Cardioprotective mechanisms of sodium-glucose cotransporter 2 inhibitors

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM

The role of bile acids and intestinal microbiota in metabolic transformations after gastric bypass surgery

Today, the positive impact of bariatric surgery on the course of type 2 diabetes mellitus has been studied in detail. At the same time, not only the effect of direct weight loss and the incretin theory, but also other mechanisms for normalizing glycemia are being actively discussed. Thus, special attention is paid to the metabolism of bile acids and their influence on various indicators of homeostasis, including carbohydrate metabolism. After bariatric interventions of the bypass type, the passage of bile through the gastrointestinal tract, as well as its interaction with food masses, changes significantly, which served as the basis for studying this phenomenon. The information accumulated to date indicates enormous changes occurring not only in the anatomy, but also in the biology of the gastrointestinal tract after bariatric bypass surgery. The composition of the intestinal microbiota and the composition of bile masses undergo significant changes. Most of the works available today suggest that these changes are the cause of a number of metabolic rearrangements, and directly affect carbohydrate metabolism. This issue is still under study and accumulation of the necessary information, but today it can be stated with confidence that the role of bile passage, bile acid circulation and restructuring of the intestinal microbiota in the regulation of carbohydrate metabolism and energy balance after bariatric bypass surgery is of extreme importance

EVALUATION OF THE IMPACT OF DRUG THERAPY FOR OBESITY ON THE CLINICAL MANIFESTATIONS OF KNEE OSTEOARTHRITIS IN OVERWEIGHT WOMEN

Objective: to evaluate the impact of orlistat therapy on the clinical manifestations of knee osteoarthritis (OA) in obese patients.Subjects and methods. The investigation enrolled 50 women aged 45–65 years with Kellgren–Lawrence Stages II–III knee OA and obesity [body mass index (BMI) > 30 kg/m2] who were randomized into 2 groups: 1) 25 patients who took Orlistat in a dose of 120 mg (one capsule) thrice daily for 6 months in conjunction with a low-calorie diet and exercise; 2) 25 patients who received only non-drug therapy for obesity (a low-calorie diet and exercise). The investigators assessed anthropometric measures, WOMAC index, and health status using a visual analogue scale.Results and discussion. After 6 months, group 1 had more marked weight loss than group 2: 10.0% (mean 10.5 kg) and 0.8% (mean 1 kg) respectively. Orlistat also provided more pronounced reduction of WOMAC pain scores, functional insufficiency and WOMAC index than non-pharmacological therapy (by 52.2% and 28.8%, р ≤ 0.05, by 51 and 18%, р ≤ 0.05 and by 51 and 19%, p = 0.006 respectively). Moreover, group 1 showed significant improvement of quality of life as compared to group 2 (p < 0.001). The tolerability of Orlistat was good; only two patients reported diarrhea due to dietary errors (fat intake), which required no drug discontinuation.Conclusion. The investigation has demonstrated that body weight loss provided by appropriate medications leads to the regress of clinical manifestations of knee OA in obese patients: pain relief and functional improvement. So drugs contributing to weight los, should be incorporated into treatment regimens for patients with OA and obesity

Possibilities of application a fixed combination of alogliptin and pioglitazone for type 2 diabetes mellitus treatment

Hyperglycemia in T2DM is based on three main mechanisms: insulin resistance, progressive β-cell dysfunction, and excess glucose production by the liver.The onset of T2DM is usually preceded by a long period of insulin resistance. Prescribing sugar drugs that affect different links of pathogenesis, reducing a steady decrease in glycemia. To date, in clinical practice, various combinations of hypoglycemic drugs are used, the choice of which is determined by the characteristics of the course of diabetes in the patient, the presence of concomitant diseases and complications of diabetes, as well as the dominant clinical problem. This resolution provides an expert council opinion on the feasibility of using a combination of alogliptin and pioglitazone in patients with type 2 diabetes

Draft of Russian Clinical Practice Guidelines «Male hypogonadism»

Hypogonadism in males, defined as a decrease in serum testosterone levels in combination with characteristic symptoms and/or signs, can be observed with pathological changes in the testicles and/or pituitary gland, such as Klinefelter’s syndrome, Kallman’s syndrome, as well as in men with metabolic (obesity, diabetes mellitus) or iatrogenic disorders leading to a decrease in androgen production. The draft guidelines cover the extensive range of pathologies that cause hypogonadism development (testosterone deficiency) and focus on its clinical variants, which make up the majority of cases of hypogonadism observed in men. The authors and reviewers are an interdisciplinary group of experts, consisting of endocrinologists, andrologists, urologists - members of the «Russian Association of Endocrinologists» and «Men’s and Reproductive Health» public organizations.Clinical guidelines contain the most reliable evidence available to experts at the time of writing. Nevertheless, recommendations cannot replace clinical experience, and deciding on the start of treatment, choosing a method of therapy, or a drug should always consider the individual characteristics of a specific patient

