Metabolic Syndrome Insulin Resistance Research Articles

Chaihu Shugan powder restores fatty acid synthesis to alleviate insulin resistance in metabolic syndrome by regulating the LXRα/SREBP-1 signaling pathway.

Metabolic syndrome (MS) is a significant risk factor for cardiovascular and cerebrovascular diseases, primarily driven by insulin resistance (IR). Although the herbal compound Chaihu Shugan powder (CSP) has demonstrated the potential to improve IR in animal models of MS, its mechanism of action remains incompletely understood. Therefore, this study aimed to investigate the biological pathways through which CSP exerts its therapeutic effects on IR in MS using both in vitro and in vivo methods. The primary metabolites of CSP aqueous extract and CSP-containing serum were measured by LC-MS/MS. A mouse model of MS-related IR was induced by a high-fat, high-fructose diet combined with chronic immobilization stress. The CSP's therapeutic potential was evaluated through glucose and insulin tolerance tests and hepatic insulin signaling molecules (p-IRS-1, IRS-1, p-Akt, and Akt). The expression of lipid metabolism-related factors (FFA, DAG, LXRα, SREBP-1, FASN, and ACC) in the liver was also measured. Hepatocyte IR was modeled using high-glucose and high-insulin conditions, and CSP impact was evaluated using 2-NBDG uptake and insulin signaling molecule expression. The specific mechanism of CSP was explored using the LXRα agonist T0901317. The MS-related IR model exhibited a decreased p-Akt/Akt ratio and increased fasting glucose, insulin, homeostatic model assessment of IR, and hepatic lipid metabolism factors. Treatment with CSP mitigated these effects. In the hepatocyte IR model, CSP-containing serum improved glucose uptake and modulated the expression of insulin signaling and lipid metabolism factors. Furthermore, T0901317 reversed the beneficial effects of CSP, indicating the role of LXRα in CSP's therapeutic action. The CSP ameliorated IR in MS by restoring fatty acid metabolism through the regulation of the LXRα/SREBP-1 signaling pathway.

Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome.

In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers. In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging. Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, p = 1.79 × 10-9) and visceral adipose tissue (rho = 0.35, p = 6.80 × 10-9). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn. MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.

Analysis of Serum Chemerin Level in Acanthosis Nigricans Patients: A Case Control Study

Abstract Background Acanthosis nigricans (AN) describes clinically a darkly pigmented thickening skin, which demonstrates epidermal/dermal hyperplasia with orthokeratotic hyperkeratosis and papillomatosis of stratum spinosum with basal layer hyperpigmentation, in the absence of actual acanthosis and melanocytosis in histology. Aim of the Work The aim of our work was assessment of serum concentrations of Chemerin level in obese patients with AN and the healthy control group, as well as evaluation of a possible correlation between chemerin concentrations and metabolic syndrome components. Patients and Methods Our study included 75 subjects, divided into three groups. The first group included 25 obese patients with AN, the second group included 25 obese patients without AN. In addition to the control group which included 25 healthy individuals. Each subject was assessed for blood pressure, body mass index and waist hip ratio. 3ml blood sample was taken from each subject. Lipid profile, serum glucose level, fasting serum insulin were measured. Chemerin concentration was assessed by quantitative ELISA. Results In our study, 100% of the included obese patients with AN and 88% of those without AN had metabolic syndrome. No statistically significant difference between them as regards BMI, SBP, DBP, WHR, fasting Insulin (P > 0.05). However, statistically significant higher levels of serum, Cholesterol, TG, HDL, and LDL were observed in obese patients with AN compared with those without AN (P ≤ 0.001). This result showed that AN is a clinical surrogate for laboratory-determined hyperinsulinemia and insulin resistance indicating the highest risk for type 2 diabetes. Conclusion Acanthosis Nigricans has been demonstrated to be a useful screening marker for obesity and insulin resistance. In addition, there is correlation between chemerin concentrations and acanthosis nigricans. Serum chemerin could be considered one of the metabolic risk factors leading to insulin resistance in metabolic syndrome and may represent a novel marker of these derangement.

