المؤلفون: Guntram Schernthaner, Naim Shehadeh, Alexander S. Ametov, Anna V. Bazarova, Fahim Ebrahimi, Peter Fasching, Andrej Janež, Péter Kempler, Ilze Konrāde, Nebojša M. Lalić, Boris Mankovsky, Emil Martinka, Dario Rahelić, Cristian Serafinceanu, Jan Škrha, Tsvetalina Tankova, Žydrūnė Visockienė

المصدر: Cardiovascular Diabetology, Vol 19, Iss 1, Pp 1-17 (2020)

مصطلحات موضوعية: Type 2 diabetes, Cardiorenal protection, Glucose lowering drugs, Clinical inertia, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium–glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12933-020-01154-wTest; https://doaj.org/toc/1475-2840Test

الوصول الحر: https://doaj.org/article/0e1a0b51ae0646099e803da351dd7ca0Test

المؤلفون: Jelena Bogdanović, Milika Ašanin, Gordana Krljanac, Nebojša M. Lalić, Aleksandra Jotić, Sanja Stanković, Nataša Rajković, Ljubica Stošić, Iva Rasulić, Jelena Milin, Dragana Popović, Ljiljana Bogdanović, Katarina Lalić

المصدر: Cardiovascular Diabetology, Vol 18, Iss 1, Pp 1-12 (2019)

مصطلحات موضوعية: Diabetes, Acute hyperglycemia, Left ventricle, Multilayer strain, Two-dimensional speckle tracking, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Background Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease. Methods The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12933-019-0876-3Test; https://doaj.org/toc/1475-2840Test

الوصول الحر: https://doaj.org/article/90b9629c05694b34a2ec44465392c946Test

المؤلفون: Katarina Lalić, Aleksandra Jotić, Nataša Rajković, Sandra Singh, Ljubica Stošić, Ljiljana Popović, Ljiljana Lukić, Tanja Miličić, Jelena P. Seferović, Marija Maćešić, Jelena Stanarčić, Milorad Čivčić, Iva Kadić, Nebojša M. Lalić

المصدر: International Journal of Endocrinology, Vol 2015 (2015)

مصطلحات موضوعية: Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1687-8337Test; https://doaj.org/toc/1687-8345Test

الوصول الحر: https://doaj.org/article/2a88052a2bbf4696bf48697ed67b947eTest

المؤلفون: Nemanja Isajev, Vesna Bjegovic-Mikanovic, Zoran Bukumiric, David Vrhovac, Nebojsa M. Lalic

المصدر: International Journal of Environmental Research and Public Health; Volume 19; Issue 8; Pages: 4436

مصطلحات موضوعية: diabetes type 2, clinical inertia, diabetes care, physician inertia, primary care physicians, glycemic control

جغرافية الموضوع: agris

الوصف: With the growing prevalence and complex pathophysiology of type 2 diabetes, many patients fail to achieve treatment goals despite guidelines and possibilities for treatment individualization. One of the identified root causes of this failure is clinical inertia. We explored this phenomenon, its possible predictors, and groups of patients affected the most, together with offering potential paths for intervention. Our research was a cross-sectional study conducted during 2021 involving 52 physicians and 543 patients of primary healthcare institutions in Belgrade, Serbia. The research instruments were questionnaires based on similar studies, used to collect information related to the factors that contribute to developing clinical inertia originating in both physicians and patients. In 224 patients (41.3%), clinical inertia was identified in patients with poor overall health condition, long diabetes duration, and comorbidities. Studying the changes made to the treatment, most patients (53%) had their treatment adjustment more than a year ago, with 19.3% of patients changing over the previous six months. Moreover, we found significant inertia in the treatment of patients using modern insulin analogues. Referral to secondary healthcare institutions reduced the emergence of inertia. This assessment of primary care physicians and their patients pointed to the high presence of clinical inertia, with an overall health condition, comorbidities, diabetes duration, current treatment, last treatment change, glycosylated hemoglobin and fasting glucose measuring frequency, BMI, patient referral, diet adjustment, and physician education being significant predictors.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/ijerph19084436Test

الإتاحة: https://doi.org/10.3390/ijerph19084436Test

المؤلفون: Kasja Pavlovic, Nina Krako Jakovljevic, Andjelka M. Isakovic, Tijana Ivanovic, Ivanka Markovic, Nebojsa M. Lalic

المصدر: Frontiers in Pharmacology, Vol 13 (2022)

مصطلحات موضوعية: metformin, mitochondria, skeletal muscle, therapeutic concentration, respirometry, Therapeutics. Pharmacology, RM1-950

