Tissue and Circulating MicroRNAs 378 and 142 as Biomarkers of Obesity and Its Treatment Response.

Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation.

Incoherent optical fluctuation flowmetry for detecting limbs with hemodynamically significant stenoses in patients with type 2 diabetes.

INTRODUCTION: The development of new highly accurate, inexpensive and accessible methods for the detection of lower-extremity peripheral artery disease (LE-PAD) in diabetic patients is required. The aim of this study was to evaluate the accuracy of a new incoherent optical fluctuation flowmetry (IOFF) method in detecting legs with hemodynamically significant stenoses compared to ankle brachial index (ABI) and transcutaneous oximetry (TcPO2) in patients with diabetes mellitus (DM). MATERIALS AND METHODS: Patients were recruited into 2 groups. Group 1 included patients with DM without LE-PAD and/or diabetic foot syndrome; Group 2 included patients with DM and LE-PAD. All patients underwent the following measurements: ultrasound (reference method), ABI, TcPO2, and the new IOFF method. RESULTS: The new IOFF method showed a sensitivity of 79.5% and a specificity of 89.8% in detecting limbs with hemodynamically significant stenosis (AUC 0.890, CI 0.822-0.957). TcpO2 allows the diagnosis of LE-PAD with 69.2% sensitivity and 86.2% specificity (AUC 0.817, CI 0.723-0.911). Using a standard ABI cut-off of less than 0.9, the sensitivity and specificity for this parameter were 34.5% and 89.7%, respectively. Increasing the diagnostic cut-off of the ABI on the study group to 0.99 improved sensitivity to 84.6% and specificity to 78% (AUC,0.824 CI 0.732-0.915). CONCLUSIONS: The new IOFF technique has demonstrated high sensitivity and specificity in the detection of LE-PAD in patients with DM. The high accuracy, rapid measurement, and potential availability suggest that the new IOFF method has a high potential for clinical application in the detection of PAD.

Predictors of Carbohydrate Metabolism Disorders and Lethal Outcome in Patients after Myocardial Infarction: A Place of Glucose Level.

BACKGROUND AND AIM: The aim of this study was to reveal statistical patterns in patients with acute myocardial infarction (AMI) that cause the development of carbohydrate metabolism disorders (CMD) (type 2 diabetes mellitus and prediabetes) and death within 5 years after AMI. METHODS: 1079 patients who were treated with AMI in the Almazov National Medical Research Center were retrospectively selected for the study. For each patient, all data from electronic medical records were downloaded. Statistical patterns that determine the development of CMDs and death within 5 years after AMI were identified. To create and train the models used in this study, the classic methods of Data Mining, Data Exploratory Analysis, and Machine Learning were used. RESULTS: The main predictors of mortality within 5 years after AMI were advanced age, low relative level of lymphocytes, circumflex artery lesion, and glucose level. Main predictors of CMDs were low basophils, high neutrophils, high platelet distribution width, and high blood glucose level. High values of age and glucose together were relatively independent predictors. With glucose level >11 mmol/L and age >70 years, the 5-year risk of death is about 40% and it rises with increasing glucose levels. CONCLUSION: The obtained results make it possible to predict the development of CMDs and death based on simple parameters that are easily available in clinical practice. Glucose level measured on the 1st day of AMI was among the most important predictors of CMDs and death.

Incoherent Optical Fluctuation Flowmetry: A New Method for the Assessment of Foot Perfusion in Patients with Diabetes-Related Lower-Extremity Complications.

(1) Background: To date, there are no studies evaluating the ability of the incoherent optical fluctuation flowmetry (IOFF) method to assess foot tissue perfusion. The aim of this study was to evaluate the correlation between perfusion values measured by IOFF and TcPO2 in patients with diabetes-related lower-extremity complications. (2) Methods: This was an observational, cross-sectional, two-center study. Diabetic patients with peripheral artery disease and/or diabetic foot ulcers were studied (n = 27, examinations were carried out on 54 legs). Perfusion in the foot tissues was assessed using TcPO2 (reference standard for this study) and the IOFF method. (3) Results: High correlation coefficients of all perfusion parameters measured by IOFF with TcPO2 (Rs 0.7 to 0.76) were shown. The study demonstrated that the IOFF method allows, with a sensitivity of 85.7% and a specificity of 90.0%, the identification of patients with a critical decrease in TcPO2 < 20 mmHg. (4) Conclusions: The high correlation of IOFF parameters with TcPO2 and the moderately high sensitivity and specificity in detecting patients with severe ischemia of foot tissues shows the promise of the method for assessing a tissue perfusion in patients with diabetes-related lower-extremity complications.

