Prognostic factors for the carbohydrate metabolism normalization in patients with type 2 diabetes mellitus and obesity using liraglutide 3.0 mg per day

Background. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are innovative drugs that effectively reduce glycemic levels and overweight in patients with type 2 diabetes mellitus (T2DM). However, the criteria for predicting the hypoglycemic effect of this group of drugs have not been practically defined. Aim. To assess the factors contributing to the achievement the glycemia normalization in patients with diabetes mellitus and obesity by adding to antihyperglycemic therapy (AT) a drug from the GLP-1 RA group liraglutide 3.0 mg per day. Materials and methods. A single-center, prospective, non-randomized study was provided. The objects of the study were patients with T2DM and obesity (n=22). Liraglutide 3.0 mg per day was added to the current AT of patients. Initially, the parameters of carbohydrate metabolism, hormones of the incretin system on an empty stomach and during the mixed-meal test, insulin resistance using the euglycemic hyperinsulinemic clamp test, and body composition were studied. After 9 months of therapy, all studies were repeated and a search for possible predictors of the carbohydrate metabolism normalization was made. Results. The body mass index of patients decreased from 42.4 [37.7; 45.0] to 35.9 [33.0; 40.9] kg/m2. Fasting blood glucose and glycated hemoglobin levels decreased from 9.02 [7.40; 11.37] mmol/L and 7.85 [7.43; 8.65]% up to 5.90 [5.12; 6.18] mmol/L and 6.40 [5.90; 6.60]%, respectively. 14 (63.6%) patients reached normoglycemia. Insulin resistance according to the clamp test did not change over the study. Basal concentrations of oxyntomodulin, glycentin and the area under the GLP-1, oxyntomodulin, glycentin curve significantly decreased 9 months after liraglutide administration. The prognostic marker of the achievement of normoglycemia during therapy with liraglutide 3.0 mg/day is the level of endogenous GLP-15.5 pmol/L before the appointment of arGPP-1 therapy. Conclusion. The concentration of endogenous GLP-1 before the appointment of liraglutide therapy at a dose of 3.0 mg per day can be used for prediction the drug hypoglycemic effect and achieving normoglycemia possibility.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2»)

Aim To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients’ privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

Diabetic nephropathy: modern principles of classification, diagnosis and features of antihyperglycemic therapy

Статья посвящена современным подходам к терапии сахарного диабета, осложненного поражением почек. Сахарный диабет является важнейшей проблемой современной медицины, что прежде всего обусловлено высокой распространенностью заболевания среди трудоспособного населения. Диабетическая нефропатия – одно из тяжелых хронических осложнений диабета, повышающее инвалидизацию и смертность пациентов. Диабетическая нефропатия является основной причиной развития терминальной почечной недостаточности в развитых странах и со временем затрагивает около 30% пациентов. Поражение почек у больных сахарным диабетом встречается в 6-7% случаев из общего числа нефропатий у пациентов, получающих лечение в специализированном нефрологическом отделении многопрофильного стационара. Первые проявления диабетической нефропатии развиваются через 3-4 года от дебюта заболевания и достигают своего пика через 15-20 лет. Понятие «хроническая болезнь почек» включает в себя поражение почек независимо от первичного диагноза, характеризующееся такими основными диагностическими критериями, как экскреция альбумина с мочой и значения скорости клубочковой фильтрации, которые являются маркерами повреждения почек. Методы предупреждения прогрессирования диабетической нефропатии включают в себя общие мероприятия по изменению образа жизни, контроль гликемии и артериального давления, коррекцию нарушений липидного обмена в сочетании с нефропротективной терапией. В настоящее время при выборе терапии у больных сахарным диабетом 2 типа в сочетании с хронической болезнью почек наряду с приемом метформина предпочтение отдается ингибиторам натрий-глюкозного котранспортера 2-го типа и агонистам рецепторов глюкагоноподобного пептида-1, обладающим нефропротективным эффектом. The article is devoted to modern approaches to the treatment of diabetes mellitus complicated by kidney damage. Diabetes mellitus is the most important problem of modern medicine, which is primarily due to the high prevalence of the disease among the working-age population. Diabetic nephropathy is one of the severe chronic complications of diabetes, which increases the disability and mortality of patients. Diabetic nephropathy is the main cause of the development of end-stage renal failure in developed countries and eventually affects about 30% of patients. Kidney damage in patients with diabetes occurs in 6-7% of cases out of the total number of nephropathies in patients receiving treatment in a specialized nephrological department of a multidisciplinary hospital. The first manifestations of diabetic nephropathy develop 3-4 years after the onset of the disease, and reach their peak in 15-20 years. The concept of «chronic kidney disease» includes kidney damage regardless of the primary diagnosis and is characterized by such basic diagnostic criteria as urinary albumin excretion and glomerular filtration rate values, which are markers of kidney damage. Methods for preventing the progression of diabetic nephropathy include general measures to change the lifestyle, control of glycemia and blood pressure, correction of lipid metabolism disorders in combination with nephroprotective therapy. Currently, when choosing therapy in patients with type 2 diabetes mellitus in combination with chronic kidney disease, along with taking metformin, preference is given to sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists with a nephroprotective effect.

