Vadim Valerievich Klimontov

BACKGROUND: Bariatric surgery is a highly effective method of type 2 diabetes (T2D) treatment in patients with morbid obesity, but surgical outcomes are variable: some patients do not achieve remission of T2D, others may have insufficient weight loss or subsequent weight regain. Existing models for predicting diabetes remission are not without limitations due to sample heterogeneity, differences in types of surgical interventions, and cohort sizes. Therefore, new prognostic models are needed. AIM: To determine predictors of T2D remission in patients with morbid obesity within a year after Mini-Gastric Bypass (MGB) or Single Anastomosis Sleeve Ileal Bypass (SASI). MATERIALS AND METHODS: A single-center retrospective study included 112 patients with T2D and morbid obesity who underwent either MGB ( n =86) or SASI ( n =26). The status of T2D remission was assessed for 12 months after surgery. Covariate-adjusted logistic regression, Cox regression analysis, and ROC analysis were used to analyze remission predictors. RESULTS: Remission of T2D within one year after surgery was achieved in 83 (74%) patients. No insulin therapy before surgery (OR=6.27, p 1c , OR=0.5, p p =0.023 and OR=1.21, p =0.041, respectively), and estimated glucose disposal rate (eGDR, OR=1.83, p =0.001) were predictors of remission in logistic regression analysis after adjustment for age, sex, body mass index, and type of operation. In Cox regression analysis, these factors, as well as diabetes duration and C-reactive protein (CRP) level, predicted faster onset of remission within the first year after surgery. The ROC analysis identified the following cut-off points of predictors: diabetes duration p =0.021); HbA _1c p 4 ng/mL ( p =0.003); postprandial C-peptide >6.5 ng/mL ( p 1.4 mg/kg/min ( p =0.043); CRP >6.4 mg/L ( p =0.045). A prognostic model based on the identified predictors was developed (AUC=0.92 [95% CI 0.82–0.99], overall accuracy=83% [95% CI 64–94%]). CONCLUSION: Achieving remission of T2D within one year after bariatric surgery (MGB, SASI) is associated with a shorter duration of T2D, absence of insulin therapy before surgery, lower preoperative HbA _1c levels, higher fasting and postprandial C-peptide levels, as well as higher preoperative insulin sensitivity (eGDR) and CRP levels.

It is well-known that the morbidity and clinical burden of type 2 diabetes mellitus (T2DM) are predominantly associated with its chronic complications, in which fibrosis is a significant contributor. Recently, sodium–glucose cotransporter 2 (SGLT2) inhibitors have made a pivotal advancement in the therapeutic landscape not only improving glycemic control, but also demonstrating high effectiveness in the prevention and treatment of T2DM complications. In this work, we aimed to assess the transcription factors (TFs) mediating the effects of SGLT2 inhibitor empagliflozin (EMPA) treatment by a comprehensive analysis of the allele-specific expression (ASE) events utilizing the RNA-seq data. Initial logistic regression analysis of the in vitro transcriptomic data for EMPA-treated peripheral blood mononuclear cells (PBMCs) of three healthy donors revealed a significant inter-individual variation in ASE for 240 genes linked to EMPA treatment beyond the glucose-lowering effects. Then, 146 TFs were predicted to regulate the expression of the corresponding targets using motifbreakR and DESeq2. Among these, multiple TFs (including ATF3, ATF4, E2F1, EGR1, FOS, JUN, JUNB, IRF8, KLF6, KLF11, SNAI1, TWIST1, and ZEB1) were involved in the TGF-β/SMAD3 canonical profibrotic signaling cascade, pertinent to diabetes-related fibrosis, playing a significant role in the development of diabetic complications. Further analysis of the in vivo data for the PBMCs from ten T2DM patients initiating EMPA therapy identified 98 TFs related to the ASE variation in both in vitro and in vivo cohorts. To conclude, our integrative allele-specific approach enables the prediction of novel EMPA-responsive regulatory interactions and suggests the important mediators of the mechanisms underlying the effects of EMPA on human PBMCs.

