Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.

Liver Steatosis: Better Predictor of CKD in MAFLD Than Liver Fibrosis as Determined by Transient Elastography With Controlled Attenuation Parameter

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP).Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold.Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values >353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values >353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values.Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome.

Non-alcoholic fatty liver disease as an independent factor of cardiometabolic risk of cardiovascular diseases

Non-alcoholic fatty liver disease (NAFLD) is a pressing public health problem affecting up to a third of the world's adult population. The main reasons for its high mortality rate are cardiovascular diseases. They are caused by subclinical atherosclerosis characteristic of NAFLD, venous thromboembolic complications, functional and structural myocardial disorders, calcification of heart valves, heart rhythm and conduction disturbances. At the same time, NAFLD can serve as an independent factor of the cardiometabolic risk of their development, which is associated with atherogenic dyslipidemia, as well as the release of numerous pro-inflammatory mediators both from the pathologically altered liver and as a result of systemic endotoxemia, which is the result of disturbance of the intestinal microbiota, accompanied by a decrease in intestinal microbial gene richness., a change in its composition and function, followed by bacterial translocation. Considering that most patients with NAFLD die from cardiovascular complications, it becomes obvious that exclusively “liver-oriented” principles of their treatment cannot be sufficient, but require a multidisciplinary team approach involving cardiologists, cardiac surgeons and doctors of other related specialties.

Glycoprotein Profile Measured by a 1H-Nuclear Magnetic Resonance Based on Approach in Patients with Diabetes: A New Robust Method to Assess Inflammation

Patients with type 2 diabetes mellitus (T2DM) and atherogenic dyslipidemia (AD) are at higher risk of developing cardiovascular diseases (CVDs), so an interest in discovering inflammation biomarkers as indicators of processes related to CVD progression is increasing. This study aims (a) to characterize the plasma glycoprotein profile of a cohort of 504 participants, including patients with and without T2DM and/or AD and controls, and (b) to study the associations between the glycoprotein profile and other lipid and clinical variables in these populations. We characterized the plasma glycoprotein profiles by using 1H-NMR. We quantified the two peaks associated with the concentration of plasma glycoproteins (GlycA and GlycB) and their height/width ratios (H/W GlycA and H/W GlycB), as higher and narrower signals have been related to inflammation. We also quantified GlycF, the signal of which is proportional to the concentration of the acetyl groups of free N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic in the samples. The lipoprotein profile was also determined (Liposcale®). Standard clinical and anthropometric measurements were taken. Multivariate classification models were developed to study the differences between the study groups. Reduced HDL-C levels, increased small dense LDL and HDL particles, and elevated TG levels were significantly associated with glycoprotein variables. Glycoprotein values in the diagnostic groups were significantly different from those in the CT groups. AD and DM conditions together contribute to a positive and significant synergetic effect on the GlycA area (<0.05) and the H/W ratios of GlycA (<0.01) and GlycB (<0.05). By adding the new glycoprotein variables to the traditionally used marker of inflammation C-reactive protein (CRP), the AUC increased sharply for classification models between the CT group and the rest (0.68 to 0.84), patients with and without dyslipidemia (0.54 to 0.86), and between patients with and without diabetes (0.55 to 0.75). 1H-NMR-derived glycoproteins can be used as possible markers of the degree of inflammation associated with T2DM and AD.

Incidence of Erectile Dysfunction in Patients of Diabetes Mellitus

Aim: The goal of this study was to determine how frequent erectile dysfunction is in diabetic people and what factors contribute to this condition. Methods: In this study, type-2 diabetes patients were selected among outpatients who visited Diabetes Clinics regularly. For the first selection of patients, it was essential to have had a diagnosis of type 2 diabetes for at least six months but no more than 10 years. 1,080 male diabetic patients (with or without active ED symptoms) who visited the institute's Medicine or Psychiatry Outpatient Departments were included in the study throughout the period under consideration. The individuals' body mass index (BMI), blood sugar levels, and lipid profile were all measured. Erectile dysfunction became more common as people became older. ED was shown to be associated with elevated hemoglobin A1c (HbA1c), as well as hypertension, atherogenic dyslipidemia (low HDL-cholesterol and high triglycerides), metabolic syndrome, and depression in the study population. Male erectile dysfunction (ED) has been demonstrated to be prevented by physical activity, with men who exercised more being 10 percent less likely to develop ED than those who did not. Results: Erectile dysfunction was shown to be prevalent in 32.21 percent of men. Patients with erectile dysfunction had a substantially higher mean age (58.4010.96 years) than those who did not have erectile dysfunction (51.0011.16 years) (p0.001). Conclusion: In conclusion, glycemic control and other metabolic variables were linked to ED risk in people with type 2 diabetes, having a greater degree of physical activity was protective.