Prediabetes: challenges and opportunities

In the world, the number of patients with carbohydrate metabolism disorders is steadily growing. Over the past 10 years, the number of patients with diabetes mellitus in the world has more than doubled. Moreover, there is not only an increase in the number of patients with diabetes mellitus, predominantly type 2 diabetes, but also with prediabetes. The term «prediabetes» means impaired glucose tolerance and impaired fasting glycemia. To date, it is obvious that the development of prediabetes lead not only to the higher risk of diabetes mellitus in the future, but also of cardiovascular diseases. Factors that increase the risk of cardiovascular events in patients with prediabetes includeare the following: insulin resistance, accompanied by arterial hypertension and dyslipidemia, and postprandial hyperglycemia. Therefore, it is very important to timely identify patients from the risk group, diagnose and treat carbohydrate metabolism disorders already at the stage of prediabetes. Also it is very important to identify the patients from the risk group, diagnose and treat carbohydrate metabolism disorders at the stage of prediabetes. Treatment of patients with prediabetes implies, first of all, lifestyle modification (moderate hypocaloric nutrition with predominant restriction of fats and simple carbohydrates and regular physical activity of moderate intensity) in order to reduce weight. If lifestyle changes are ineffective, drug therapy may be prescribed. The article discusses the studies conducted to assess the effectiveness of lifestyle modification, as well as various options for antihyperglycemic therapy (metformin, glucagon-like peptide receptor agonists, alpha-glucosidase inhibitors, orlistat) for the treatment of patients with prediabetes. It also provides data on long-term follow-up of patients with prediabetes who received different treatment options.

Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New Onset Diabetes

Aim To identify predictors for individualization of antidiabetic therapy in patients with new onset T2DM. Research Design and Methods 261 drug naïve participants in the EDICT study, with new onset diabetes, were randomized in a single-center study to receive: (1) metformin followed by glipizide and then insulin glargine upon failure to achieve HbA1c <6.5%, or (2) initial triple therapy with metformin/pioglitazone/ exenatide. Each patient received 75-gram OGTT prior to start of therapy. Factors that predicted response to therapy were identified using the aROC method. Results 39 patients started and maintained the treatment goal (HbA1c <6.5%) on metformin only, and did not require intensification of antihyperglycemic therapy; 54 patients required addition of glipizide to metformin; and 47 patients required insulin addition to metformin plus glipizide for glucose control. The C-Pep120/C-Pep0 ratio during the OGTT was the strongest predictor of response to therapy. Patients with ratio <1.78 were more likely to require insulin for glucose control, while patients with ratio >2.65 were more likely to achieve glucose control with metformin monotherapy. In patients started on initial Triple Therapy the HbA1c decreased independent of C-Pep120/C-Pep0 ratio. Conclusion The increase in plasma C-peptide concentration above fasting following glucose load predicts the response to antihyperglycemic therapy in patients with new onset diabetes. C-Pep120/C-Pep0 provides a useful tool for individualization of antihyperglycemic therapy in patients with new onset diabetes.

Importance of blood glucose self-monitoring in treatment of diabetes mellitus in the modern world

Diabetes mellitus is a chronic disorder associated with microvasular and macrovascular complications, the prevention of which is an important challenge of modern medicine. Contemporary methods for diabetes management rely on the active involvement of the patient. Self-monitoring of blood glucose (SMBG) provides the basis for efficient antihyperglycemic therapy and prevention of hypoglycemia, as well as for the improvement of patient adherence to treatment. The importance of SMBG has further increased during the COVID-19 pandemic, since the adequate glycemic control can reduce the risk of COVID-19 infection and the disease severity in patients with DM. The recommended frequency of SMBG in patients with DM is discussed. A variety of glucose meters are available for measurement of blood glucose. Compliance with accuracy standards, simplicity and convenience for patients are the important criteria for selecting the glucose meter.

