SGLT2 inhibitors: a promising class of antidiabetic agents

The international guidelines for the management of type 2 diabetes mellitus have seen many changes over the last decade. They have moved from a strict glycemic control in all patients with diabetes to a more individualized approach of the diabetic patient. These changes are the result of some trials which have demonstrated, for example, that in patients with long-standing type 2 diabetes a strict glycemic control may increase the risk of complications, such as hypoglycemia and cardiovascular events1-3. While glucose lowering prevents the appearance of microvascular complications, its impact is less significant on the cardiovascular and renal complications. The most preferred oral antidiabetic drug is undoubtedly metformin. There are six antidiabetic drug classes currently recommended by the American and European international societies, in addition to metformin: sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, sulfonylureas, thiazolidinediones, and insulin. SGLT2 inhibitors are a promising new class of antidiabetic drugs, that have entered very recently in the diabetes therapeutic armamentarium. These drugs enhance the urinary glucose excretion and decrease hyperglycemia, acting independently from insulin and being effective in all diabetic patients with preserved renal function. They have a favorable efficacy-to adverse event profile in type 2 diabetes patients with moderate-to-high risk. Currently, there are four SGLT2 inhibitors approved by the US Food and Drug Administration (FDA) and the European Medicines Agency: canaglifozin, dapaglifozin, empaglifozin, and ertuglifozin3. These may be used as monotherapy or in combination with other antidiabetic agents.SGLT2 inhibitors have also pleiotropic effects, such as reducing body weight by 2-3 Kg, decreasing the blood pressure (both systolic and diastolic), decreasing plasma triglycerides, increasing HDL cholesterol, attenuating some factors associated with nonalcoholic steatohepatitis and nonalcoholic liver disease, improving the whole-body sodium balance and volume status by stimulating the natriuresis, which leads further to a better endothelial function by reducing the vascular stiffness1. Due to these effects, SGLT2 inhibitors are useful especially in obese patients with arterial hypertension. They may be indicated as single or combination therapy, with other antidiabetic agents, and are contraindicated in patients with kidney failure1 with a GFR < 45 mL/min/1.73 m2. Regarding the glucose control, in a meta-analysis, the HbA1c reduction at 24-weeks was higher in studies that included younger patients, with a shorter duration of diabetes and a higher body mass index, HbA1c and basal glucose4. The cardiovascular benefits of SGLT2 inhibitors have been demonstrated by some major trials, such as EMPA-REG OUTCOME trial (Empaglifozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients)5 and CANVAS (Canaglifozin Cardiovascular Assessment Study)6. EMPA-REG OUTCOME trial has found a reduced incidence of cardiovascular death in diabetic patients treated with Empaglifozin and also a decreased rate of hospitalization for heart failure5. CANVAS Program has showed also a decreased rate of hospitalization for heart failure in patients treated with Canaglifozin6. This is extremely important, especially for patients with type 2 diabetes and already established cardiovascular diseases, as they may benefit most from the treatment with SGLT2 inhibitors. The main side effects of SGLT2 inhibitors consist in the increased risk of genital infections (up to four-fold in clinical trials). Other side effects, more rarely, may be the risk of hypoglycemia, diabetic ketoacidosis, bone fractures (with Canaglifozin). Recently, the US Food and Drug Administration warned about the risk of necrotizing fasciitis of the perineum (Fournier’s gangrene) in patients treated with SGLT2 inhibitors7. This is an extremely rare, but life-threatening infection of the tissues around the perineal muscles, nerves, fat and blood vessels. In conclusion, SGLT2 inhibitors are the newest antidiabetic drugs class, with cardiovascular benefits in a selected population of type 2 diabetes patients. There are ongoing studies with these antidiabetic agents expected to report their data in the near futur

Focusing on malignant tumors: September issue @ a glance

The September issue of the journal “Archives of the Balkan Medical Union“ is ready and has lots of interesting subjects for its readers. Diffuse large B‑cell lymphoma is a common form of non‑Hodgkin’s malignant lymphomas, occurring at all ages. Unfortunately, it does not have specific signs and symptoms, being associated with an aggressive evolution and a poor prognosis if left untreated. The study of Birceanu Corobea et al (Bucharest, Romania), “The clinical importance of PD‑L1 and PD‑1 expression in diffuse large B cell lymphoma“, investigated the role of PD‑1 (programmed cell death‑1) and PD‑L1 (programmed death‑ligand 1) in diffuse large B cell lymphoma. Their results suggest that PD‑1 and PD‑L1 could be potential biomarkers for targeted treatment in some patients diagnosed with diffuse large B‑cell lymphoma. Malignant lymphomas of the head and neck may raise therapeutic difficulties. In their minireview “Therapeutic methods used in the treatment of malignant lymphomas of the head and neck“, Tusaliu et colleagues, from the University of Medicine and Pharmacy “Carol Davila“, Bucharest, Romania, evaluated the therapeutic methods used in malignant lymphoma, such as conventional chemotherapy, radiotherapy, surgical treatment, salvage treatment, interferon treatment, monoclonal antibody treatment, medullar transplantation, and peptide treatment

Легочная паражение при системных васкулитах.

