity. Therefore, the incorporation of pulse wave velocity measurement into clinical decision-making could be indicated in the case of both amateur and professional athletes, given the prognostic information it provides. Orv Hetil. 2021; 162(16): 615-622.

The first local experiences with rheopheresis treatment / A rheopheresiskezeléssel szerzett elso hazai tapasztalatok.

Összefoglaló. Háttér: A rheopheresis egy szelektív, extracorporalis, kettos kaszkádfiltrációs eljárás, mely elozetes plazmaszeparációt követoen egy speciális filter segítségével kivonja a vérplazmából a hiperviszkozitásért felelos komponenseket, úgymint alacsony suruségu lipoprotein, lipoprotein(a), triglicerid, koleszterin, fibrinogén, α2-makroglobulin, Von Willebrand-faktor, immunglobulin-M. Módszer és Betegek: Klinikánkon az elmúlt 5 évben MONET filter alkalmazásával összesen 80 kezelést végeztünk hiperviszkozitással összefüggo, idoskori száraz maculadegeneratióban, diabeteses alsó végtagi fekélyben, illetve neuropathiában. Eredmények: A dolgozatban beszámolunk kedvezo klinikai tapasztalatainkról, a viszkozitás, a klinikai tünetek és az elektroneurográfiai paraméterek tükrében. Orv Hetil. 2021; 162(10): 375-382. BACKGROUND: Rheopheresis is a selective, extracorporeal, double cascade filtration method. After a previous plasma separation, with the help of a special filter it extracts compounds from blood plasma which are responsible for hyperviscosity such as low-density lipoprotein, lipoprotein(a), triglyceride, cholesterine, fibrinogen, α2-macroglobulin, Von Willebrand factor, immunoglobulin M. METHOD AND PATIENTS: In the past 5 years, with the application of MONET filter we performed 80 therapies to treat age-related macula degeneration, diabetic foot ulcers and neuropathy which are complicated with hyperviscosity. RESULTS: The review describes our benefical clinical experiences in consideration of viscosity, clinical symptoms and electroneurography parameters. Orv Hetil. 2021; 162(10): 375-382.

Influence of angiotensin-converting enzyme inhibition on reversibility of alterations in arterial wall and cognitive performance associated with early hypertension: A follow-up study.

The importance of optimal blood pressure control for preventing or reducing the impairment of vascular and cognitive functions is well known. However, the reversibility of early alterations in vascular and cognitive functions through antihypertensive agents is under-investigated. In this study, we evaluated the influence of 3 months of angiotensin-converting enzyme (ACE) inhibition treatment on the morphological and functional arterial wall and cognitive performance changes in 30 newly diagnosed primary hypertensive patients.Common carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were detected by ultrasonography. Arterial stiffness indicated by augmentation index (AIx) and pulse wave velocity (PWV) was assessed by arteriography. Cognitive functions were assessed by neuropsychological examination.The executive function overall score was significantly higher at 3-month follow-up than at baseline (median, 0.233 (IQR, 0.447) vs -0.038 (0.936); P = .001). Three-month ACE inhibition did not produce significant improvement in IMT, FMD, AIx and PWV values. Significant negative associations were revealed between IMT and complex attention (r = -0.598, P = .0008), executive function (r = -0.617, P = .0005), and immediate memory (r = -0.420, P = .026) overall scores at follow-up. AIx had significant negative correlations with complex attention (r = -0.568, P = .001), executive function (r = -0.374, P = .046), and immediate memory (r = -0.507, P = .005). PWV correlated significantly and negatively with complex attention (r = -0.490, P = .007).Timely and effective antihypertensive therapy with ACE inhibitors has significant beneficial effects on cognitive performance in as few as 3 months. Early ACE inhibition may have an important role in the reversal of initial impairments of cognitive function associated with hypertension-induced vascular alterations.

[Immunoadsorption in a patient with dilated cardiomyopathy. The first case in Hungary]. / Dilatatív cardiomyopathia immunadszorpciós kezelése. Az elso magyarországi eset kapcsán.

Dilated cardiomyopathy is the main cause of heart transplantation. The etiology is unknown in almost half of the cases. Many cardiac specific antibodies have been identified till now which can cause decreased cardiac function, ventricular tachycardia or sudden heart death. The prognosis of DCM is poor despite the development of medical treatment. Immunoadsorption is hopeful since, with the removal of antibodies, cardiac function and NYHA class can improve and LVAD/heart transplantation-free survival can be prolonged. At the University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Division of Angiology, Intensive Care and Therapeutic Apheresis Unit we performed the first immunoadsorption. Our patient was a 43-year-old man with idiopathic dilated cardiomyopathy, NYHA class IV, a heart transplantation candidate, whose cardiac specific antibody, type IgG was indentified by Western blot. Before the treatment he had ejection fraction of 18%. Discussing with his cardiologists we decided for immunoadsorption therapy. We performed 5 cycles on consecutive days in Intensive Care Unit. After 1 month we detected improvement in exercise capacity. We detected improvement in isovolemic contraction (from 465 mmHg/s to 575 mmHg/s), increased stroke volume (from 49 ml to 66 ml). After 3 months we repeated SPECT investigation which showed improvement in ejection fraction, from 18% to 32%. Orv Hetil. 2018; 159(13): 532-536.