Plasma atherogenic indices are independent predictors of slow coronary flow

Background Although the pathophysiology of coronary slow flow (CSF) has not been fully elucidated, emerging data increasingly support potential role for subclinical diffuse atherosclerosis in the etiology of CSF. We aimed to investigate relationship between atherogenic indices and CSF. Methods 130 patients with CSF diagnosed according to Thrombolysis in Myocardial Infarction (TIMI)-frame count (TFC) method and 130 controls who had normal coronary flow (NCF) were included in this retrospective study. Atherogenic indices (atherogenic index of plasma [AIP], Castelli risk indices I and II [CRI-I and II]) were calculated using conventional lipid parameters. Results The logistic regression analyses demonstrated that AIP (OR, 5.463; 95% confidence interval [CI], 1.357–21.991; p = 0.017) and CRI-II (OR, 1.624; 95% CI, 1.138–2.319; p = 0.008) were independent predictors of CSF. Receiver operating characteristic analysis showed that the optimal cutoff value to predict the occurrence of CSF was 0.66 for AIP (sensitivity, 59%; specificity, 73%; area under curve [AUC], 0.695; p < 0.001) and 3.27 for CRI-II (sensitivity, 60%; specificity, 79%; AUC, 0.726; p < 0.001). Conclusions AIP and CRI-II levels were independent predictors of CSF. Prospective studies in larger cohorts of patients may elucidate the role of atherogenic dyslipidemia in the pathophysiology of CSF.

State of metabolic processes and ways to improve them in premenopausal women due to the life extension strategy

Increasing the duration and improving the quality of life of older women is a significant problem of current medicine. Metabolic disorders in the form of type II diabetes mellitus and atherogenic dyslipidemia lead to a significant level of cardiovascular complications. It is known that hormone replacement therapy cannot normalize age-related metabolic disorders. Therefore, the search for new methods of cardiovascular health is extremely relevant. Research objective: to study the state of autonomic nervous regulation, carbohydrate and lipid metabolism in perimenopausal women using the life extension approach.Materials and methods. Group I (control) consisted of 35 apparently healthy women of reproductive age. Group II (main) consisted of 71 patients whom was administered a solution of xylitol with electrolytes (Xylate) by infusion from the first days of the reduction diet for 5 days, and also L-arginine (Tivortin) was injected intravenously for 5 days, 200 ml once a day, followed by taking a drinking solution of this drug for another three weeks. All patients followed a 28-day diet, and also performed daily aerobic morning exercises for 3 months.Results. A significant decrease in body mass index in patients of the main group due to the proposed treatment and prevention program was found. At the same time, Kupperman index declined significantly. Decreased body mass index in patients of the main group was the basis for improved autonomic nervous regulation and metabolic processes. Xylate-Tivortin complex has allowed emphasizing the overcoming of insulin resistance, dyslipidemia and chronic inflammation.Conclusions. The developed 3-month program allowed to significantly improving the metabolic processes and hemodynamic parameters in women of perimenopausal age. This is the basis for the introduction of Xylate-Tivortin complex life extension into the practice of family physicians, obstetricians and gynecologists and specialists in the field of aesthetic medicine.