CORRECTION OF CHANGES IN LIPID METABOLISM AND REDOX SYSTEM IN PATIENTS WITH STEMI IN THE SETTING OF INSULIN RESISTANCE

Myocardial infarction (STEMI) remains one of the most important problems of modern Cardiology both in Ukraine and worldwide due to its recalcitrant indices of incidence, disability and mortality. The prevalence of metabolic syndrome (MS) and DM2 in Ukraine is quite high, accounting for 20-28% in the general population and over 50% in certain demographics. In persons with abdominal obesity, metabolic syndrome and DM2, there is a 30% total risk of developing MI in the next 8 years, and their mortality rate is double thatof persons without metabolic disorders. The unfavorable prognosis in such patients is attributed to insulin resistance as an additional risk factor for CAD progression and the development of ACS, which determines the need to develop methods for correction of these abnormal processes.
 The aim of the research: to explore the efficacy of correcting the disorders of lipid profile and prooxidant/antioxidant system balance in patients with STEMI in a setting of insulin resistance and high risk of reperfusion complications by using dapagliflozin, a SGLT2 inhibitor.
 The methods of the research. The basis of the work has been underlain by the analysis of a comprehensive assessment and surgical treatment (percutaneous coronary intervention) in 73 patients with STEMI in the setting of insulin resistance in MS and DM2. The parameters of lipid profile and the activity of the components in the prooxidant/antioxidant system were determined by spectrophotometric methods; the absorbancy was measured on a Biomat 5 spectrophotometer (United Kingdom).The diagnosis of ACS was verified according to ESC Guidelines in the presence of a typical anginal attack, ACS-specific ECG changes with time (reciprocal ST displacement) and the signs of necrosis-resorption syndrome.The diagnosis was subsequently confirmed by the results of urgent coronary angiography. The diagnosis of MS and type 2 DM was made according to the recommendations of the WHO Expert Committee (2013) and the updated ADA/EASD consensus (2018).
 Results. In order to improve lipid profile and redox system balance in pre- and postoperative period, the patients were prescribed dapagliflozin at the dose of 10 mg/day, which allowed compensation of hyperglycemia, reduction of insulin resistance and stabilizing the activity of prooxidant/antioxidant system, preventing post-PCI reperfusion complications and stabilizing the clinical condition of comorbid patients in the postoperative period owing to a 40.4% reduction in the incidence of rhythm and conductivity disorders, and a 55.3% reduction in manifestations of acute heart failure. There has been a substantial reduction in free radical oxidation in the setting of dapagliflozin treatment, as suggested by a 1.3-fold reduction (р<0.05) in active products of thiobarbituric acid in the serum and a simultaneous restoration of functioning of enzymatic antioxidant systems, a 1.5-fold reduction (p<0.05) in the degree of superoxide dismutase blockage with an increased activity of catalase and ceruloplasmin.
 Conclusions. The use of dapagliflozin in pre- and postoperative patients with STEMI in the setting of insulin resistance and high surgical risk contributes to improvement of lipid metabolism and a significant reduction in the activity of free radical oxidation with restoration of functioning of enzymatic antioxidant systems in the body, which allows for a significant reduction in the incidence of rhythm and conduction disorders and the manifestations of acute heart failure.

Evaluation of specific IgG content to nutritional antigens in patients with metabolic syndrome

Specific antibodies to food antigens are detected both in healthy individuals and in various pathologies, including those of the gastrointestinal tract, neuro- and autoimmune diseases. In fact, there are no studies concerning the level of specific IgG to food antigens in metabolic syndrome. A comparative analysis of the concentration of specific IgG to food antigens in patients with metabolic syndrome and healthy people was carried out. The goal was to determine the concentrations of specific IgG to food antigens in patients with metabolic syndrome. Material and methods. A survey of 100 patients with metabolic syndrome and 100 practically healthy people was carried out. The content of low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides and glucose, specific IgG antibodies to food allergens, insulin, interleukin-6 and tumor necrosis factor α was determined in the blood serum. Results. A comparative analysis of the level of specific IgG to food antigens in patients with metabolic syndrome and practically healthy people was carried out. The spectrum of the most frequently detected IgG to food antigens in metabolic syndrome was similar to that in practically healthy people, but their average level was higher and elevated levels were more often recorded. It has been shown that the range of specific IgG detected was interconnected with impaired glucose utilization. Higher concentrations of IgG to meat and fish products were recorded in patients with insulin resistance, in the absence of insulin resistance higher levels of IgG to dairy products were revealed. Conclusion. In the metabolic syndrome, an increase in the permeability of the intestinal barrier and a state of chronic mild inflammation are associated with a more active intake of food antigens, leading to an activation of the immune system, with an increase in the production of specific IgG. This can significantly increase the risk of developing pathological neuro- and autoimmune diseases in patients with metabolic disorders. Insulin resistance in metabolic syndrome is associated with higher concentrations of IgG to meat and fish products, ie. food antigenic specificity may play a regulatory influence in the formation of impaired glucose utilization.