Simple Predictors for Cardiac Fibrosis in Patients with Type 2 Diabetes Mellitus: The Role of Circulating Biomarkers and Pulse Wave Velocity.

Cardiac fibrosis is the basis of structural and functional disorders in patients with diabetes mellitus (T2DM). A wide range of laboratory and instrumental methods is used for its prediction. The study aimed to identify simple predictors of cardiac fibrosis in patients with T2DM based on the analysis of circulating fibrosis biomarkers and arterial stiffness. The study included patients with T2DM (n = 37) and cardiovascular risk factors (RF, n = 27) who underwent ECHO, cardiac magnetic resonance imaging (MRI), pulse wave analysis (PWV), reactive hyperemia (RH), peripheral arterial tonometry, carotid ultrasonography, and assessment of serum fibrosis biomarkers. As a control group, 15 healthy subjects were examined. Left ventricular concentric hypertrophy was accompanied by an increased serum galectin-3 level in T2DM patients. There was a relationship between the PICP and HbA1c levels in both main groups (R2 = 0.309; p = 0.014). A negative correlation between PICP level and the global longitudinal strain (GLS) was found (r = −0.467; p = 0.004). The RH index had a negative correlation with the duration of diabetes (r = −0.356; p = 0.03), the carotid-femoral PWV (r = −0.371; p = 0.024), and the carotid intima-media thickness (r = −0.622; p < 0.001). The late gadolinium-enhanced (LGE) cardiac MRI was detected in 22 (59.5%) T2DM and in 4 (14.85%) RF patients. Diabetes, its baseline treatment with metformin, HbA1c and serum TIMP-1 levels, and left ventricle hypertrophy had moderate positive correlations with LGE findings (p < 0.05). Using the multivariate regression analysis, increased TIMP-1 level was identified as an independent factor associated with cardiac fibrosis.

Relationship between the Levels of lncRNA H19 in Plasma and Different Adipose Tissue Depots with Patients' Response to Bariatric Surgery.

Bariatric surgery represents a widespread approach to treating morbid obesity. The search for biomarkers to identify patients to whom this type of treatment will be most effective is needed. Our aim was to characterize the relationship of levels of lncRNA H19 in plasma and different adipose tissue depots with patients' response to bariatric surgery. The study includes control subjects, patients with obesity and patients with obesity accompanied by impaired carbohydrate metabolism (ICM). Quantitative analysis of lncRNA H19 levels has been performed using qPCR in plasma and subcutaneous (SAT) and visceral adipose tissue (VAT). Patients with obesity without ICM have higher levels of lncRNA H19 in VAT compared to SAT, and higher levels of lncRNA H19 in SAT compared to SAT of control individuals. One year after the intervention, levels of lncRNA H19 decreased in SAT of patients with obesity without ICM. The preoperative level of lncRNA H19 in VAT demonstrates a positive correlation with excess weight loss and a negative correlation with initial BMI. In conclusion, ICM affects expression of lncRNA H19 in SAT of patients with obesity. The preoperative level of lncRNA H19 in VAT can be used to predict excess weight loss in patients with obesity after bariatric surgery.

Prediction scale of response to liraglutide therapy as the method for increase of treatment efficacy in type 2 diabetes.

BACKGROUND: The effects of liraglutide on body weight and hemoglobin A1C (HbA1c) level vary greatly. The cost of this drug negatively affects treatment adherence. AIM: To reveal the baseline patient characteristics, associated with a better response to liraglutide. MATERIALS AND METHODS: A total of 41 patients with BMI of 39.63 ± 7.59 kg/m2 who received liraglutide injection up to 1.8 or 3.0 mg/day for 6 months were enrolled. Demographic and anthropometric data, parameters of glycemic control, food intake, hormones and responses to the eating behavior questionnaire were collected. RESULTS: Weight reduction was dose-dependent (p = 0.007). Liraglutide was not effective in patients with BMI >45 kg/m2. The baseline HbA1c level was a significant factor for HbA1c reduction. Lower leptin and higher glucagon-like-peptide 1 concentrations might predict better weight loss response to liraglutide. CONCLUSION: Drug-specific efficacy predictors were assumed; thus, further studies are needed to prove their significance.