Evaluation of the prognostic significance of leptin, adiponectin and resistin in the development of diabetic retinopathy in type 2 diabetes mellitus patients

Background. There is evidence of the participation of adipose tissue hormones leptin, adiponectin and resistin in the formation of metabolic disorders in the retina, retinal neovascularization, and diabetic microangiopathy. The development of methods for the mathematical evaluation of the prognosis of diabetic retinopathy (DR) formation with the participation of adipokines is a relevant problem in modern diabetology. Aim. Elaboration of a mathematical model for assessing the prognostic significance of serum leptin, adiponectin and resistin to study the likelihood of deve­loping and progressing DR in patients with type 2 diabetes mellitus (DM). Materials and methods. An open observational single-center one-stage selective study was conducted among patients with type 2 DM and DR. The blood serum concentration of leptin, adiponectin and resistin, HbA1с, lipid metabolism findings were determined, the results of an instrumental examination of the fundus were analyzed. The diagnostic predictive value of serum leptin, adiponectin and resistin was assessed using discriminant analysis. Statistical analyses were conducted using Statistica 9.0 (StatSoft, Tulsa, OK, USA) software. The differences were considered statistically signifi­cant at p < 0.05. A model with linear combinations of the serum leptin, adiponectin and resistin, triglyceride (TG), HbA1с, type of antihyperglycemic therapy (oral anti-hyperglycemic medication or insulin therapy) were developed, and, subsequently, formulas for classification-relevant discriminant functions were derived. Results. Fifty-nine patients (107 eyes) with type 2 DM and DR (men and women; mean age, 58.20 ± 0.18 years; mean diabetes duration, 9.19 ± 0.46 years; mean HbA1с 9.10 ± 0.17 %) were assigned to the basic group and underwent the study. They were divided into three DR groups based on the stage of DR. When performing the ran­king of patients for discriminant analysis, the stage 2 DR group was aggregated with the stage 3 DR group for convenience to form the stage 2 + 3 DR group based on the pathognomonic sign (portents of proliferation or actual proliferation). Anti-diabetic therapy (ADT) included metformin, either alone (type 1 ADT) or in combination with oral anti-hyperglycemic medication (metformin + OAHGM, type 2 ADT) or insulin therapy (metformin + IT, type 3 ADT). Inclusion criteria were informed consent, age above 18 years, pre­sence of T2DM and DR. Exclusion criteria were endocrine or body system disorders leading to obesity (Cushing’s syndrome, hypothyroidism, hypogonadism, polycystic ovarian syndrome, or other endocrine disorders, including hereditary disorders, and hypothalamic obesity), type 1 DM, acute infectious disorders, history of or current cancer, decompensation of comorbidities, mental disorders, treatment with neuroleptics or antidepressants, proteinuria, clinically significant maculopathy, glaucoma or cataract. The study followed the ethical standards stated in the Declaration of Helsinki and was approved by the Local Ethics Committee. The formulas for classification-relevant discriminant functions were derived based on the results of physical examination, imaging and laboratory tests, and subsequent assessment of clinical signs of DM (HbA1с), DR stage and serum leptin, adiponectin, resistin, TG concentrations and taking into account the type of antihyperglycemic therapy. The classification functions (CF) computed based on the variables found from the above developed models provided the basis for predicting the development of DR. The formulas for CF from model are as follows: CF1 = 0.29 • TG + 1.55 • HbA1С + 1.81 • ADT_Type + 0.04 • Leptin + 0,34 • Adiponectin + 0,91 • Resistin – 13,82. CF2= 0.05 • TG + 1.36 • HbA1С + 3.01 • ADT_Type + 0.08 • Leptin + 0,35 • Adiponectin + 1,01 • Resistin – 15.95. A step-by-step approach to a diagnostic decision should be used. First, blood samples are tested for serum leptin, adiponectin and resistin, TG, blood HbA1c, and the patient is assigned a code for ADT Type (metformin only, 1; metformin + OAHGM, 2; or metformin + IT, 3). Second, CF1 and CF2 values are calculated based on clinical and laboratory data. Finally, the two values are compared to determine which is greater. The predictive decision is made by selecting the classification function with the greater value. Thus, if CF1 > CF2, the process can be stabilized at this stage given adequate glycemic control (through compensation of carbohydrate metabolism) and body mass control as well as patient compliance. If CF1 < CF2, the pathological process may progress to the next stage or even within stage 3, and there is an urgent need to reduce BMI, and to correct the ADT and the blood lipid profile. Conclusions. The informative value and statistical significance of the model were 71.4 % and p = 0.040, respectively. Using the formulas, one can determine the probability of progression of DR.