Prevalence of carbohydrate metabolism disorders in patients with new coronavirus infection

BACKGRAUND: There is evidence of a multifactorial effect of SARS-CoV2 on carbohydrate metabolism with the development of hyperglycemia and the weighting of COVID19 even in people without DM.AIMS: Assess the prevalence of disorders carbohydrate metabolism (DCM) in hospitalized patients with a new coronavirus infection without a history of DM.MATERIALS AND METHODS: Patients with PCR-confirmed diagnosis of COVID19 aged 18-75 years (n=72) without a history of diabetes were examined. Observation was carried out from the moment of hospitalization to discharge. Patients were collected anamnesis data, laboratory and instrumental studies, HbA1c, fasting plasma glucose (FPG), postprandial glycemia.RESULTS: The prevalence of DCM (HbA1c≥6%) in 72 patients with COVID19 without a history of diabetes admitted to the hospital was 41,7%, while HbA1c ≥6,5% had 8,3%. The median HbA1c in the moderate-flow group was 5,7% [5,3–6,0], and in the severe-flow group it was 6,0% [5,8–6,2] (p=0,008). Participants were divided into groups according to the level of HbA1c≥6% and < 6%. The examined patients showed a high prevalence of risk factors for developing DM: age over 45 years — 83,3%, cardiovascular diseases — 46,3%, obesity — 50%. The study groups didn’t differ statistically in terms of risk factors for DM. In the group with HbA1c≥6%, FPG≥6,1 mmol / l on the second day and postprandial glycemia ≥7,8 mmol/l were observed in more cases than in the group with HbA1c<6% (39,1% vs 12,9%, p=0,051 and 47,8% vs 3,2%, p=0,0001, respectively). The prevalence of DCM in HbA1c was higher than in FPG (41,7% vs 29,2%, p=0,006). On the seventh day, the number of patients with FPG ≥ 6,1 mmol / l in the first group decreased from 39,1% to 4,4% (p=0,01), and in the second group-from 12,9% to 9,7% (p=1,0). There was a direct correlation between the level of HbA1c and C-reactive protein (r=0,271; p=0,048), and an inverse correlation with the content of lymphocytes in the blood (r=-0,25; p=0,068).CONCLUSIONS: In patients with a new coronavirus infection without a history of DM, a high prevalence of DCM was detected — 41,7%. Against the background of comparability of the studied groups by risk factors for DM, an increase in HbA1c, FPG and postprandial glycemia is a manifestation of transient hyperglycemia. Given the high prevalence of DCM, it can be assumed that SARS-CoV2 has diabetogenic properties

Pancreatic exocrine insufficiency in diabetes mellitus

Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT)

The advisory board resolution on the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes

Type 2 diabetes is characterized by increasing incidence and prevalence all-over the world. Current therapeutic management of type 2 diabetes is complex and is based not only on glycemic control, but also on cardiovascular and renal risks reduction. In previous years the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) increased in Russian Federation. Some manufacturers of the most widely used GLP-1 RA reported the supply decline in several countries. On Advisory board with participation of the Russian Endocrinology Association members the topics of SGLT2i and GLP-1 RA use in type 2 diabetes were discussed. The experts made conclusion that the decrease in access to GLP-1 RA does not pose serious risk for treatment of type 2 diabetes patients. SGLT2i show benefits in risk reduction of HF and CKD progression compering to GLP-1 RA, and in general show comparable efficacy in risk reduction of ACVD outcomes.  SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups

Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Inhibitors of the sodium-glucose cotransporter type 2 (SGLT2i) are a modern class of antihyperglycemic drugs with an insulin-independent mechanism of action. Due to its ability to effectively lower blood glucose levels, improve a number of other cardiometabolic parameters (body weight, blood pressure, uric acid), as well as reduce cardiovascular and renal risks, SGLT2i have become drugs of choice for many of patients with type 2 diabetes mellitus (T2DM). Meanwhile, along with the generally recognized classes-effects of this group of drugs, there are intragroup features, including those associated with their different selectivity in sodium-glucose cotransporters of types 1 and 2 (SGLT1 and SGLT 2). For example, one of the most studied SGLT2i, canagliflozin, in addition to its inhibitory activity against SGLT2, can also moderately block SGLT1 in the intestine and kidneys that could give a maximum efficiency in the control glycemia and others cardiometabolic parameters. In addition, canagliflozin improves not only cardiovascular, but also renal prognosis in patients with T2DM, which is reflected in the corresponding indications in the summary of product characteristics of the drug. This document summarize the established and new data regarding the efficacy and safety of canagliflozin, as well as its place in the treatment of T2DM