Dysfunction In Metabolic Syndrome Research Articles

Molecular Adaptation of Cardiac Remodeling in Metabolic Syndrome: Focus on AMPK, SIRT1 and PGC-1a

Obesity, lack of physical activity, and genetic predisposition might play a pivotal role in pathogenesis of metabolic syndrome. Cardiac function alteration including hemodynamic changes, contractility function, arrhythmia, and cellular respiratory function, might happen due to chronic condition in metabolic syndrome. Insulin resistance, neurohormonal activation and chronic inflammation might contribute to these changes. Cardiomyocyte had capabilities to adapt from these abnormalities, one of them is the activation of cellular pathway to resist cardiac injury from metabolic syndrome. This molecular pathway involves three proteins, including AMP-activated protein kinase (AMPK), sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-α (PGC-1α). The aim of this narrative review is to elucidate role of AMPK, SIRT1, and PGC-1α in cardiac adaptation against cardiac dysfunction in metabolic syndrome. AMPK, SIRT-1, and PGC-1α contribute to adapt and to repair the cardiac injury resulting from celullar and mechanical stress from metabolic syndrome and prevent cardiac remodeling event. Several pathological events, such as insulin resistance, induce alteration of switching energy fuel to the heart, causing cardiomyocte to rely on glucose metabolism and lipotoxicity, leading to damages of cardiomyocyte through reactive oxygen species (ROS) generation and lipid peroxidation. Increase of ROS promotes cardiac injury followed by necrotic and apoptotic events. AMPK, SIRT1, and PGC-1α act as cardioprotector molecule against metabolic syndrome insults to several mechanism such as: AMPK play role as counter act of lipotoxicity and insulin resistance through increasing insulin sensitivity and regulate redox reaction. SIRT1 plays role in regulating apoptotic genes and PGC-1α repairs cardiac fuel sources. Activation of AMPK/SIRT1/PGC-1α prevent cardiac remodeling due to metabolic syndrome by increasing insulin sensitivity, increases mitochondrial biogenesis and reduce pro-apoptotic signals in cardiomyocte.Keywords: AMPK/SIRT1/PGC-α, cardiac remodeling, metabolic syndrome

Revealing Left Atrial Dysfunction in Metabolic Syndrome and Atrial Fibrillation

Revealing Left Atrial Dysfunction in Metabolic Syndrome and Atrial Fibrillation

Association of Helicobacter Pylori Infection with Endothelial Dysfunction in Metabolic Syndrome

Background: Metabolic risk factors play a critical role in metabolic syndrome (MetS), and endothelial dysfunction is important in its development. On the other hand, Helicobacter pylori (H. pylori) infection has an essential role in MetS. The goal of present study was to evaluate the effect of H. pylori infection on endothelial dysfunction in MetS patients.
 Methods: Based on the International Diabetes Federation (IDF) criteria, 80 MetS patients (59 females and 21 males, mean age: 48.94 ± 10.00 years) were selected. Plasma samples were assayed for H. pylori IgG using the ELISA method. Endothelial function was also evaluated by measuring plasma concentrations of endothelin-1 (ET- 1), E-selectin, and intracellular adhesion molecule (ICAM-1) using ELISA method. Also, NO2 −− and NO3 −− concentrations were measured by Griess method.
 Results: Fifty patients (62.5%) had H. pylori infection. Plasma concentrations of ET-1, NO2−−, and NO3−− were significantly higher in MetS patients with positive H. pylori infection than in MetS patients with negative H. pylori infection (ET-1: 2.92 ± 2.33 vs 1.9 ± 1.4 pg/ml; P = 0.037; NO2 −−:19.46 ± 7/11 vs 15.46 ± 4.56 μM; P = 0.003; NO3 −−: 20.8 ± 10.53 vs 16.85 ± 6.03 μM, P = 0.036). However, plasma concentrations of ICAM-1 and E-selectin did not show any significant difference in the two groups.
 Conclusion: The results showed a relationship between H. pylori infection and endothelial dysfunction. Helicobacter pylori infection can lead to atherosclerosis by causing chronic inflammation and affecting the factors contributing to the MetS.