Metformin: Expanding the Scope of Application-Starting Earlier than Yesterday, Canceling Later.

Today the area of application of metformin is expanding, and a wealth of data point to its benefits in people without carbohydrate metabolism disorders. Already in the population of people leading an unhealthy lifestyle, before the formation of obesity and prediabetes metformin smooths out the adverse effects of a high-fat diet. Being prescribed at this stage, metformin will probably be able to, if not prevent, then significantly reduce the progression of all subsequent metabolic changes. To a large extent, this review will discuss the proofs of the evidence for this. Another recent important change is a removal of a number of restrictions on its use in patients with heart failure, acute coronary syndrome and chronic kidney disease. We will discuss the reasons for these changes and present a new perspective on the role of increasing lactate in metformin therapy.

Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05). Gal - 3 > 10 ng/ml (OR = 2.25; 95% CI, 1.88-5.66; p = 0.01) and NT - pro - BNP > 80 pg/ml (OR = 2.64; 95% CI, 1.56-4.44; p = 0.001) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

Prediction model for thyrotoxic atrial fibrillation: a retrospective study.

BACKGROUND: Thyrotoxic atrial fibrillation (TAF) is a recognized significant complication of hyperthyroidism. Early identification of the individuals predisposed to TAF would improve thyrotoxic patients' management. However, to our knowledge, an instrument that establishes an individual risk of the condition is unavailable. Therefore, the aim of this study is to build a TAF prediction model and rank TAF predictors in order of importance using machine learning techniques. METHODS: In this retrospective study, we have investigated 36 demographic and clinical features for 420 patients with overt hyperthyroidism, 30% of which had TAF. At first, the association of these features with TAF was evaluated by classical statistical methods. Then, we developed several TAF prediction models with eight different machine learning classifiers and compared them by performance metrics. The models included ten features that were selected based on their clinical effectuality and importance for model output. Finally, we ranked TAF predictors, elicited from the optimal final model, by the machine learning tehniques. RESULTS: The best performance metrics prediction model was built with the extreme gradient boosting classifier. It had the reasonable accuracy of 84% and AUROC of 0.89 on the test set. The model confirmed such well-known TAF risk factors as age, sex, hyperthyroidism duration, heart rate and some concomitant cardiovascular diseases (arterial hypertension and conjestive heart rate). We also identified premature atrial contraction and premature ventricular contraction as new TAF predictors. The top five TAF predictors, elicited from the model, included (in order of importance) PAC, PVC, hyperthyroidism duration, heart rate during hyperthyroidism and age. CONCLUSIONS: We developed a machine learning model for TAF prediction. It seems to be the first available analytical tool for TAF risk assessment. In addition, we defined five most important TAF predictors, including premature atrial contraction and premature ventricular contraction as the new ones. These results have contributed to TAF prediction investigation and may serve as a basis for further research focused on TAF prediction improvement and facilitation of thyrotoxic patients' management.

Regulatory Action of Plasma from Patients with Obesity and Diabetes towards Muscle Cells Differentiation and Bioenergetics Revealed by the C2C12 Cell Model and MicroRNA Analysis.

Obesity and type 2 diabetes mellitus (T2DM) are often combined and pathologically affect many tissues due to changes in circulating bioactive molecules. In this work, we evaluated the effect of blood plasma from obese (OB) patients or from obese patients comorbid with diabetes (OBD) on skeletal muscle function and metabolic state. We employed the mouse myoblasts C2C12 differentiation model to test the regulatory effect of plasma exposure at several levels: (1) cell morphology; (2) functional activity of mitochondria; (3) expression levels of several mitochondria regulators, i.e., Atgl, Pgc1b, and miR-378a-3p. Existing databases were used to computationally predict and analyze mir-378a-3p potential targets. We show that short-term exposure to OB or OBD patients' plasma is sufficient to affect C2C12 properties. In fact, the expression of genes that regulate skeletal muscle differentiation and growth was downregulated in both OB- and OBD-treated cells, maximal mitochondrial respiration rate was downregulated in the OBD group, while in the OB group, a metabolic switch to glycolysis was detected. These alterations correlated with a decrease in ATGL and Pgc1b expression in the OB group and with an increase of miR-378a-3p levels in the OBD group.