الوصف: Metformin is an oral antidiabetic agent that has been widely used in clinical practice for over 60 years, and is currently the most prescribed antidiabetic drug worldwide. However, the molecular mechanisms of metformin action in different tissues are still not completely understood. Although metformin-induced inhibition of mitochondrial respiratory chain Complex I and activation of AMP-activated protein kinase have been observed in many studies, published data is inconsistent. Furthermore, metformin concentrations used for in vitro studies and their pharmacological relevance are a common point of debate. The aim of this study was to explore the effects of different metformin concentrations on energy metabolism and activity of relevant signaling pathways in C2C12 muscle cells in vitro. In order to determine if therapeutic metformin concentrations have an effect on skeletal muscle cells, we used micromolar metformin concentrations (50 µM), and compared the effects with those of higher, millimolar concentrations (5 mM), that have already been established to affect mitochondrial function and AMPK activity. We conducted all experiments in conditions of high (25 mM) and low glucose (5.5 mM) concentration, in order to discern the role of glucose availability on metformin action. According to our results, micromolar metformin treatment did not cause Complex I inhibition nor AMPK activation. Also, cells cultured in low glucose medium were more sensitive to Complex I inhibition, mitochondrial membrane depolarization and AMPK activation by millimolar metformin, but cells cultured in high glucose medium were more prone to induction of ROS production. In conclusion, even though suprapharmacological metformin concentrations cause Complex I inhibition and AMPK activation in skeletal muscle cells in vitro, therapeutic concentrations cause no such effect. This raises the question if these mechanisms are relevant for therapeutic effects of metformin in skeletal muscle.

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2022.930308/fullTest; https://doaj.org/toc/1663-9812Test; https://doaj.org/article/6ba629e3020b432c920796c884b58d38Test

الإتاحة: https://doi.org/10.3389/fphar.2022.930308Test
https://doaj.org/article/6ba629e3020b432c920796c884b58d38Test

المؤلفون: Nina Krako Jakovljevic, Kasja Pavlovic, Aleksandra Jotic, Katarina Lalic, Milica Stoiljkovic, Ljiljana Lukic, Tanja Milicic, Marija Macesic, Jelena Stanarcic Gajovic, Nebojsa M. Lalic

المصدر: International Journal of Molecular Sciences; Volume 22; Issue 12; Pages: 6642

مصطلحات موضوعية: type 2 diabetes, insulin resistance, mitochondria, respiration, respiratory capacity, liver, skeletal muscle, blood cells, exercise, diabetes therapy

جغرافية الموضوع: agris

الوصف: Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

وصف الملف: application/pdf

العلاقة: Molecular Endocrinology and Metabolism; https://dx.doi.org/10.3390/ijms22126642Test

الإتاحة: https://doi.org/10.3390/ijms22126642Test

المؤلفون: Jelena P. Seferovic, Milorad Tesic, Visnja Lezaic, Petar M. Seferovic, Nebojsa M. Lalic

المصدر: Journal of International Medical Research, Vol 49 (2021)

مصطلحات موضوعية: Medicine (General), R5-920

الوصف: Contrast-induced nephropathy (CIN) is the impairment of kidney function defined as a serum creatinine increase of 25% or 44 µmol/L compared with baseline, usually occurring 24 to 48 hours after the use of intravenous contrast. Important risk factors for CIN include female sex, advanced age (>65 years), type 2 diabetes (T2D), kidney disease, advanced heart failure, and intravascular volume depletion. We herein present a male patient with T2D, moderately reduced renal function, no albuminuria, and a positive echocardiography stress test. He underwent percutaneous coronary intervention (PCI), and two drug-eluting stents (in the left anterior descending coronary artery) and three bare-metal stents (in the right coronary artery) were implanted. Despite adequate rehydration (0.9% intravenous NaCl with 8.4% sodium bicarbonate) before and after the procedures, he developed irreversible kidney injury after coronary angiography and PCI. This case report demonstrates the unpredictable clinical course of CIN. Patients with T2D are at high risk for the occurrence of CIN, so careful clinical assessment is recommended with global renal functional reserve evaluation.

العلاقة: https://doi.org/10.1177/03000605211033177Test; https://doaj.org/toc/1473-2300Test; https://doaj.org/article/450345723cb1414484ea399f9d4f92fbTest

الإتاحة: https://doi.org/10.1177/03000605211033177Test
https://doaj.org/article/450345723cb1414484ea399f9d4f92fbTest

المؤلفون: Dominik Pesta, Tomas Jelenik, Oana-Patricia Zaharia, Pavel Bobrov, Sven Görgens, Kálmán Bódis, Yanislava Karusheva, Nina Krako Jakovljevic, Nebojsa M. Lalic, Daniel F. Markgraf, Volker Burkart, Karsten Müssig, Birgit Knebel, Jörg Kotzka, Jürgen Eckel, Klaus Strassburger, Julia Szendroedi, Michael Roden

المصدر: Frontiers in Endocrinology, Vol 12 (2021)