“SERUM URIC ACID LEVELS WITH INSULIN RESISTANCE IN METABOLIC SYNDROME – A CORRELATION STUDY”

Background: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, which is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The increasing prevalence of Obesity across the world will result in an increased prevalence of Metabolic syndrome. However, obesity along with the MetS increases the risk of acquiring Diabetes and cardiovascular diseases (CVD). The prevalence of metabolic syndrome in adults ranges from 20 to 25%, but in those with type 2 diabetes, it can almost always approach 80%. The death rate from high BMI has increased globally by 28.3%. According to the WHO denition of metabolic syndrome, CVD mortality was 2.6 to 3.0 times higher and all-cause death was 1.9 to 2.1 times higher. Elevated uric acid is one of the characteristic signs of metabolic syndrome patients that has been associated with several cardiometabolic risk factors. Despite frequently being thought of as secondary to hyperinsulinemia, current research suggests that uric acid has a primary role in mediating this condition. According to multiple logistic regression analysis, the risk of MetS rose around 2-fold for every 1 mg/dl increase in blood uric acid. This study seeks to determine if insulin resistance and asymptomatic hyperuricemia are related in patients with metabolic syndrome. Aim: To study the correlation of Serum Uric acid levels with Insulin Resistance in Metabolic syndrome. Materials And Methods: A Hospital-based cross-sectional study was conducted in the Department of General Medicine, Santhiram medical college, and the general hospital for six months. A total of 50 cases with asymptomatic Hyperuricemia and insulin resistance who satisfy the criteria for metabolic syndrome and patients that were admitted to the hospital during this period were taken into the study. Results: Out of 50 patients a male preponderance of 72% was found in the study. Subjects in the Metabolic syndrome group had higher BMI, WC, SBP, DBP, FBS, fasting insulin, HOMA-IR index, TG, and HDL levels than the subjects in the non-MetS group. In this study, the mean serum uric acid was signicantly higher in the MetS group than that in the non-MetS group. In the Mets group, the mean value of serum uric acid was 8.1±1.8mg/dl. In the study, 78.6% of women and 75.4% of men had asymptomatic hyperuricemia. In Mets, there was a strong positive correlation between serum uric acid and insulin resistance. Additionally, a favorable association between serum uric acid and several Mets factors such as BMI, waist size, fasting blood sugars, fasting insulin, and HDL was observed. Conclusion: Serum uric acid showed a signicant positive relation with insulin resistance in Mets. There was also a positive correlation noted between serum uric acid and various components of Mets i.e., BMI, waist circumference, fasting blood sugars, fasting insulin, and HDL

The Relationship between Serum Ferritin Level and Insulin Resistance in Metabolic Syndrome

Introduction: Insulin resistance and metabolic syndrome (MetS) are risk factors for diabetes mellitus, and their prevalence is increasing. Ferritin has emerged as a biomarker of low-grade inflammation in addition to its role in iron metabolism. The study aims to determine the correlation between ferritin and insulin resistance (IR) in MetS. Materials and Methods: In this study, ferritin, glucose (fasting), and HOMA-IR were measured from serum samples obtained from 98 MetS patients and 100 healthy volunteers. Serum ferritin, glucose, insulin, and HOMA-IR results were compared between the MetS and the control group. Correlation analysis was performed between ferritin and HOMA-IR in control and MetS patients. Results: Serum ferritin (Control: 93,9±30,13; MetS:200±57,31 ng/ml), glucose (Control: 100,9±11,86, 123,9±21,52 ng/dl), insulin (Control: 4,11±2,57; MetS:15,99±5,71 µU/ml) and HOMA-IR (Control: 1,04±0,74; MetS:5,07±2,33) revealed to be higher in MetS compared to control. The correlation between serum ferritin level and HOMA-IR in MetS patients was revealed. This correlation was not found in the control group. Conclusion: In MetS, high serum ferritin level increases insulin resistance. While the positive correlation of ferritin with insulin resistance occurs at high ferritin levels, this is not observed at low ferritin levels.