BACKGROUND: Bariatric surgery is the most effective treatment for morbid obesity and type 2 diabetes. Hypercortisolism in patients undergoing bariatric surgery may reduce the effectiveness of surgery and increase the risk of complications. AIM: To assess the prevalence and clinical forms of hypercortisolism in patients with morbid obesity and type 2 diabetes mellitus undergoing examination before bariatric interventions. MATERIALS AND METHODS: Screening for Cushing's syndrome was performed in patients with morbid obesity and type 2 diabetes mellitus referred to the clinic for examination before bariatric surgery. The overnight dexamethasone suppressive test with 1 mg dexamethasone (1-mg DST) was used as a first-line test. Additional tests included 24-hour urinary free cortisol excretion and evening cortisol level in saliva or blood serum. In case of pathological results of the second-line tests, the ACTH level was measured, and suppressive test with 8 mg dexamethasone was performed. RESULTS: The study included 91 patients, 21 men and 70 women, aged 27 to 66 years. A decrease in the cortisol level CONCLUSION: The obtained results confirm the need for screening for hypercortisolism in all patients with morbid obesity and type 2 diabetes scheduled for bariatric surgery.

Impaired intrarenal hemodynamics is one of the links in the pathogenesis of chronic kidney disease in type 2 diabetes (T2D); correction of these disorders is the target of drugs with nephroprotective activity, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors. The aim of our study was to evaluate the effect of the SGLT2 inhibitor empagliflozin on intrarenal blood flow parameters in patients with T2D. Material and methods . In an open prospective cohort singlecenter study, clinical and laboratory data were monitored before the start of treatment, on the 7th, 28th, 90th, and 180th day of taking empagliflozin 10 mg/day. The study of renal blood flow parameters was carried out using Doppler ultrasonography, peak systolic (PSV), end-diastolic, and mean velocity (MV) of blood flow, as well as resistance index (RI) of intrarenal arteries were assessed. Results and discussion . Forty patients with T2D and chronic kidney disease, chronic heart failure and/or atherosclerotic cardiovascular disease were included, 17 men and 23 women, aged 43 to 76 years. In the arteries of the cortex, on the 90th day of empagliflozin administration, a decrease in PVR and MV was observed compared to the period before the start of treatment (p < 0.001 and p = 0.004, respectively). This dynamics was maintained on the 180th day (p < 0.001). The lowest values of RI in the arteries of the renal cortex were observed on the 180th day (all p < 0.01 compared to the periods before treatment, on the 7th and 28th days of empagliflozin administration). IR of blood flow in the medulla decreased from the 7th to the 90th day (p = 0.003). The revealed changes in intrarenal hemodynamics were associated with the dynamics of serum creatinine and glycated hemoglobin A1c content, as well as of albuminuria. Conclusions . In patients with T2D, a decrease in intravascular resistance and blood flow rates in the kidney is observed on the 90–180th day of empagliflozin use. Changes in intrarenal blood flow are associated with the hemodynamic and metabolic response to empagliflozin.

BACKGROUND : Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been implemented into the treatment standards for chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). Identification of predictors of the protective effect of SGLT2 inhibitors on the kidneys remains an urgent task. AIM : To evaluate the effects of the SGLT2 inhibitor empagliflozin on the levels of biomarkers of renal injury, fibrosis and low-grade inflammation in patients with T2D with CKD and/or high cardiovascular risk. MATERIALS AND METHODS : This prospective cohort single-center study included 30 patients with T2D newly initiated treatment with an SGLT2 inhibitor. Before and on day 90 of treatment with empagliflozin (10 mg/day), urinary excretion of nephrin, retinol-binding protein 4 (RBP-4), type IV collagen, and fibrosis marker WFDC-2, as well as serum concentrations of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor receptor 1A alpha (TNFRSF1A) were determined by ELISA. Twenty healthy individuals were included in the control group. RESULTS : Patients with T2D compared to controls initially demonstrated higher excretion of nephrin (p=0.03), RBP-4 (p=0.001), type IV collagen (p=0.04) and WDFC-2 (p=0.02), as well as higher serum concentrations of hsCRP and TNFSF1A (p=0.03). Empagliflozin treatment was associated with a significant decrease in the excretion of RBP-4 (p=0.04) and TNFRSF1A levels (p0.05). Baseline RBP-4 excretion and serum TNFRSF1A levels were associated with changes in creatinine levels during empagliflozin treatment. CONCLUSION : In patients with T2D with CKD and/or high cardiovascular risk, empagliflozin treatment resulted in decreased urinary excretion of RBP-4 and serum TNFRSF1A levels. These data may indicate a protective effect of empagliflozin on tubular dysfunction and low-grade inflammation.