Terahertz spectroscopy of diabetic and non-diabetic human blood plasma pellets.

SIGNIFICANCE: The creation of fundamentally new approaches to storing various biomaterial and estimation parameters, without irreversible loss of any biomaterial, is a pressing challenge in clinical practice. We present a technology for studying samples of diabetic and non-diabetic human blood plasma in the terahertz (THz) frequency range. AIM: The main idea of our study is to propose a method for diagnosis and storing the samples of diabetic and non-diabetic human blood plasma and to study these samples in the THz frequency range. APPROACH: Venous blood from patients with type 2 diabetes mellitus and conditionally healthy participants was collected. To limit the impact of water in the THz spectra, lyophilization of liquid samples and their pressing into a pellet were performed. These pellets were analyzed using THz time-domain spectroscopy. The differentiation between the THz spectral data was conducted using multivariate statistics to classify non-diabetic and diabetic groups' spectra. RESULTS: We present the density-normalized absorption and refractive index for diabetic and non-diabetic pellets in the range 0.2 to 1.4 THz. Over the entire THz frequency range, the normalized index of refraction of diabetes pellets exceeds this indicator of non-diabetic pellet on average by 9% to 12%. The non-diabetic and diabetic groups of the THz spectra are spatially separated in the principal component space. CONCLUSION: We illustrate the potential ability in clinical medicine to construct a predictive rule by supervised learning algorithms after collecting enough experimental data.

[Peculiarity of recovery of the hypothalamic-pituitary-gonadal (hpg) axis, in men after using androgenic anabolic steroids].

BACKGROUND: Spontaneous recovery of the hypothalamic–pituitary–gonadal (HPG) axis after cessation of testosterone replacement therapy or after male contraception may take up to 24 months. There is insufficient data on the duration of recovery of HPG axis after abuse of androgenic anabolic steroids (AAS). AAS users use post-cycle therapy (PCT) to restore HPG axis, the effectiveness of which is unknown and needs further investigation. AIMS: To evaluate the recovery of HPG axis in men, AAS users, after a 3-month of cessation of their use and after PCT. METHODS: An observational, single-center, prospective, sampling, open, uncontrolled study was conducted among male AAS users. While using of AAS and 3 months after the refusal of their administration and PCT, the clinical symptoms of hypogonadism were evaluated, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (Tt), prolactin, estradiol, inhibin B, thyroid-stimulating hormone (TSH) were determined. The scheme of rehabilitation therapy was the same and did not change throughout the study. Recovery criteria: Tt >3.4 ng/ml and LH >1.24 mIU/ml. The study was conducted from January to August 2019. Fisher’s exact test, Mann-Whitney U-test, and Spearman’s rank correlation coefficient were used. The differences were considered statistically significant at p<0.05. RESULTS: The study included 44 men, their age 29 years [27.75; 34], the duration of the use of AAS is 6 months [3.52; 7]. During the use of AAS: LH 0.2 mIU/ml [0.04; 0.47], Tt — 4.34 ng/ml [1.05; 8.81]. In this group, the number of men with a LH level <1.24 mIU / ml was 84% (n=37) and Tt <3.4 ng/ml was 47.7% (n=21). After 3 months, the LH level reached 4.12 mIU/ml [2.58; 5.84], Tt — 4.55 ng/ml [3.76; 6.24]. At the same time, the level of Tt <3.4 ng/ml remained in 20.5% (n=9), and LH <1.24 mIU/ml in 4.5% (n=2) men. According to the level of recovery of LH and Tt, patients were divided into two groups: with satisfying (n=35; 79.5%) and poor (n=9; 20.5%) recovery. A clear correlation was established between the duration of use (-0.857; p<0.0001), the amount (-0.443; p=0.003), the dose (-0.7825; p<0.0001), the type of AAS (-0.698; p<0.0001) and testosterone level recovery. A correlation between inhibin B and Tt (0.418; p=0.005) was revealed. CONCLUSIONS: A three-month refusal to use AAS with PCT led to the restoration of HPG axis a in 79.5% of the volunteers. In 20.5% of cases, recovery did not occur. The negative effect of the duration of use, the number of simultaneously administered drugs, their dose and type of AAS on the restoration of HPG axis was established. The level of inhibin B may serve as a marker for the restoration of spermatogenic epithelium.

A new perspective on bronchial asthma and chronic obstructive pulmonary disease overlap: potential diagnostic criteria.