PS-B01-2: ASSOCIATION BETWEEN IMPAIRED METABOLIC FUNCTION AND VASCULAR DYSFUNCTION IN METABOLIC SYNDROME

Objectives: Metabolic syndrome is a leading cause for vascular dysfunction and cardiovascular diseases. We have previously shown that vascular functional responses in metabolic syndrome exhibit exaggerated vasocontractility and impaired endothelium-dependent relaxation. However, it remains unclear if a correlation between vascular abnormalities and metabolic disturbances exists. Accordingly, we aimed to explore the association between vascular dysfunction and changes in metabolic parameters in a rodent model of metabolic syndrome, the high fat diet (HFD)-streptozotocin (STZ)-induced diabetes mellitus rat (HFD-D). Design and method: Five weeks old male Wistar albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. On week 6, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, metabolic data were collected then rats were euthanized for blood and kidney collection and to measure maximal vasoconstrictor and vasodilator responses of the abdominal aortic rings. Recorded measures also included fasting blood glucose (FBG), plasma total cholesterol (TC), plasma triglyceride (TG), plasma high density lipoprotein (HDL), plasma creatinine (Cr), urinary protein: urinary creatinine (UPC) and kidney index (KI). Results: HFD-D rats had higher FBG, TG, Cr, UPC, and KI compared with controls. HDL was lower in HFD-D while TC remained unchanged. Maximal vasoconstriction to norepinephrine (NE Rmax) was greater in the HFD group compared with controls. Maximal endothelium-dependent vasorelaxation to acetylcholine (ACh Rmax) was blunted in the HFD group relative to controls. A positive correlation between NE Rmax and FBG was found, whereas ACh Rmax was negatively correlated with FBG, KI, UPC and TG. Conclusions: Impaired glucose metabolism, lipid profile and renal function are likely key contributors to vascular dysfunction in metabolic syndrome; however, further mechanistic investigations are required to verify these assumptions.

Cinnamaldehyde Supplementation Reverts Endothelial Dysfunction in Rat Models of Diet-Induced Obesity: Role of NF-E2-Related Factor-2.

Cinnamaldehyde (CN) is an activator of NF-E2-related factor 2 (Nrf2), which has the potential to reduce endothelial dysfunction, oxidative stress and inflammation in metabolic disorders. Our main purpose was to evaluate the effects of CN on vascular dysfunction in metabolic syndrome rats. Normal Wistar (W) rats were divided into eight groups: (1) Wistar (W) rats; (2) W rats fed with a high-fat diet (WHFD); (3) W rats fed with a sucrose diet (WS); (4) WHFD fed with a sucrose diet (WHFDS); (5) W treated with CN (WCn); (6) WS treated with CN (WSCn); (7) WHFD treated with CN (WHFDCn); (8) WHFDS treated with CN (WHFDSCn). CN treatment with 20 mg/kg/day was administered for 8 weeks. Evaluation of metabolic profile, inflammation, endothelial function, oxidative stress, eNOS expression levels and Nrf2 activation was performed. The metabolic dysfunction was greatly exacerbated in the WHFDS rats, accompanied by significantly higher levels of vascular oxidative stress, inflammation, and endothelial dysfunction. In addition, the WHFDS rats displayed significantly reduced activity of Nrf2 at the vascular level. CN significantly reverted endothelial dysfunction in the aortas and the mesenteric arteries. In addition, CN significantly decreased vascular oxidative damage, inflammation at vascular and perivascular level and up-regulated Nrf2 activity in the arteries of WHFDS rats. Cinnamaldehyde, an activator of Nrf2, can be used to improve metabolic profile, and to revert endothelial dysfunction in obesity and metabolic syndrome.

Modulatory effect of filarial infection on the systemic hormone levels in subjects with metabolic syndrome (DM-LF5).

Metabolic syndrome (MS) refers to a group of co-morbidities which include central obesity, hypertension, hyperglycemia and dyslipidemia. Previously, we reported that childhood lymphatic filariasis (LF) confers significant protection against type-1 and type-2 forms of diabetes, by means of immunomodulation. In the present study, we studied the effect of LF on endocrine dysfunction in MS and Non-MS patients in baseline and after 10 years of follow-up. We quantified the serum levels of pancreatic hormones (insulin and glucagon), incretins (Ghrelin, GIP and GLP-1) and adipokines (leptin, adiponectin, adipsin, visfatin, PAI-1 and resistin) by multiplex bead array system. MS (both LF- and LF+) subjects had increased insulin levels compared to NMS (both LF- and LF+) subjects. MS-LF+ subjects had significantly increased levels of glucagon, ghrelin, GIP and GLP-1 and decreased levels of adipsin, compared to MS-LF- subjects. Interestingly this effect was short-lived and was not seen in the follow-up samples. Overall, LF infection might confer limited short-term beneficial effects against MS, by means of modulating the incretin levels,either directly or indirectly.