Evaluation of the Role of Vaspin and Insulin Resistance in Metabolic Syndrome

Background: At least three of the following five medical factors must be present in order for someone to be diagnosed with metabolic syndrome. These conditions include abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). There is a correlation between having metabolic syndrome and having an increased risk of getting cardiovascular disease and type 2 diabetes. The percentage of older people who are members of racial and ethnic minority groups is growing at an alarming rate. Insulin resistance, metabolic syndrome, and prediabetes are conditions that are intricately connected to one another and share characteristics in common. It is believed that the condition is caused by an underlying disease of energy use and storage called MetS, which is closely related to the already existing weight gain, also known as obesity, and sloth. The blood levels of vaspin, insulin, and the HOMA IR value all increase as a result of this, and the levels of a number of other parameters also change as a result. Patients and methods: A case control study was conducted in the form of a comparison between individuals who went to the consulting clinic for internal diseases during the study period, which lasted from December 2021 to February 2022. There were a total of 60 confirmed cases with metabolic syndrome and 30 healthy people, and their ages ranged from 24 to 67. Patients from the Salah El-Din Governorate and the surrounding areas had their insulin and vaspin levels tested using the Elisa instrument. Patients with metabolic syndrome were classified as having the condition based on their fasting blood glucose levels, triglyceride levels, HDL-C levels, systolic blood pressure, and waist circumference. This information was obtained from an organization affiliated with the International Diabetes Federation. The results: The following findings emerged from the research conducted, and it was discovered that the level of vaspin and the HOMA IR value were significantly higher in individuals diagnosed with metabolic syndrome as compared to healthy people. And a negative correlation with HDL-C, a positive correlation between vaspin, HOMA IR, and insulin levels, as well as a positive correlation with the level of fasting glucose; moreover, HOMA IR value was significantly higher in patients with the metabolic syndrome than in the controls without the metabolic syndrome. Keywords: metabolic syndrome, insulin resistance, and vaspin

Evaluation of Fetuin-A and Insulin Resistance among Iraqi Type 2 Diabetic Patients with and without Ischemic Heart Disease

Background: Diabetes mellitus (DM) is a metabolic disorder in which hyperglycemia is a characteristic feature due to impairment in insulin secretion, defective insulin action, or both reasons. One long-term complication is the ischemic heart disease (IHD) which is a major cause of morbidity and mortality. Insulin and fetuin-A are hormones that play a role in glucose metabolism regulation. Insulin is responsible for regulating glucose passage to the cells, while fetuin-A blocks insulin binding to its receptor, which is linked to insulin resistance in metabolic syndrome. Higher fetuin-A level patients have 4 times greater risk of developing IHD compared to patients with lower fetuin-A levels. Studies found that both hormones participate in the development of T2DM and IHD, beside their role in the pathophysiology of metabolic syndrome. Aim of the study: Evaluate serum fetuin-A concentrations in type2 diabetic (T2D) patients with and without IHD and compare them with healthy individuals. Assess serum glucose, insulin levels, and HOMA-IR in T2D patients and IHD and compare them with healthy individuals. Subjects and Methods: A case control study, that included 120 patients (60 have T2DM with IHD and 60 having T2DM without IHD age ranged from 30 to 70 years patient, who attended Al-Yarmouk Teaching Hospital and Iraqi Center for Myocardial Infarction, Medical City Hospital, Baghdad during the period from November 2020 until February 2021 and compare result with 60 healthy control which age ranged from 30 to 70 years. Female: male ratio is almost 1:1 in the three studied groups. The diagnosis of MI is based on medical reports, laboratory, and clinical tests for heart disease. Patients with neuropathy, retinopathy, thyroid dysfunction and liver diseases were excluded from the study. BMI, FBS, serum insulin, HOMA-IR, and fetuin-A were measured or calculated for each participant. Result: a statistical difference in BMI between participants is found; 46.70% of T2DM in the IHD group are obese. No significant association between disease duration and development of IHD is found. All the included markers showed statistical differences in mean ± SD between the diabetic and control group; fetuin-a mean ± SD level was 27.63 13.31, 12.39 ± 5.61 and 9.93 ± 5.1 in T2DM with IHD, T2DM without IHD and control group, respectively. There was no statistical association between the markers and fetuin-A except a moderate positive correlation with insulin. Conclusion: Fetuin-A can be used as a predictor of IHD development in diabetic patients.

Prevalence of Metabolic Syndrome and Insulin Resistance in a Sample of Adult ADHD Outpatients.