OBJECTIVE: The aim: The aim of the research was to analyze the results of observation andexamination of COPD patients in order to identify a group of individualswith potentialasthma overlap. PATIENTS AND METHODS: Materials and methods:We have conducted a two-stagedynamic investigation of 43 COPD patients during 3-8 years. The patients were divided into two groups: group 1 counted 30 individuals who presented with at least one episode of reversible bronchial obstruction (RBO) during the observation; group 2 - 13 individuals who presented with nonreversible bronchial obstruction (nonRBO). At the first stage, we conducted a clinical observations analysis and studied lung function examination records; at the second stage, we calculated the markers of allergic inflammation. RESULTS: Results: It was revealed that around 70% of COPD patients have occasional episodes of RBO. It was established that the level of blood eosinophils in these patients on the whole is rather low even in people with intermittent RBO, and the total IgE level appeared to be significantly higher in patients with intermittent RBO comparing to the level of this marker in patients who have nonRBO. CONCLUSION: Conclusions:COPD patients with intermittent RBO and high level of total IgE level form a group with potential asthma overlap.

Short-term renal and metabolic effects of low dose vildagliptin treatment added-on insulin therapy in non-proteinuric patients with type 2 diabetes: open-label randomized prospective study

ABSTRACT Objective The aim of this randomized comparative study was to assess renal and metabolic effects of vildagliptin in insulin-treated type 2 diabetes (T2DM) patients without overt chronic kidney disease. Subjects and methods We randomized 47 insulin-treated non-proteinuric patients with satisfactory controlled T2DM and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 either to continue insulin therapy (control) or to receive combined insulin-vildagliptin treatment (VIG group). We assessed eGFR using serum creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys), and urinary creatinine-adjusted excretion of albumin (UACR), type IV collagen (uCol IV/Cr), and neutrophil gelatinase-associated lipocalin (uNGAL/Cr) at baseline and after 6 months of treatment. Results Study groups were comparable in terms of age and sex (60.1 ± 6.1 years and 42.9% men in control group vs. 60.8 ± 5.2 years and 39.1% in VIG group). After 6 months of treatment, there were no significant changes in main assessed parameters in control group. VIG group demonstrated significant decrease in HbA1c, diastolic blood pressure, frequency of hypoglycemia, and high-sensitivity C-reactive protein level as compared to the changes in control group. While eGFRcreat, UACR, and uNGAL/Cr showed no significant changes after vildagliptin addition, eGFRcys, eGFRcreat-cys, and uCol IV/Cr changed significantly in comparison with control group (+7.0% [3.7;13.3]; +5.1% [1.4;8.5]; -32,8% [-55.8;-24.4], respectively, p < 0.01 each). Correlation and regression analysis revealed glucose-independent pattern of these changes. Conclusion Addition of vildagliptin to ongoing insulin therapy in patients with T2DM was associated with a reduction in uCol IV/Cr and an increase in eGFRcys and eGFRcreat-cys, independent of T2DM control parameters.

Short-term renal and metabolic effects of low dose vildagliptin treatment added-on insulin therapy in non-proteinuric patients with type 2 diabetes: open-label randomized prospective study.

Objective The aim of this randomized comparative study was to assess renal and metabolic effects of vildagliptin in insulin-treated type 2 diabetes (T2DM) patients without overt chronic kidney disease. Subjects and methods We randomized 47 insulin-treated non-proteinuric patients with satisfactory controlled T2DM and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 either to continue insulin therapy (control) or to receive combined insulin-vildagliptin treatment (VIG group). We assessed eGFR using serum creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys), and urinary creatinine-adjusted excretion of albumin (UACR), type IV collagen (uCol IV/Cr), and neutrophil gelatinase-associated lipocalin (uNGAL/Cr) at baseline and after 6 months of treatment. Results Study groups were comparable in terms of age and sex (60.1 ± 6.1 years and 42.9% men in control group vs. 60.8 ± 5.2 years and 39.1% in VIG group). After 6 months of treatment, there were no significant changes in main assessed parameters in control group. VIG group demonstrated significant decrease in HbA1c, diastolic blood pressure, frequency of hypoglycemia, and high-sensitivity C-reactive protein level as compared to the changes in control group. While eGFRcreat, UACR, and uNGAL/Cr showed no significant changes after vildagliptin addition, eGFRcys, eGFRcreat-cys, and uCol IV/Cr changed significantly in comparison with control group (+7.0% [3.7;13.3]; +5.1% [1.4;8.5]; -32,8% [-55.8;-24.4], respectively, p < 0.01 each). Correlation and regression analysis revealed glucose-independent pattern of these changes. Conclusion Addition of vildagliptin to ongoing insulin therapy in patients with T2DM was associated with a reduction in uCol IV/Cr and an increase in eGFRcys and eGFRcreat-cys, independent of T2DM control parameters.