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes.

Obesity, type 2 diabetes, and their associated comorbidities impact brain metabolism and function and constitute risk factors for cognitive impairment. Alterations to taurine homeostasis can impact a number of biological processes, such as osmolarity control, calcium homeostasis, and inhibitory neurotransmission, and have been reported in both metabolic and neurodegenerative disorders. Models of neurodegenerative disorders show reduced brain taurine concentrations. On the other hand, models of insulin-dependent diabetes, insulin resistance, and diet-induced obesity display taurine accumulation in the hippocampus. Given the possible cytoprotective actions of taurine, such cerebral accumulation of taurine might constitute a compensatory mechanism that attempts to prevent neurodegeneration. The present article provides an overview of brain taurine homeostasis and reviews the mechanisms by which taurine can afford neuroprotection in individuals with obesity and diabetes. We conclude that further research is needed for understanding taurine homeostasis in metabolic disorders with an impact on brain function.

COVID-19 and metabolic syndrome

Abstract BACKGROUND: Metabolic syndrome (MS) and its components contribute to severe and worse outcomes of COVID-19. We aimed to describe the impact of MS on COVID-19 infection. PATIENTS AND METHODS: A retrospective study, including COVID-19 patients, hospitalized in the infectious diseases department in Hedi Chaker Hospital between November 2020 and February 2021. The population was divided into G1 (with MS) and G2 (without MS). MS has been defined by the co-occurrence of three of these cardiovascular risk factors (insulin resistance, obesity, atherogenic dyslipidemia and hypertension). RESULTS: In total, 351 patients were collected. The main cardiovascular risk factors were diabetes (43.5%), high blood pressure (43.8%), stroke (12.8%), dyslipemia (9.4%), and obesity (15.9%). The population was divided into G1 (111 patients) and G2 (241 patients). G1 patients were older: 68 ± 11(p = 0.009). There was no difference in terms of gender (p=0.4). Smoking was found similarly (p = 0.1). Dyspnea and digestive manifestations were observed in both groups (p 0.4 and 0.6 respectively). Cough was more reported in G1 patients (p=0.03). Severe forms (> 10L / min of oxygen therapy) were more observed in G1 (p = 0.03). Acute renal failure was more observed in G1 (p=0.007). Cytolysis were found on both groups. Transfer to intensive care and death were independent of MS (p 0.1 and 0.3, respectively). CONCLUSION: Based on our results, MS is associated with advanced age and leaded to severe forms. In fact, pre-existing endothelial dysfunction in MS may play a crucial role for the development of severe COVID-19. Funding and Conflicts of Interest No

Thyroid dysfunction in patients of metabolic syndrome: A study from a tertiary care center in India

Background: Metabolic syndrome is characterized by hypertension, dyslipidemia, central obesity, glucose intolerance, insulin resistance. Thyroid hormone acts as general pacemaker, accelerating metabolic process and may be associated with metabolic syndrome. There is no information available in literature regarding the prevalence and association of thyroid dysfunction in metabolic syndrome in this central region of the country. Aims and Objective: To estimate the prevalence of thyroid dysfunction in patients of metabolic syndrome. Materials and Methods: It is a duration based prospective cross sectional study including 200 patients of metabolic syndrome. A detailed history, clinical examination and relevant investigations including serum Free T4 (FT4), Free T3 (FT3), Thyroid Stimulating Hormone (TSH) were done. Range, frequencies, percentage, mean, standard deviation and P value were calculated. P value of < 0.05 was taken as significant. Results: Prevalence of thyroid dysfunction in metabolic syndrome patients was 28.5%. Prevalence of subclinical and overt hypothyroidism was 18.5% and 8.5% respectively. In patients with both metabolic syndrome and thyroid dysfunction, most common components associated are diabetes mellitus and hypertriglyceridemia. Conclusion: Thyroid dysfunction is significantly common in metabolic syndrome patients. It should be aggressively detected and treated in these patients for better outcome.

PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits

Background and aimsUnderlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another. MethodsIn this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis. ResultsMetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodilation was affected in both arteries in a different way. The aorta from MetS showed vascular dysfunction, including lower response to acetylcholine and sodium nitroprusside, while the renal artery from MetS presented a preserved relaxation to acetylcholine and an increased sensitivity to sodium nitroprusside. We did not find vascular oxidative stress in the aorta from MetS, but we found a significant decrease in PPARγ, phospho-Akt (p-Akt) and phospho-eNOS (p-eNOS) protein expression. On the other hand, we found oxidative stress in the renal artery from MetS, and PPARγ, Akt and p-Akt were overexpressed. No evidence of atherosclerosis was found in arteries from MetS. ConclusionsMetS affects vascular function differently depending on the vessel. In the aorta, it decreases both the vasodilation and the expression of the PPARγ/Akt/eNOS pathway, while in the renal artery, it increases the expression of PPARγ/Akt signalling pathway without decreasing the vasodilation.

Berberine ameliorates endothelial dysfunction in metabolic syndrome

Background and Aims: The metabolic syndrome is considered a chronic inflammatory state which augments endothelial dysfunction and leads to cardiovascular ischemic events and increase in mortality. It is characterized by a low nitric oxide (NO) bioavailability, endothelial dysfunction together with hyperglycaemia, dyslipidaemia, oxidative stress and insulin resistance and precede the early conditions involved in the genesis of macrovascular disorders. Berberine is a natural alkaloid found in rhizomes and roots of a variety of plants. Initially used as a detoxicating and anti-inflammatory agent in traditional Chinese medicine. The main aim of this work was to investigate the potential of berberine as a therapeutic approach to endothelial dysfunction in metabolic syndrome induced by high fat diet in non-obese Sprague-Dawley rats (SD).

Regional functional and structural abnormalities within the aorta as a potential driver of vascular disease in metabolic syndrome.

What is the central question of this study? Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta? What is the main finding and its importance? Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome. The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high-fat diet (HFD) streptozotocin-induced diabetes mellitus (HFD-D). Four-week-old male Wistar albino rats were fed with either HFD or control diet (CD) for 10weeks. At week6, 40mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail-cuff systolic blood pressures (154±6vs. 110±4mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD-D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD-D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD-D group. Abdominal, but not thoracic, endothelium-dependent vasorelaxation in response to acetylcholine was blunted in HFD-D relative to CD rats; however, nitric oxide-dependent vasorelaxation in HFD-D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD-D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

Peculiarities of cardiac remodeling and myocardial dysfunction in metabolic syndrome

Introduction. In 2016, updated recommendations for echocardiographic diagnosis of diastolic dysfunction were developed. It requires a review of the degree of metabolic syndrome (MS) influence on the heart and blood vessels remodeling and the development of left ventricle (LV) diastolic dysfunction (DD).Purpose. Assessment of the MScontribution to the heart and blood vessels remodeling, as well as to the development of LVDD with an analysis of the LV remodeling types and the degree of LVDD.Materials and methods. The main group: 130 patients with MS (62 (47,7%) — men, 68 (52,3%) — women; average age — 59,8±9,5 years) who underwent in-patient examination and treatment in the cardiology department for arterial hypertension (AH) in 2015-2017. The control group included 36 patients with AH (18 (50%) — men, 18 (50%) — women; average age — 56,0±12,7 years) without abdominal obesity, not meeting the criteria of MS International Diabetes Federation.Results. MS is associated with increased prevalence of adverse LV remodeling and DD. In MS group concentric LV hypertrophy was detected significantly commoner than in group without MS, in which concentric remodeling was the most frequent structural abnormality. Eccentric LV hypertrophy was diagnosed only in pts with so-called complete MS. Moreover DD was detected in all pts with complete MS. Type 2 DD was present predominantly in subgroup with complete MS, reflecting relationship between the degree of LV DD and severity of MS in AH pts.Conclusions. Obtained results confirm adverse influence of central obesity and MS on LV myocardial structure and function.