Epicardial adipose tissue volume and myocardial ischemia in asymptomatic people living with diabetes: a cross-sectional study

Background Epicardial adipose tissue (EAT) is considered a novel diagnostic marker for cardiometabolic disease. This study aimed to evaluate whether EAT volume was associated with stress-induced myocardial ischemia in asymptomatic people living with diabetes—independently of confounding factors—and whether it could predict this condition. Methods We included asymptomatic patients with diabetes and no coronary history, who had undergone both a stress a myocardial scintigraphy to diagnose myocardial ischemia, and a computed tomography to measure their coronary artery calcium (CAC) score. EAT volume was retrospectively measured from computed tomography imaging. Determinants of EAT volume and asymptomatic myocardial ischemia were evaluated. Results The study population comprised 274 individuals, including 153 men. Mean (± standard deviation) age was 62 ± 9 years, and 243, 23 and 8 had type 2, type 1, or another type of diabetes, respectively. Mean body mass index was 30 ± 6 kg/m2, and mean EAT volume 96 ± 36 cm3. Myocardial ischemia was detected in 32 patients (11.7%). EAT volume was positively correlated with age, body mass index and triglyceridemia, but negatively correlated with HbA1c, HDL- and LDL-cholesterol levels. Furthermore, EAT volume was lower in people with retinopathy, but higher in men, in current smokers, in patients with nephropathy, those with a CAC score > 100 Agatston units, and finally in individuals with myocardial ischemia (110 ± 37 cm3 vs 94 ± 37 cm3 in those without myocardial ischemia, p < 0.05). The association between EAT volume and myocardial ischemia remained significant after adjustment for gender, diabetes duration, peripheral macrovascular disease and CAC score. We also found that area under the ROC curve analysis showed that EAT volume (AROC: 0.771 [95% confidence interval 0.683–0.858]) did not provide improved discrimination of myocardial ischemia over the following classic factors: gender, diabetes duration, peripheral macrovascular disease, retinopathy, nephropathy, smoking, atherogenic dyslipidemia, and CAC score (AROC 0.773 [0.683–0.862]). Conclusions EAT may play a role in coronary atherosclerosis and coronary circulation in patients with diabetes. However, considering EAT volume is not a better marker for discriminating the risk of asymptomatic myocardial ischemia than classic clinical data.

Analysis of the impact on the health care budget and consumers of the use of the preparation of omega-3 acid ethyl esters90 in the treatment of patients with atherogenic dyslipidemia

Aim To evaluate economic results of using omega-3 acid ethyl esters 90 for primary prevention of cardiovascular catastrophes in patients with residual hypertriglyceridemia (HTG).Material and methods The economic evaluation of using the medicine omega-3 acid ethyl esters 90 in the system of drug provision of the population of the Russian Federation was performed by analyzing the effect on the budget using a pharmacoeconomic model developed with the Microsoft Office Excel 2016 software. The effect of omega-3 acid ethyl esters 90 was evaluated in 555 643 patients with residual HGT (Moscow). The study lasted for one year. Results of the meta-analysis by A.A. Bernasconi et al. (2020) were used as a source of efficacy data. The following direct and indirect medical expenses for treatment of cardiovascular complications of residual HTG were taken into account in this study: expenses for drug therapy; expenses for therapy and rehabilitation for nonfatal complications; expenses for fatal outcomes; state support for disability; foregone per capita gross domestic product resulting from losses of earnings due to temporary incapacity to labor by people of work-able age; and salary payments for temporary incapacity to work.Results Using omega-3 acid ethyl esters 90 in 555 643 patients with residual HTG will allow preventing 1 437 fatal ischemic cardiovascular complications (including 564 deaths from ischemic heart disease and 1 128 cases of myocardial infarction (MI), including 558 fatal cases of MI). Furthermore, the difference in expenses compared to the high-dose statin treatment alone will be 359 252 253 rubles or 0.32 %.Conclusion The results of this comprehensive pharmacoeconomical study showed that the use of omega-3 acid ethyl esters 90 in patients with residual HGT is an economically preferrable strategy compared to high-dose statin treatment alone and does not influence significantly the budgetary expenses as a part of the State Guarantee of Free Medical Care to the Citizens of the Russian Federation (increase in expenses by 0.32 % compared to the current practice). At the same time, the use of omega-3 acid ethyl esters 90 results in a 10% decrease in the number of fatal ischemic cardiovascular complications.