BackgroundHigh prevalence of Metabolic Syndrome (MS) was found in patients with schizophrenia and bipolar disorders. Insulin Resistance (IR) seems to mediate MS role in developing cardiometabolic consequences.AimsTo investigate the prevalence of MS, and the role of MS components and IR surrogate indexes in determining MS in adult ADHD outpatients.MethodsIn the present cross-sectional study, MS, defined according to the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATP III), and IR surrogate indexes were assessed on a consecutive sample of adult ADHD outpatients. Logistic regression analysis was performed to evaluate the effect of each ATP III component and IR surrogate index in determining MS.ResultsSeventeen out of 158 patients (10.8%, 95%CI = 0.064/0.167) fulfilled the ATP-III criteria for MS. A comprehensive comparison with prevalence in the reference population was hindered by the lack of patients over 60 in the study sample, however under this age no significant differences were found. Among MS components, blood triglycerides level (OR = 1.02, 95%CI=1.01/1.03, p = 0.001) was the main predictor for MS, followed by diastolic blood pressure (OR = 1.08, 95%CI=1.01/1.16, p = 0.024) and waist circumference (OR = 1.06, 95%CI=1.01/1.13, p = 0.029). Lipid Accumulation Product (LAP, OR = 1.0006, 95%CI=1.0003/1.0009, p < 0.001) outperformed Triglyceride-Waist Circumference (TG-WC, OR=1.03, 95%CI=1.01/1.04, p < 0.001) in predicting MS.ConclusionsMore attention should be paid not only to MS but also to each ATP III component of MS and LAP in ADHD patients both at first assessment and during follow-up process.

Correlation of insulin resistance with neutrophil to lymphocyte ratio and serum ferritin in male patients of metabolic syndrome.

To determine the correlation of insulin resistance with neutrophil-to-lymphocyte ratio and serum ferritin, and to evaluate whether NLR and serum ferritin can predict insulin resistance in metabolic syndrome. The cross-sectional analytical study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to 2019, and comprised male patients of metabolic syndrome and healthy controls. The correlation involving insulin resistance, serum ferritin and neutrophil-to-lymphocyte ratio was determined. Data was analysed using SPSS 22. Of the 210 subjects, 160(76.2%) were cases with a median age of 45 years (interquartile range: 39-50 years), and 50(23.8%) were controls with a median age of 41 years (interquartile range: 35-50 years). Serum ferritin, alanine aminotransferase, total neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio were significantly higher among the cases than the controls (p<0.05). Significant positive correlation of insulin resistance was observed with serum ferritin and neutrophil-to-lymphocyte ratio (p<0.05)) among the cases. Neutrophil-to-lymphocyte ratio significantly predicted insulin resistance among the cases (p<0.05). Neutrophil-to-lymphocyte ratio was fund to be a significant predictor of insulin resistance in metabolic syndrome.

Insulin Resistance Related to Metabolic Syndrome

Insulin resistance and metabolic syndrome are one of the major factors associated with higher risks of developing cardiovascular diseases and Type II Diabetes (T2D). Insulin resistance is believed to be one of the underlying causes of the development of T2D. There are numerous environmental and genetic factors influencing the development of these conditions, and while there have been many studies conducted on the topic, there are still many gaps in the scholarly literature on the topic. The interplay between genetic and environmental factors is quite complex, considering that there are many genes involved in the regulation of energy consumption as well as in the protective functions of an organism. Currently, the prevalence of insulin resistance among different populations ranges from 20% to 40%. Still, while the studies conducted before 2016 have found 88 loci associated with the development of T2D most of them are associated with secretion of insulin and function of -cell, and far fewer studies have identified loci associated with insulin resistance. This means that the vast majority of studies are either focused on the insulin response pathway or on the immune response to inflammatory processes caused by metabolic disorders. It can be concluded that biological and genetic mechanisms underlying the development of insulin resistance in metabolic syndrome are complex. For now, it is known that insulin resistance in metabolic syndrome develops due to malfunctioning insulin response pathway, or malfunctioning chronic inflammation response system, and other problems associated with energy and fatty acid metabolism. Considering that the rates of obesity and T2D indeveloping countries are alarming, it is highly important to develop effective evidence-based interventions targeting this problem. Key words; Insulin resistance, genetic factors, Metabolic Syndrome, environmental factors, fatty acid metabolism.

Metformin improves skeletal muscle microvascular insulin resistance in metabolic syndrome.

Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance have not been defined. Eleven subjects with nondiabetic metabolic syndrome were studied four times (before and after 12 wk of treatment with placebo or metformin) using a crossover design, with an 8-wk washout interval between treatments. On each occasion, we measured three indices of large artery function [pulse wave velocity (PWV), radial pulse wave separation analysis (PWSA), brachial artery endothelial function (flow-mediated dilation-FMD)] as well as muscle microvascular perfusion [contrast-enhanced ultrasound (CEU)] before and at 120 min into a 150 min, 1 mU/min/kg euglycemic insulin clamp. Metformin decreased body mass index (BMI), fat weight, and % body fat (P < 0.05, each), however, placebo had no effect. Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P < 0.01), PWV, and FMD after insulin were unaffected by metformin treatment. PWSA improved with insulin only after metformin P < 0.01). Insulin decreased muscle microvascular blood volume measured by contrast ultrasound both before and after placebo and before metformin (P < 0.02 for each) but not after metformin. Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin. Metformin's effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects. Metformin did not improve aortic stiffness or brachial artery endothelial function, but enhanced radial pulse wave properties consistent with relaxation of smaller arterioles.NEW & NOTEWORTHY Metformin, a first-line treatment for type 2 diabetes, is often used in patients with insulin resistance and metabolic syndrome. Here, we provide the first evidence for metformin improving muscle microvascular insulin sensitivity in insulin-resistant humans. Simultaneously, metformin improved muscle glucose disposal, supporting a close relationship between insulin's microvascular and its metabolic actions in muscle. Whether enhanced microvascular insulin sensitivity contributes to metformin's ability to decrease microvascular complications in diabetes remains to be resolved.

Insulin resistance in metabolic syndrome depending on the occurrence of its components.

Metabolic syndrome (MetS) is described as a cluster of several commonly occurring disorders including abdominal obesity, hypertension (HT) (≥ 130/85 mm Hg), carbohydrate disorders: impaired fasting glucose or type 2 diabetes mellitus and lipids disorders such as hypertriglyceridaemia (TG), and low levels of high-density-lipoprotein cholesterol (HDL-C). Insulin resistance (IR) is defined as a glucose homoeostasis disorder involving a decreased sensitivity of muscles, adipose tissue, liver, and other body tissues to insulin, despite its normal or increased concentration in blood. The study group included 424 subjects with MetS (260 females, 164 males). All patients were recruited for 24 months from the Internal Ward of the District Hospital in Wąbrzeźno, Poland and the Department of Endocrinology and Diabetology Collegium Medicum in Bydgoszcz, Poland. The diagnosis of the MetS was made on the basis of International Diabetes Federation (IDF) criteria. MetS diagnosis was established when three or more criteria were met. To evaluate and measure IR, a hyperinsulinaemic-euglycaemic clamp was performed in each patient. IR was also determined through HOMA-IR. All patients of the study group were diagnosed with obesity, 73.5% with high fasting glucose levels, 66.9% with HT, 48.3% with lower level of HDL-C, and 38.2% with TG. It did not have an influence on the IR results. The study group was divided into 6 subgroups according to the constellation of 3 particular components of MetS (O + DM2T + ↑TG; O + HT + DM2T; O + DM2T + ↓HDL-C; O + HT + IFG; O + HT + ↑TG and O + HT + ↓HDL-C). IR of different degree was diagnosed in all patients of the study group. The results of our study showed that the highest IR was observed in patients with central obesity accompanied by DM2T and ↑TG. Also in subgroups with DM2T and HT or DM2T and ↓HDL-C, a high index of IR was noticed. The occurrence of IR in patients with MetS is obvious. However, despite the fact that they are high or very high cardiovascular risk patients, they are not a homogeneous group. Such patients differ from each other depending on the presence and constellation of particular disorders that make up the diagnosis of the MetS. Patients with MetS are a heterogeneous group differing in degree of IR and the risk of CVD.

Role of Vitamin D in Prevention of Metabolic Syndrome and Cardiovascular Diseases