BACKGROUND : Deintensification of basal-bolus insulin therapy (BBIT) with simplification of the treatment regimen is a possible and necessary therapeutic strategy for some patients with type 2 diabetes (T2D). One of the options for deintensification is the transition to fixed combination of insulin glargine/lixisenatide (iGlarLixi). AIM : To determine the efficacy and safety of deintensification of BBIT in hospitalized patients with T2D by switching to iGlarLixi under continuous glucose monitoring (CGM). MATERIALS AND METHODS: Design: single-center, comparative, observational study in real-world settings. A total of 283 T2D patients on BBIT were included, 118 subjects underwent BBIT deintensification under CGM control according to clinical indications, 165 patients continued BBIT. Thirty patients were re-examined one year after deintensification. Time In target Range (TIR), Time Above Range (TAR), Time Below Range (TBR), as well as Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), Lability Index (LI), and Mean Absolute Glucose rate of change (MAG) were estimated. Endogenous insulin secretion was assessed by fasting and 2-hour postprandial C-peptide levels. The estimated glucose disposal rate (eGDR) was used as a measure of insulin sensitivity. RESULTS : The groups were similar in age, diabetes duration, glycated hemoglobin (HbA1c) and eGDR. Body mass index (BMI) and C-peptide levels were higher, while the duration of insulin therapy and initial daily insulin dose (DID) were lower in patients of the deintensification group (all pCONCLUSION : Switching to iGlarLixie is an effective therapeutic option for patients with T2D with normal C-peptide levels who require deintensification of BBIT.

BACKGROUND: The course of metabolic dysfunction-associated steatotic liver disease after bariatric surgery remains a critical clinical problem. AIM: To evaluate changes in noninvasive indices of hepatic steatosis and fibrosis in patients with morbid obesity and type 2 diabetes mellitus 1 year after bariatric surgery. METHODS: This study included 85 patients who underwent bariatric surgery at the Institute of Clinical and Experimental Lymphology between 2019 and 2024: mini-gastric bypass (n = 60) or sleeve gastrectomy with single-anastomosis ileal bypass (n = 25). Glycated hemoglobin (HbA₁c), triglyceride, low-density lipoprotein cholesterol, C-reactive protein, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and alkaline phosphatase levels were assessed before surgery and 1 year postoperatively. Moreover, noninvasive hepatic steatosis indices, namely, Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and St-index, were evaluated. Fibrosis indices included the Fibrosis Index Based on Four Factors (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Changes in parameters were analyzed using the Wilcoxon signed-rank test, whereas correlations were assessed with Spearman rank analysis. RESULTS: A 32% decrease in mean body weight was observed 1 year after surgery (p = 2.4 × 10⁻11), and 62 patients (72.9%) achieved clinical remission of diabetes. Significant decreases were observed in HbA1c (p = 1.4 × 10⁻11), triglycerides (p = 3.3 × 10⁻8), low-density lipoprotein cholesterol (p = 2.6 × 10⁻4), C-reactive protein (p = 2.1 × 10⁻8), alanine aminotransferase (p = 3.7 × 10⁻9), aspartate aminotransferase (p = 1.3 × 10⁻5), γ-glutamyltransferase (p = 9.0 × 10⁻6), and alkaline phosphatase (p = 7.6 × 10⁻5) and in all hepatic steatosis indices (FLI: p = 7.8 × 10⁻10; St-index: p = 5.3 × 10⁻11; HSI: p = 2.5 × 10⁻10; and LAP: p = 2.5 × 10⁻13). No significant changes were found in fibrosis indices (FIB-4: p = 0.208; NFS: p = 0.112). Decreases in steatosis indices were associated with weight loss (FLI: r = 0.503, p = 0.001; St-index: r = 0.425, p = 3.1 × 10⁻4; HSI: r = 0.853, p = 2.6 × 10⁻4; and LAP: r = 0.252, p = 0.008). Changes in LAP correlated with a decrease in HbA₁c (r = 0.355, p = 4.3 × 10⁻4), and changes in St-index and HSI were linked to changes in estimated glucose utilization rate (r = −0.502, p = 1.7 × 10⁻4 and r = −0.269, p = 0.001, respectively). CONCLUSION: In patients with morbid obesity and type 2 diabetes mellitus, noninvasive hepatic steatosis indices decreased and fibrosis indices remained unchanged 1 year after bariatric surgery (mini-gastric bypass or sleeve gastrectomy with single-anastomosis ileal bypass).