Impaired baroreflex sensitivity and cardiac autonomic functions are associated with cardiovascular disease risk factors among patients with metabolic syndrome in a tertiary care teaching hospital of South-India

Background & aimBaroreflex sensitivity (BRS) and heart rate variability (HRV) have been proposed to assess early autonomic dysfunction in metabolic syndrome (MetS) patients. Autonomic dysfunction in MetS patients may increase the risk of developing cardiovascular disease (CVD). However, the association of BRS and HRV with CVD risk factors remains elusive in MetS. The primary aim of this study was to assess the BRS and HRV in MetS patients among South-Indian adults and check whether BRS and HRV are associated with CVD risk factors. MethodsWe performed anthropometric indices, body composition, physiological parameters such as BRS, HRV, and other autonomic function tests in 176 subjects divided into MetS patients (n = 88) and healthy controls (n = 88). Fasting blood samples were collected for biochemical profiles and calculated insulin resistance indices, atherogenic index (AI), and rate pressure product (RPP). ResultsWhen compared to controls, we found significantly reduced BRS and an increased ratio of low-frequency (LF) to high-frequency (HF) power of HRV (LF/HF) in the MetS group. We observed significant differences in body composition and biochemical profiles among the MetS group. BRS and LF/HF ratio of HRV have shown a significant association with CVD risk factors in the MetS group. ConclusionsWe observed autonomic dysfunction as low BRS and high LF/HF ratio of HRV in MetS patients. Additionally, the present results emphasize that the association of BRS and LF/HF ratio with anthropometric, glucose, lipid parameters, and other CVD risk factors may increase the susceptibility of MetS patients to higher CVD risk.

Association Between Subclinical Left Ventricular Myocardial Systolic Dysfunction Detected by Strain and Strain‑Rate Imaging and Liver Steatosis and Fibrosis Detected by Elastography and Controlled Attenuation Parameter in Patients with Metabolic Syndrome.

PurposeThe components of metabolic syndrome (MS) are risk factors for developing both cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Strain (SI) and strain‑rate imaging (SRI) are able to recognize early changes in cardiac function. Vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) detect and quantify liver fibrosis and steatosis. We aimed to assess whether there is any correlation between liver fibrosis and steatosis and left ventricular (LV) dysfunction in MS patients.Patients and MethodsA total of 150 adults with MS were registered in the study. They were compared with a control group of 150 age- and sex-matched adults without MS. After the classic echocardiographic assessment of LV function, two-dimensional speckle echocardiography (2D-STE) was used to evaluate LV peak systolic strain (S) and peak systolic strain rate (SR), while liver steatosis and fibrosis were evaluated by VCTE and CAP.ResultsLV diastolic dysfunction was significantly more frequent among the patients with MS. We found significant differences between the two groups regarding the presence of subtle LV systolic dysfunction, detected by reduced values of S and SR. The risk for LV diastolic dysfunction was 3.6 times higher in MS with severe steatosis and 8 times higher in patients with severe fibrosis, P<0.0001. The risk for LV systolic dysfunction was double in MS with severe steatosis and 1.7 times higher in MS with severe fibrosis, P<0.0001.ConclusionIn MS patients with normal LV ejection fraction, conventional echocardiography parameters identified diastolic LV dysfunction, while SI and SRI identified subtle impairment of systolic LV dysfunction. The presence of hepatic steatosis and fibrosis increases significantly the risk for cardiac dysfunction in MS patients (P<0.0001).

Prevalence of thyroid dysfunction in metabolic syndrome - A cross-sectional study

Literature review have hypothesized that the rising incidence of metabolic syndrome worldwide has been associated with an increased risk of thyroid disorders. The aim &amp; objective of our study was to diagnose patients with metabolic syndrome based on IDF criteria, to estimate T3, T4, TSH levels among these patients and to observe the correlation between thyroid dysfunction and metabolic syndrome.Our study was a hospital based age and sex matched cross-sectional study with a total of 120 participants (60 cases and 60 controls) between 30 - 50 years old conducted at Malla Reddy Institute of Medical Sciences, Hyderabad, India. Ethics approval was obtained from the Institutional Ethics Committee.Our study found that both men and women with metabolic syndrome had a higher percentage of thyroid disorders compared to the controls without metabolic syndrome. Among the cases, women were found to present with more thyroid abnormalities than men.Routine screening with thyroid function tests should be implemented for all patients with metabolic syndrome, especially females. The coexistence of these two entities can increase the risk for cardiovascular disease. Early detection and intervention can help reduce the progression of CVD.

Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease 2019.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 infection is a serious global concern. Increased morbidity and mortality is associated with older age, male gender, cardiovascular disease, diabetes, and smoking. As COVID-19 spreads from coastal borders, both state to state and country to country, our understanding of its pathophysiology has evolved. Age and type 2 diabetes mellitus (T2DM) play especially important roles in COVID-19 progression. T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling. COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases. Unmasking existing vulnerabilities in diabetic patients with COVID-19 is important. Globally, we must come together to better understand why T2DM is associated with increased COVID-19 morbidity and mortality.

Study of thyroid dysfunction in metabolic syndrome in patients of Amalapuram, Andhra Pradesh, India

Background: Both metabolic syndrome and thyroid dysfunction are associated with increased risk of atherosclerotic heart disease. The present study was conducted to study the Association of thyroid dysfunction and Metabolic syndrome and to find out the type of thyroid dysfunction in metabolic syndrome patients.Methods: Sixty cases were defined according to the IDF Criteria. Detailed history and necessary investigations like fasting blood sample was analyzed for total triiodothyronine (T3), total thyroxine (T4), thyroid-stimulating hormone (TSH), lipid profile, and blood glucose were undertaken.Results: In this study population of metabolic syndrome cases, the thyroid dysfunction is present in 16.7% patients. Among the thyroid dysfunction, sub clinical hypothyroidism is highly prevalent - 11.7%, The hypothyroidism is 3.3% prevalent in metabolic syndrome patients (one patient had TSH levels of more than 150 mU/L) and sub clinical hyperthyroidism is 1.7% prevalent. There were no overt hyperthyroidism patients in the study.Conclusions: This study clearly shows that, one sixth of metabolic syndrome patients or every sixth metabolic syndrome had hypothyroidism either overt or subclinical. This finding indicates a need for investigating the presence of Thyroid dysfunction during managing metabolic syndrome patients

The contribution of chymase-dependent formation of ANG II to cardiac dysfunction in metabolic syndrome of young rats: roles of fructose and EETs.

The roles of ACE-independent ANG II production via chymase and therapeutic potential of epoxyeicosatrienoic acids (EETs) in fructose-induced metabolic syndrome (MetS) in the adolescent population remain elusive. Thus we tested the hypothesis that a high-fructose diet (HFD) in young rats elicits chymase-dependent increases in ANG II production and oxidative stress, responses that are reversible by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), an inhibitor of soluble epoxide hydrolase (sEH) that metabolizes EETs. Three groups of weanling rats (21-day-old) were fed a normal diet, 60% HFD, and HFD with TPPU, respectively, for 30 days. HFD rats developed MetS, characterized by hyperglycemia, hyperinsulinemia, and hypertension and associated with decreases in cardiac output and stroke volume and loss of nitric oxide (NO) modulation of myocardial oxygen consumption; all impairments were normalized by TPPU that significantly elevated circulating 11,12-EET, a major cardiac EET isoform. In the presence of comparable cardiac angiotensin-converting enzyme (ACE) expression/activity among the three groups, HFD rats exhibited significantly greater chymase-dependent ANG II formation in hearts, as indicated by an augmented cardiac chymase content as a function of enhanced mast cell degranulation. The enhanced chymase-dependent ANG II production was paralleled with increases in ANG II type 1 receptor (AT1R) expression and NADPH oxidase (Nox)-induced superoxide, alterations that were significantly reversed by TPPU. Conversely, HFD-induced downregulation of cardiac ACE2, followed by a lower Ang-(1-7) level displayed in an TPPU-irreversible manner. In conclusion, HFD-driven adverse chymase/ANG II/Nox/superoxide signaling in young rats was prevented by inhibition of sEH via, at least in part, an EET-mediated stabilization of mast cells, highlighting chymase and sEH as therapeutic targets during treatment of MetS.NEW & NOTEWORTHY As the highest fructose consumers, the adolescent population is highly susceptible to the metabolic syndrome, where increases in mast cell chymase-dependent formation of ANG II, ensued by cardiometabolic dysfunction, are reversible in response to inhibition of soluble epoxide hydrolase (sEH). This study highlights chymase and sEH as therapeutic targets and unravels novel avenues for the development of optimal strategies for young patients with fructose-induced metabolic syndrome.