Objective: About 90% of cardiovascular diseases can be prevented. In recent years, the role of vitamin D in the prevention of cardiovascular disease and components of metabolic syndrome has been actively discussed. The study aimed to investigate the possible influence of vitamin D3 on the emergence risk of metabolic syndrome and adverse cardiovascular events.&#x0D; Materials and methods: The study enrolled a total of 336 people (170 males and 166 females) aged 50-60 years. For comparative analysis, two groups were formed: Group 1 group involved 150 people treated with placebo, and Group 2 group included 186 people who received vitamin D3 orally in a dose of 2000 IU/day. The duration of treatment and observation was four years. Participants in the study completed a questionnaire developed by the authors of this paper, in which they answered questions about the presence of factors contributing to the development of cardiovascular pathology.&#x0D; Results and Discussion: Daily oral intake of vitamin D3 in a dose of 2000 IU/day for four years did not improve laboratory indicators, which are components of MS, namely, the content in the blood of TC, TG, LDL, HDL, AI, fasting and postprandial glycemia, insulin, and insulin resistance index HOMA2-IR (p&gt;0.05). Prolonged use of vitamin D3 did not reduce the risk of cardiovascular diseases (myocardial infarcts (RR=0.93, 95% CI [0.21-4.09], p=0.92), strokes (RR=1.24, 95% CI [0.18-8.70], p=0.83), stenting (RR=1,23, 95% CI [0.32-4.88], p=0.76), arterial hypertension (RR=1.12, 95% CI [0.47-2.68], p=0.81), as well as cardiovascular death rates (RR=0.83, 95% CI [0.14-4.88], p=0.83) and death from any other causes (RR=0.93, 95% CI [0.21- 4.09], p=0.92).&#x0D; Conclusion: Thus, daily prolonged oral administration of vitamin D3 in a dose of 2000 IU/day does not contribute to the improvement of blood lipid spectrum, glycemia, and insulin resistance in metabolic syndrome and does not reduce the risk of adverse (fatal and non-fatal) cardiovascular events.&#x0D; Bangladesh Journal of Medical Science Vol.20(2) 2021 p.431-438

Microbiota-derived extracellular vesicles and metabolic syndrome.

Metabolic syndrome is a major health problem concerning approximately 25% of worldwide population. Metabolic syndrome regroups a cluster of five metabolic abnormalities predisposing to Type 2 Diabetes mellitus. Dysbiotic gut microbiota is accompanied by an increase of both intestinal permeability and pathogen-associated molecular patterns translocation into blood circulation to induce metabolic endotoxemia responsible for the low-grade systemic inflammation and insulin resistance in metabolic syndrome. Among pathogen-associated molecular patterns, bacterial extracellular vesicles are gaining growing attention. The latter are produced by eukaryotic and prokaryotic cells and are vectors of communication between gut microbiota and its host The present review brings evidence to the importance of the control of the balance between the different subsets of gut microbiota in the development of metabolic diseases including metabolic syndrome. The ability of bacteria, including gut bacteria, to release extracellular vesicles implicated in host metabolic homeostasis is highlighted with their plethora of actions on intestinal barrier, inflammation and insulin resistance. Bacterial extracellular vesicles can be considered as key players in the pathophysiological of metabolic diseases and may represent an interesting strategy for specific manipulations of microbiome for promoting host health.

Estimation of prostate specific antigen in metabolic syndrome- a study in south Indian male population

Introduction: The main aim of our study was to assess the role of prostate specific antigen in Indian males and to determine its correlation with insulin resistance in metabolic syndrome. Materials and Methods: For this study, 62 male subjects of 40-65 years having metabolic syndrome were selected. Body mass index, fasting blood sugar, serum prostate specific antigen, serum fasting insulin and insulin resistance were analyzed using multivariate regression analysis and Annova test. Results and Conclusion: There was no statistically significant difference between body mass index and prostate specific antigen, body mass index and insulin resistance, prostate specific antigen and triglyceride, prostate specific antigen and high density lipoprotein, and prostate specific antigen and fasting blood sugar. Keywords: Body mass index, Insulin resistance and Obesity, Prostate specific antigen.

Dyrk1b Displaces Fkbp12 from mTORC2, Causes its Activation and Triggers De Novo Lipogenesis: Implications for the Treatment of Diet-Induced Fatty Liver Disease

The mechanisms that unify the association of insulin-induced de novo lipogenesis (DNL) with hepatic insulin resistance in metabolic syndrome (MetS) are not understood. We had previously shown that rare mutations in the DYRK1B gene are associated with MetS. We now demonstrate that Dyrk1b is a missing link between DNL and hepatic insulin resistance. The increased levels of liver Dyrk1b promoted, while its disruption conferred protection against enhanced glucose production, liver insulin-resistance and steatosis in mice. Mechanistically, Dyrk1b facilitated insulin-induced DNL in a kinase-independent manner by displacing Fkbp12 from mTORC2, causing its activation. Accordingly, the disruption of the hepatic mTORC2 rescued Dyrk1b induced hepatic steatosis and hyperlipidemia. The significance of this disease pathway is further illustrated by increased hepatic Dyrk1b levels in mice and humans with hepatic steatosis. These findings identify Dyrk1b and Fkbp12 as regulators of DNL in the setting of hepatic insulin resistance and attractive therapeutic targets against metabolic syndrome.

