TYPE 2 DIABETES MELLITUS’S DECOMPENSATED FORM: ON THE PROBLEM OF EFFECTIVE PHARMACOTHERAPY IN REAL CLINICAL PRACTICE

The aim of this retrospective study was to analyze the pharmacotherapy regimens of the decompensated form of type 2 diabetes mellitus (DM2) and to evaluate its effectiveness, its compliance with clinical recommendations.Materials and methods: A retrospective analysis of 54 medical cards of patients with decompensated DM2 was conducted. The 1st group (n=24; 44%) included the patients who had a decrease in glycated hemoglobin (HbA1c) by 50% or more in 3 months after hypoglycemic therapy; and the 2nd group (n=30; 56%) – the patients whose HbA1c level decreased by less than 50%.Results. A HbA1c level was 10.4% in the 1st group and 13.2% in the 2nd group (р<0.001). However, the target levels of venous blood plasma glucose and HbA1c were not achieved in any of the patient groups. The total number of the drugs prescribed to the patients ranged from 4 (in 25% (n=6) and 10% (n=3) cases in the 1st and the 2nd groups, respectively) to 8 (in 12.5% (n=3) and 20% (n=6) cases in the 1st and the 2nd, groups, respectively). However, in a number of cases some violations of clinical recommendations were recorded: the prescription to the obese patients of insulin drugs, the administration of sulfonylureas derivatives to patients with a history of cardiovascular diseases of the atherosclerotic origin, but modern hypoglycemic drugs with proven benefits in reducing cardiovascular risks were rarely prescribed.Conclusion. The tactics of pharmacotherapy in the patients with a decompensated form of DM2 does not fully comply with the approved clinical guidelines, which requires the effectiveness of treatment optimization of this medically and socially significant pathology.

Evaluation and treatment of peripheral nervous system dysfunction in patients with prediabetes

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

Retrospective analysis of clinical outcomes of patients with COVID-19 depending on receiving antihypertensive, lipid-lowering and antihypertensive therapy

Background. The main factors that increase the risk of cardiovascular accidents and mortality among patients with COVID-19 include hyperglycemia, arterial hypertension and dyslipidemia. Therefore, all patients with COVID-19 and metabolic syndrome should receive antihypertensive (AHT), hypolipidemic (GLT) and hypoglycemic therapy (GGT). Currently, there is a limited number of studies regarding the effectiveness and safety of this therapy in patients with COVID-19. Aim. Evaluate the clinical outcomes of patients with COVID-19, depending on the recipient of AHT, GLT and GGT. Materials and methods. A retrospective analysis of the clinical outcomes "discharged/died" of 1753 patients with COVID-19 was carried out depending on the received AHT, GLT and GGT. Results. A significant reduction in the risk of mortality among patients with COVID-19 was observed during therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers ACE inhibitors/ARBs (OR 0.39, 95% CI 0.210.72; p0.05) and b-adrenergic blockers b-AB (OR 0.53, 95% CI 0.281; p0.05). At the same time, against the background of therapy with ACE inhibitors/ARBs and b-ABs, the chance of mortality decreased more significantly among patients with type 2 diabetes mellitus (T2DM) compared with patients without T2DM. Diuretic therapy was associated with a 3-fold increase in the chances of death: OR 3.33, 95% CI 1.884.79; p0.05. Statin therapy did not affect clinical outcomes in COVID-19 patients. On the background of therapy with oral hypoglycemic drugs, the risk of mortality decreased 5-fold (OR 0.19, 95% CI 0.070.54; p0.05). Against the background of insulin therapy, there was an increase in mortality risk by 2.8 times (OR 2.81, 95% CI 1.55.29; p0.05). Conclusion. A significant reduction in mortality among patients with COVID-19 was observed during therapy with ACEI/ARB, b-AB, and oral hypoglycemic therapy. Increased risk of death was associated with insulin therapy and diuretic therapy.

Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy

Objective. Significantly underdiagnosed, diabetes-associated cardiac autonomic neuropathy (CAN) causes a wide range of cardiac disorders that may cause life-threatening outcomes. This study investigated the effects of alpha-lipoic acid (ALA) on arterial stiffness and insulin resistance (IR) parameters in type 2 diabetes mellitus (T2D) patients and definite CAN. Methods. A total of 36 patients with T2D and a definite stage of CAN were recruited. This investigation was carried out on two separate arms: traditional hypoglycemic therapy (n=18, control) and ALA (n=18) 600 mg in film-coated tablets/q.d. in addition to traditional hypoglycemic therapy. The duration of the study was three months. Results. In subjects with T2D and definite stage of СAN, treatment with ALA resulted in a significant decrease of glucose, immunoreactive insulin concentration, and Homeostasis Model Assessment (HOMA)-IR (HOMA-IR) parameters; pulse wave velocity (PWV), aorta augmentation index (AIxao) during the active period of the day and decrease of PWV, AIxao, and brachial augmentation index during the passive period of the day compared with the results, obtained in the control group. Therefore, the administration of ALA to patients with T2D for three months promotes the improvement of glucose metabolism and arterial stiffness parameters. Conclusions. In patients with T2D and definite stage of СAN treatment with ALA improved HOMA-IR and arterial stiffness parameters. These findings can be of clinical significance for the complex treatment of diabetes-associated CAN.