Insulin is used in the treatment of a significant proportion of patients with type 2 diabetes (T2D), while many patients do not achieve glycemic control targets. Aim of the study was to assess the achievability of target parameters of time in ranges and glucose variability (GV) in hospitalized patients with T2D during insulin therapy adjustment under the control of continuous glucose monitoring (CGM) and to determine factors influencing these parameters. Material and methods . A retrospective comparative single-center study was conducted in real world settings. Patients were divided into 3 groups: 1) basal insulin (BI) therapy; 2) pre-mixed insulin (PMI) therapy; 3) basal-bolus insulin therapy (BBIT) in the mode of multiple daily injections. Time in the target range (TIR), time in the range above and below the target (TAR L-1, TAR L-2, TBR-L1, TBR L-2), coefficient of variability (CV), mean amplitude of glucose excursions (MAGE), lability index (LI), and mean absolute glucose rate of change (MAG) were derived from CGM recordings. Results . The study recruited 371 patients (167 were on BI, 40 on PMI, and 164 on BBIT). The mean glucose level, TIR, TBR, and TAR L-1 did not differ between three groups. TAR L-2 values and GV indices (CV, MAGE, LI) were higher in patients on BBIT than in those on BI. Patients on PMI did not show significant differences from other groups. In multivariate regression analysis, C-peptide level turned out to be an independent predictor of CV, MAGE, and LI; body mass index was associated with MAG and LI. Conclusions. Correction of insulin therapy under the CGM control allows achieving target glucose values in most patients with T2D. Patients on BBIT have higher GV than those on BI at similar TIR. The GV parameters in patients with T2D on insulin therapy are inversely associated with endogenous insulin secretion (C-peptide level).

Obesity in patients with type 1 diabetes (T1D) is an increasingly important problem in diabetology. According to recent studies, the prevalence of overweight and obesity among patients with T1D varies from 15 to 50%. About a quarter of patients with T1D have metabolic syndrome. On the one hand, weight gain in patients with T1D reflects a general population trend. On the other hand, diabetes-related factors such as basal-bolus insulin therapy, chronic insulin overdose, hypoglycemia, and psychological problems associated with the disease can be promoters of weight gain. The relationship between T1D and obesity can be bidirectional. It has been established that overweight and obesity increase the risk of T1D, probably contributing to the autoimmune destruction of beta cells. Individuals with overweight and obesity, compared with patients with normal body weight, more often have insulin resistance, dyslipidemia and require higher doses of insulin to achieve targets of glycemic control. Obesity in individuals with T1D a risk factor for diabetic microvascular complications, arterial hypertension, chronic kidney disease, chronic heart failure, cardiovascular events, non-alcoholic fatty liver disease, and is associated with increased mortality. Therefore, maintaining normal body weight should be considered as an important option in the management of T1D. Education, moderate calorie restriction diet, and physical activity are the basis of the strategy for the prevention and treatment of obesity in individuals with T1D. Glucagon-like peptide-1 agonists, dual agonists of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, sodium-glucose cotransporter 2 inhibitors, and metformin are considered promising therapeutic options; however, data on the efficacy and safety of these drugs in patients with T1D are still limited. Experience in performing bariatric interventions in individuals with T1D and morbid obesity is accumulating. Further research is needed to create programs for the prevention and treatment of obesity in patients with T1D.

Continuous glucose monitoring (CGM) has been established as a method for self-assessment glucose levels in individuals with diabetes mellitus in the Russian Federation for more than 15 years. The main characteristics of CGM sensors are its’ accuracy and performance that ensure their effectiveness and safety. Currently, there are no standardized guidelines that outline the minimum accuracy standards for CGM systems.This review is aimed to codify the current methods for evaluating CGMs accuracy and performance across the different countries, as well as to propose local Russian guidelines on CGM device accuracy evaluation. This involves guidelines for the design of clinical trials to assess sensors accuracy and the minimum acceptable performance requirements for CGM devices to be utilized in clinical settings.