Pulmonary affectation in systemic vacculitis.Vasculitele sistemice sunt un grup heterogen de afecţiuni rare, cu tablou clinic complex şi variabil, caracterizate &icirc;n principal de infl amaţia peretelui vascular, ce are ca şi rezultat alterarea circulaţiei &icirc;n teritoriul respectiv şi apariţia ischemiei tisulare. Etiopatogenia este de obicei necunoscută, fi ind caracterizate de un sindrom infl amator intens. Fără intervenţie terapeutică rapidă, prognosticul vasculitelor este rezervat. Din punct de vedere al manifestărilor clinice, acestea sunt heterogene şi polimorfe, put&acirc;nd debuta cu semne generale de tip febră, artralgii sau stare generală alterată şi continua cu manifestări sistemice cum sunt ulcerele cutanate, erupţiile purpurice, iridociclită, glomerulonefrită etc. O categorie specială de manifestări clinice &icirc;n vasculite, mai puțin bine cunoscute, sunt cele determinate de afectarea pulmonară. Manifestările pulmonare sunt mai frecvente &icirc;n cadrul vasculitelor de vas mic, &icirc;n special cele ANCA pozitive, şi debutează iniţial nespecifi c, cu fenomene de tip dispnee, sinusită, epistaxis, tuse sau astm bronșic. Din cauza frecvenţei şi semnifi caţiei prognostice, evaluarea clinică, funcţională şi radiologică a aparatului respirator trebuie inclusă &icirc;n algoritmul de diagnostic al pacienţilor cu vasculite, &icirc;n special al celor cu ANCAЛегочная паражение при системных васкулитах

Diagnosis and management of pericardial effusion

Pericardial effusion is a common pathology in clinical practice. The etiology of pericardial effusion is diverse, from infectious diseases, malignancies, autoimmune diseases, chronic renal failure, to drug-related or after an invasive cardiac intervention. Clinical presentation of pericardial effusion is variable, depending on the volume of the fluid and the rate of accumulation. Clinical manifestations are dramatic if the pericardial fluid accumulates rapidly. Classical symptoms in pericardial effusion include pleuritic chest pain associated with dyspnea. In case of cardiac tamponade, orthopnea, jugular venous distension, pulsus paradoxus, hypotension, and shock appear. Transthoracic echocardiography is the gold standard investigation for the diagnosis of pericardial effusions. The echocardiographic signs of cardiac tamponade are represented by the collapse of the right atrium and right ventricle, respiratory alteration of mitral and tricuspid flow, and changes of the inferior vena cava. Management of pericardial effusion is guided by several factors, including hemodynamic impact and etiology. Pericardiocentesis guided by echocardiography is a life-saving procedure in cases of large pericardial effusions and cardiac tamponade. This is a review of the diagnosis and treatment of pericardial effusion

Pheochromocytoma – clinical manifestations, diagnosis and current perioperative management

Pheochromocytoma is a neuroendocrine tumor characterized by the excessive production of catecholamines (epinephrine, norepinephrine, and dopamine). The diagnosis is suspected due to hypertensive paroxysms, associated with vegetative phenomena, due to the catecholaminergic hypersecretion. Diagnosis involves biochemical tests that reveal elevated levels of catecholamine metabolites (metanephrine and normetanephrine). Functional imaging, such as 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG), has increased specificity in identifying the catecholamine-producing tumor and its metastases. The gold-standard treatment for patients with pheochromocytoma is represented by the surgical removal of the tumor. Before surgical resection, it is important to optimize blood pressure and intravascular volume in order to avoid negative hemodynamic events

Pelvic floor disorders in gynecological malignancies. An overlooked problem?

Cervical, endometrial, ovarian, vulvar, and vaginal cancers affect women of a broad age spectrum. Many of these women are still sexually active when their cancer is diagnosed. Treatment options for gynecological malignancies, such as gynecological surgery, radiation, and chemotherapy, are proven risk factors for pelvic floor dysfunction. The prevalence of urinary incontinence, fecal incontinence, and sexual dysfunction before cancer treatment is still unclear. Hypotheses have been raised in the literature that these manifestations could represent early symptoms of pelvic cancers, but most remain overlooked even in cancer surviving patients. The primary focus of therapy is always cancer eradication, but as oncological and surgical treatment options become more successful, the number of cancer survivors increases. The quality of life of patients with gynecological cancers often remains an underrated subject. Pelvic floor disorders are not consistently reported by patients and are frequently overlooked by many clinicians. In this brief review we discuss the importance of pelvic floor dysfunction in patients with gynecological malignant tumors

Health Tourism Contribution to the Structural Dynamics of the Territorial Systems with Tourism Functionality

AbstractThe study aims to identify the role of health tourism (SPA) in developing the territorial systems, characterized by the tourism functionality, in Romania, for the period 2000-2012, a period marked by spectacular transformations, especially for this economic sector. Tourism has now become a true economic engine, generating an increase in the functional complexity of the territorial system, which is based on exploiting tourism resources. To quantify how tourism has contributed to the economic development of these territorial systems in Romania a database of NACE codes was set up, specific for the tourism activity, for the period 2000-2012, for territorial mainframe systems with functionality resort. Based on this statistical support analyzes on the evolution of the number of companies, number of employees, turnover and profit were made. The results show the important role of health tourism in generating multiplier effects on other components of the economic subsystem. They were defined two categories of territorial systems: territorial systems where tourism plays a complementary role function and territorial systems in which health tourism has a preeminent role in the local economy

The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase

Intestinal microbiota – a possible contributor to cardiovascular diseases?

The intestinal microbiota represents an interesting and emergent field of research, with already known implications in metabolic and immunological functions. Recently, there is increasing evidence that specific gut microbial populations are associated with cardiovascular diseases. Numerous completed and ongoing studies aim to evaluate the potential of intestinal microbiota assessment to improve the prevention, diagnosis, and therapeutic arsenal of cardiovascular diseases, considering dysbiosis as a cardiovascular risk factor. There is strong evidence for a correlation between intestinal flora imbalance and metabolic changes secondary to bacterial metabolites. In this minireview, we discuss recent data about the connections between intestinal microbiota and cardiovascular disease