DIABETES MELLITUS AND COVID-19. FEATURES OF THE MUTUAL INFLUENCE OF THE TWO PANDEMICS

Background.The COVID­19 pandemic that emerged in China in late 2019 continues to be a global public health problem. The growing incidence of diabetes mellitus makes it necessary to assess the mutual impact of these two diseases on the patient prognosis. Aim. The aim of the study was to review the current information about the effect of SARS­CoV­2 virus on the course of diabetes mellitus and mortality, to consider the probability of developing newly diagnosed diabetes mellitus in patients who underwent COVID­19, and to analyze the possibilities of hypoglycemic therapy in the treatment of COVID­19 diabetic disease. Material and methods.Literature sources were searched in the PubMed database, using the keywords: COVID­19, SARS­CoV­2, and diabetes mellitus. The analysis included literature reviews, meta­analyses, systematic reviews, and clinical trials. Results and discussion.After reviewing about 9,000 sources of literature, 295 of the most relevant publications were analyzed, 60 of which were included in this paper. Insufficiently controlled diabetes mellitus appears to be independently associated with COVID­19 severity and high risk of death. Patients with severe COVID­19 in the background of diabetes mellitus are more susceptible to the damaging effects of the cytokine storm. Against the background of SARS­CoV­2 infection joining diabetes mellitus, decompensation of the disease with hyperglycemia occurs, which is difficult to correct even with insulin therapy. SARS­CoV­2 virus has the ability to bind to angiotensin­converting enzyme type 2 receptors that are expressed in β­cells, which can lead to rapid metabolic deterioration with the development of diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. There is a hypothesis of a potential link between SARS­CoV­2 infection and the development of newly diagnosed diabetes through a direct effect of the virus on pancreatic β­cells. Certain blood glucose­lowering drugs can be continued when infected with SARS­CoV­2 with a positive effect. Conclusions. More research is needed to determine the role of SARS­CoV­2 virus in the development of acute complications and manifestation of diabetes mellitus. Possibilities of modern hypoglycemic therapy of diabetes in COVID­19 are generally evaluated positively and require further study.

Potential overtreatment of type 2 diabetes therapy in real clinical practice: Omsk Oblast register data

Backgraund: The total number of patients with type 2 diabetes mellitus (T2DM) in the Russian Federation as of 01.01.2019 is 4.24 million. The majority of patients with T2DM are elderly people and older, forming groups with high comorbidity and the risk of severe hypoglycemia, including those associated with excess hypoglycemic therapy. Foreign studies indicate that a significant proportion of older adults with diabetes are potentially exposed to excessive sugar-lowering therapy.Aims: to study the frequency of excessive decrease in HbA1c in a group of patients with T2DM according to a sample from the regional diabetes register.Materials and methods: A content analysis of the regional register of diabetes mellitus was carried out as of ­December 31, 2019. Based on the register data, an individual target level of HbA1c was calculated and the compliance of the achieved HbA1c level with the target level was assessed.Results: The analysis included data from 1202 patients with T2DM, which amounted to 2.35% of the total number of patients with T2DM in the region (n = 51,163). The age of the included individuals was 66 years (LQ 60.0; UQ 72), 360 men (29.95%). The duration of T2DM 8.0 years. The HbA1c level in the general group was 7.1%. Persons over 60 years of age accounted for 75.21% (n = 904). When analyzing HbA1c in the age groups, there were no statistically significant differences (p> 0.05). HbA1c was above the target level in 43.34% of cases (n = 521). The level of HbA1c <6.5% was noted in a quarter of cases (24.62%), including HbA1c <6.0% was recorded in 97 cases, which accounted for a third of all cases of tight glycemic control. At the same time, the majority of observations of HbA1c <6.5% were in patients 60 years and older (79.73%). Among young and middle-aged patients with HbA1c <6.5%, 8.33% of cases had risk factors for severe hypoglycemia in the presence of SU and / or insulin therapy. In the older age group (in comparison with young and middle-aged patients), HbA1c <7% (p <0.05) was significantly more often detected, there was a tendency for a higher frequency of HbA1c <6.5% (p = 0.067). Among elderly and senile patients with HbA1c <6.5%, in 41.53% of cases there were risk factors for severe hypoglycemia, in a quarter of cases in T2DM therapy SU and / or insulin were used (24.58%), almost every fifth patient (19.07%), risk factors for severe hypoglycemia, received SU and / or insulin.Conclusion: According to our data, at least a quarter of patients in the older age group (24.58%) had overtreatment and need de-intensification of therapy. Perhaps that in this group of patients, the risks associated with treatment may outweigh the benefits of tight glycemic control, and these patients require planned de-intensification of glucose-lowering therapy. Taking into account the position of some expert communities on determining the target range of HbA1c in the older age group, the need for de-intensification of antihyperglycaemic therapy may be even higher. Further research is required in order to develop a full-fledged domestic concept of de-intensification of hypoglycemic therapy.