Frequent ventricular extrasystoles after heart transplantation: a late presentation of amiodarone-induced thyrotoxicosis: a case report.

BACKGROUND: There is a lack of information about a mixed type of amiodarone-induced thyrotoxicosis (AIT) after heart transplantation (HTx) with no amiodarone treatment in almost 1 year. Frequent ventricular extrasystoles (VES) associated with a mixed type of AIT can often be treated using thiamazole and prednisolone, without the need for specific antiarrhythmic treatment. CASE SUMMARY: We present a clinical case of a 65-year-old heart transplanted male patient with frequent VES associated with mixed type of AIT. Recipient had managed with amiodarone prior to HTx but there were no indications for it after the surgery. One year after antiarrhythmic treatment was discontinued, monomorphic VES (total amount: 27 472/day) were diagnosed. In addition, our investigation revealed that thyrotoxicosis developed. Prednisolone and thiamazole were added to the treatment with positive outcomes. The antithyroid treatment had been discontinued after 9 months and results of the 24-h Holter electrocardiogram monitoring showed only two VES/24 h. DISCUSSION: The case highlights the association of amiodarone, thyroid disorders, and VES. In mixed type AIT or if diagnosis is uncertain, it is reasonable to use mixed therapy. Next is to decide whether you need special treatment for VES. There was no evidence of ventricular tachycardia. Thyroid function tests remained normal off antithyroid medications and the total amount of VES significantly decreased. There were no indications for any antiarrhythmic treatment or ablation.

Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity.

RATIONALE: It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. PURPOSE: To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. METHODS: The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients' evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. RESULTS: Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss ≥ 5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. CONCLUSION: The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.

Mental state, psychoemotional status, quality of life and treatment compliance in patients with Type 2 diabetes mellitus.

AIM: To identify correlations between quality of life (QoL), emotional and mental state in patients with Type 2 diabetes mellitus (T2DM) and to evaluate its contribution in prediction of compliance. MATERIALS & METHODS: The T2DM patients aged 18-75 years with at least 12 weeks of stable hypoglycemic therapy were included to this cross-sectional study. We used Mini Mental State Examination (MMSE) for mental state assessment, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression level and EQ-5D for QoL. Compliance level was self-reported by patients. RESULTS: The QoL positively correlates with MMSE score (p < 0.0001) and negatively with HADS anxiety (p < 0.0001) and depression (p < 0.0001) levels. The MMSE score is higher (p < 0.0001), and both HADS levels are lower (p < 0.01) in patients with higher compliance level. CONCLUSION: Cognitive function and psychoemotional state in T2DM patients are important for treatment compliance and QoL and are to be corrected whenever possible.

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus.

AIM: To evaluate the effects of glucagon-like peptide-1 analogs (GLP-1a) combined with insulin on myocardial ischemia-reperfusion injury in diabetic rats. METHODS: Type 2 diabetes mellitus (T2DM) was induced in male Wistar rats with streptozotocin (65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows: (1) control rats; (2) insulin (0.1 U/kg) treated rats prior to ischemia; (3) insulin (0.1 U/kg) treated rats at reperfusion; (4) GLP-1a (140 mg/kg) treated rats prior to ischemia; (5) GLP-1a (140 mg/kg) treated rats at reperfusion; and (6) rats treated with GLP-1a (140 mg/kg) prior to ischemia plus insulin (0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively. RESULTS: There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size (34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1a had no effect on infarct size. However, pre-ischemic administration of GLP-1a reduced infarct size to 12% ± 2.2% (P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1a prior to ischemia and insulin at reperfusion (8% ± 1.6%, P < 0.05 vs the control and GLP-1a alone treated groups). CONCLUSION: GLP-1a pre-administration results in myocardial infarct size reduction in rats with T2DM. These effects are maximal in rats treated with GLP-1a pre-ischemia plus insulin at reperfusion.