High-intensity Interval Training Low-volume Vs Moderate-intensity Continuous Aerobic Training On Insulin Resistance In Metabolic Syndrome

Moderate-intensity continuous aerobic training (MICAT) and high-intensity interval training (HIIT) interventions improve insulin resistance (IR) and glycemic control in patients with metabolic syndrome (MS). Moreover, skeletal muscle mass negatively correlates with IR. However, there are contradictory results about the superiority of any of these interventions on the control of the glucose metabolism in MS. PURPOSE: to compare the efficacy of a HIIT-low volume protocol vs MICAT on the Homeostatic assessment model, glycated hemoglobin (HbA1c) and skeletal muscle mass, in adults with MS. METHODS: controlled, randomized, clinical trial using the minimization method, with two parallel groups for the purpose of showing superiority. Sixty patients with MS, of both genders, 40-60 years old, were included. A clinical evaluation, biochemical tests, an ergospirometry and a dual-energy X ray absorptiometry to determine total and regional skeletal muscle mass were carried out before and after a treadmill exercise program of 12 weeks, 3 sessions/week. Participants were assigned to an intervention with HIIT-low volume (n=29) in 22 min sessions that included six intervals at a load of 90% of maximum oxygen consumption (VO2max) for 1 min followed by 2 min at 50% of VO2max. The control group received MICAT (n=31) at an intensity of 60% of VO2max in sessions of 36 min. RESULTS: patients had a mean age of 50.8±6.0 years, body mass index of 30.6±4.0 kg.m-2, body fat percentage of 38.7±7.0% and VO2max of 29.0±6.3 mL O2.kg-1.min-1; 70% were women. Compared to MICAT, HIIT-low volume was not superior in reducing Ln of IR (marginal mean difference: 0.083 [95% CI -0.092―0.257]; Cohen's d: 0.249; p value=0.346) or increasing Ln of total lean mass (kg) (0.004 [-0.014―0.023]; Cohen's d: 0.120; p=0.637) and Ln of thigh lean mass (g) (0.008 [-0,020―0.038]; Cohen's d: 0.154; p=0.599). After the intervention, the HIIT-low volume group, compared to the MICAT, had a higher HbA1c (5.81% vs 5.69%; 0.119 [0.005―0.233]; Cohen's d: 0.554; p=0.040). When comparing before and after the intervention, both training groups decreased IR. CONCLUSION: HIIT-low volume, compared to MICAT, is not superior in reducing IR or increasing skeletal muscle mass in adults with MS. Colciencias 111562638757; Interinstitucional 2016-13041; Doctoral scholarships 727-2015

Titin and CK2α are New Intracellular Targets in Acute Insulin Application-Associated Benefits on Electrophysiological Parameters of Left Ventricular Cardiomyocytes From Insulin-Resistant Metabolic Syndrome Rats.

Previous studies have demonstrated that a high-carbohydrate intake could induce metabolic syndrome (MetS) in male rats with marked cardiac functional abnormalities. In addition, studies mentioned some benefits of insulin application on these complications, but there are considerable disagreements among their findings. Therefore, we aimed to extend our knowledge on the in-vitro influence of insulin on left ventricular dysfunction and also in the isolated cardiomyocytes from MetS rats. At the organ function level, an acute insulin application (100-nM) provided an important beneficial effect on the left ventricular developed pressure in MetS rats. Furthermore, to treat the freshly isolated cardiomyocytes from MetS rats with insulin provided marked recoveries in elevated resting intracellular Ca2+-level, as well as significant prevention of prolonged action potential through an augmentation in depressed K+-channel currents. Insulin also normalized the cellular levels of increased ROS and phosphorylation of PKCα, together with normalizations of apoptotic markers in MetS cardiomyocytes through the insulin-mediated regulation of phospho-Akt. Since not only elevated PKCα-activity but also reductions in phospho-Akt are key modulators of titin-based cardiomyocyte stiffening in hyperglycemia, insulin treatment of the cardiomyocytes prevented the activation of titin via the above pathways. Furthermore, CK2α-activation and NOS-phosphorylation could be prevented with insulin treatment. Mechanistically, we found that impaired insulin signaling and elevated PKCα and CK2α activities, as well as depressed Akt phosphorylation, are key modulators of titin-based cardiomyocyte stiffening in MetS rats. We propose that restoring normal kinase activities and also increases in phospho-Akt by insulin can contribute marked recoveries in MetS heart function, indicating a promising approach to modulate titin-associated factors in heart dysfunction associated with type-2 diabetes mellitus. Graphical Abstract.