Biomarkers of Glyco-Metabolic Control in Hemodialysis Patients: Glycated Hemoglobin vs. Glycated Albumin

Background and Objectives: Glycated hemoglobin (HbA1c) dosage is considered the gold standard in glycol-metabolic monitoring, but it presents limits, which can underestimate the glycemia trend. In this regard, it was introduced the glycated albumin (GA). The aim of the study is to verify the predictivity of the GA compared to HbA1c in identifying glyco-metabolic alterations in non-diabetic and diabetic hemodialysis (HD) patients. Materials and Methods: For this purpose, we conducted a multicenter study involving one analysis laboratory and six dialysis centers in the Lazio region (Rome, Italy). Both diabetic and non-diabetic HD patients represent the study population, and the protocol included five time points. Results: The analyzed data highlighted the ability of GA to predict changes in glycemic metabolism in HD patients, and GA values are not significantly influenced, like HbA1c, by dialysis therapy itself and by comorbidities of the uremic state, such as normochromic and normocytic anemia. Thus, GA seems to reflect early glyco-metabolic alterations, both in patients with a previous diagnosis of diabetes and in subjects without diabetes mellitus. As part of this study, we analyzed two HD patients (one diabetic and one non-diabetic) in which GA was more predictive of glycol-metabolic alterations compared to HbA1c. Our study confirms the need to compare classical biomarkers used for the monitoring of glyco-metabolic alterations with new ones, likely more reliable and effective in specific subgroups of patients in which the classic biomarkers can be influenced by the preexisting pathological conditions. Conclusions: In conclusion, our evidence highlights that in uremic patients, GA shows a better ability to predict glyco-metabolic alterations allowing both an earlier diagnosis of DM and a prompt modulation of the hypoglycemic therapy, thus improving the clinical management of these patients.

GLYCOSYLATED HEMOGLOBIN IN THE DIAGNOSIS AND CONTROL OF TYPE II DIABETES MELLITUS

Сахарный диабет характеризуется нарушением секреции инсулина и той или иной степенью инсулинорезистентности, обусловливающими гипергликемию. Диабет в 2 раза повышает риски появления широкого спектра сердечно-сосудистых заболеваний, в 6 раз повышает риски ИБС. ХБП развивается примерно у 35% пациентов с сахарным диабетом II типа и ассоциирован с повышенной смертностью. В Казахстане исследования на эту тему проведены не были. Уровень гликозилированного гемоглобина отражает состояние компенсации углеводного обмена, показывает эффективность сахароснижающей терапии и определяет стратегию лечения пациента. Diabetes mellitus is characterized by impaired insulin secretion and varying degrees of insulin resistance, causing hyperglycemia. Diabetes increases the risk of a wide range of cardiovascular diseases by 2 times, and increases the risk of CHD by 6 times. CKD develops in approximately 35% of patients with type II diabetes and is associated with increased mortality. No studies on this topic have been conducted in Kazakhstan. The level of glycosylated hemoglobin reflects the state of carbohydrate metabolism compensation, shows the effectiveness of hypoglycemic therapy and determines the patient's treatment strategy.

The diabetes mellitus and oncopathоlogy

The number of newly diagnosed cases of diabetes mellitus (DM) and various cancers is growing every year. Obviously, the presence of one disease significantly complicates the course of another. But it is still unclear whether diabetes potentiates the development of cancer or oncopathology will be the cause of carbohydrate metabolism disorders, and what effect the use of antidiabetic drugs has on the course of cancer.The purpose of this review was to establish a causal relationship between diabetes, hypoglycemic therapy and the development of oncopathology.Results. The hyperinsulinemia and hyperglycemia consistently increase the likelihood of tumor development not only in patients with diabetes but also in patients with prediabetes, and lead to some cancers, such as pancreatic, liver, stomach, colon, breast, kidney, lungs, etc. In addition, increasing or decreasing the risk of cancer may be a side effect of some antidiabetic drugs.Conclusions. Diabetes is a risk factor for cancer, especially hepatocellular, hepatobiliary, pancreatic, breast, ovarian, endometrial and gastrointestinal cancers. In general, treatment with sulfonylureas can increas the risk of cancer, while treatment associated with improved insulin resistance, such as metformin, may reduce this risk.It is obvious that many existing studies have ambiguous results and require correction due to organizational errors, ie it is necessary to conduct additional carefully planned and properly organized studies. In addition, given the importance of both diseases, we believe that diabetic patients need routine screening and orientation of medical personnel for early detection of oncopathology.