مصطلحات موضوعية: diabetes mellitus, physical activity, single nucleotide polymorphism, insulin sensitivity, mitochondrial function, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: The rs540467 SNP in the NDUFB6 gene, encoding a mitochondrial complex I subunit, has been shown to modulate adaptations to exercise training. Interaction effects with diabetes mellitus remain unclear. We assessed associations of habitual physical activity (PA) levels with metabolic variables and examined a possible modifying effect of the rs540467 SNP. Volunteers with type 2 (n=242), type 1 diabetes (n=250) or normal glucose tolerance (control; n=139) were studied at diagnosis and subgroups with type 1 (n=96) and type 2 diabetes (n=95) after 5 years. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, oxygen uptake at the ventilator threshold (VO2AT) by spiroergometry and PA by questionnaires. Translational studies investigated insulin signaling and mitochondrial function in Ndufb6 siRNA-treated C2C12 myotubes, with electronic pulse stimulation (EPS) to simulate exercising. PA levels were 10 and 6%, VO2AT was 31% and 8% lower in type 2 and type 1 diabetes compared to control. Within 5 years, 36% of people with type 2 diabetes did not improve their insulin sensitivity despite increasing PA levels. The NDUFB6 rs540467 SNP modifies PA-mediated changes in insulin sensitivity, body composition and liver fat estimates in type 2 diabetes. Silencing Ndufb6 in myotubes reduced mitochondrial respiration and prevented rescue from palmitate-induced insulin resistance after EPS. A substantial proportion of humans with type 2 diabetes fails to respond to rising PA with increasing insulin sensitivity. This may at least partly relate to a polymorphism of the NDUFB6 gene, which may contribute to modulating mitochondrial function.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01055093. The trial was retrospectively registered on 25th of January 2010.

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2021.693683/fullTest; https://doaj.org/toc/1664-2392Test; https://doaj.org/article/fa181e3f185b4da2a7313370833cc71cTest

الإتاحة: https://doi.org/10.3389/fendo.2021.693683Test
https://doaj.org/article/fa181e3f185b4da2a7313370833cc71cTest

المؤلفون: Dubravka Mandic, Vesna Bjegovic-Mikanovic, Dejana Vukovic, Bosiljka Djikanovic, Zeljka Stamenkovic, Nebojsa M. Lalic

المصدر: PeerJ, Vol 8, p e9495 (2020)

مصطلحات موضوعية: Physical activity, University students, Web-based intervention, Motivational interview, Multicomponent intervention, Medicine, Biology (General), QH301-705.5

الوصف: Background Regular physical activity supports healthy behavior and contributes to the reduction of preventable diseases. Students in their social transition period are the ideal groups for interventions. The higher education period, associated with demanding changes and poor time management, results in a low level of physical activity. In this age, social media usually are a suitable channel of communication and multicomponent interventions are the most desirable. It has not been sufficiently investigated how effective a Web-based approach is among university students when it comes to physical activity in the long-term period. We combined a Web-based approach with motivational interviews and tested these two interventions together and separate to assess their impact on improving the physical activity of medical students 1 year after the intervention. Methods All 514 first-year students at the Faculty of Medicine in Belgrade were invited to fill in a baseline questionnaire. Also, they underwent measurement of weight, height and waist circumference. After that, students selected a 6 months intervention according to their preference: Intervention through social media (Facebook) (Group 1) or combined with a motivational interview (Group 2). Group 3 consisted of students without any intervention. One year after completion of the 6 months intervention period, all students were invited to a second comprehensive assessment. Analyses were performed employing a wide range of statistical testing, including direct logistic regression, to identify determinants of increased physical activity measured by an average change of Metabolic Equivalent of Task (MET). This outcome measure was defined as the difference between the values at baseline and one year after completion of the 6 months intervention period. Results Due to a large number of potential determinants of the change of MET, three logistic regression models considered three groups of independent variables: basic socio-demographic and anthropometric data, intervention ...

العلاقة: https://peerj.com/articles/9495.pdfTest; https://peerj.com/articles/9495Test/; https://doaj.org/toc/2167-8359Test; https://doaj.org/article/c89a309df3174ad9b9f94649d4104e07Test

الإتاحة: https://doi.org/10.7717/peerj.9495Test
https://doaj.org/article/c89a309df3174ad9b9f94649d4104e07Test

المؤلفون: Antonio Ceriello, Eberhard Standl, Doina Catrinoiu, Baruch Itzhak, Nebojsa M. Lalic, Dario Rahelic, Oliver Schnell, Jan Škrha, Paul Valensi

المصدر: Cardiovascular Diabetology, Vol 19, Iss 1, Pp 1-7 (2020)

مصطلحات موضوعية: Cardiovascular complications, COVID-19, Diabetes, Intensive Care Unit, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: In the pandemic “Corona Virus Disease 2019” (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.

العلاقة: http://link.springer.com/article/10.1186/s12933-020-01089-2Test; https://doaj.org/toc/1475-2840Test; https://doaj.org/article/5b5fef5082744473bf5853653045710eTest

الإتاحة: https://doi.org/10.1186/s12933-020-01089-2Test
https://doaj.org/article/5b5fef5082744473bf5853653045710eTest