The crucial role and mechanism of insulin resistance in metabolic disease

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 28, 2023

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, nonalcoholic fatty liver disease, provides basis for common understanding these chronic diseases. In this study, we provide systematic review causes, mechanisms, treatments IR. The pathogenesis IR depends on genetics, obesity, age, drug effects. Mechanistically, any factor leading to abnormalities insulin signaling pathway leads host, including receptor abnormalities, disturbances internal environment (regarding inflammation, hypoxia, lipotoxicity, immunity), metabolic function organelles, other abnormalities. available therapeutic strategies are mainly exercise dietary habit improvement, chemotherapy based biguanides glucagon-like peptide-1, traditional Chinese medicine (e.g., herbs acupuncture) can also be helpful. Based current there still some vacancies follow up consider, is need define more precise biomarkers different lifestyle interventions, explore natural or synthetic drugs targeting treatment. This could enable treatment patients with multiple combined diseases, aim treating disease holistically reduce healthcare expenditures improve quality life extent.

Language: Английский

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Insulin Resistance: The Increased Risk of Cancers

Current Oncology, Journal Year: 2024, Volume and Issue: 31(2), P. 998 - 1027

Published: Feb. 13, 2024

Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction signaling to blood glucose levels. This state observed when muscle cells, adipose tissue, and liver improperly respond particular concentration insulin. resistance related increased plasma levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states in obesity type 2 diabetes mellitus. Observations cancer patients confirm that hyperinsulinemia major factor influencing obesity, diabetes, cancer. Obesity have been reported risks initiation, progression, metastasis several cancers. However, both aforementioned pathologies independently additionally increase risk. The disorders associated with poor outcomes treatment. For example, suffering from higher recurrence rates their overall survival reduced. In these associations between risk, an overview various pathogenic mechanisms play role development discussed.

Language: Английский

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Advances in the molecular mechanisms of statins in regulating endothelial nitric oxide bioavailability: Interlocking biology between eNOS activity and L-arginine metabolism

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116192 - 116192

Published: Jan. 22, 2024

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested reduce the risk cardiovascular events owing their pleiotropic effects on vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition smooth muscle cell proliferation. The major beneficial effect in maintaining homeostasis is induction nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) cells. mechanisms underlying increased eNOS activation well-established various fields, transcriptional post-transcriptional regulation, kinase-dependent phosphorylation protein-protein interactions. However, mechanism which affect metabolism L-arginine, a precursor biosynthesis, has rarely discussed. Autophagy, crucial for energy homeostasis, regulates functions, production angiogenesis, potential therapeutic target diseases. this review, addition summarizing molecular statins, we also discuss L-arginine.

Language: Английский

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Statins and risk of type 2 diabetes: mechanism and clinical implications

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 19, 2023

Statins are widely used to prevent cardiovascular disease events. Cardiovascular diseases and type 2 diabetes tightly connected since is a major risk factor for diseases. Additionally, often precede the development of diabetes. These two have common genetic environmental antecedents. effective in lowering However, they also important side effects, including an increased The first study reporting association statin treatment with was WOSCOPS trial (West Scotland Coronary Prevention Study) 2001. Other primary secondary prevention studies as well population-based confirmed original findings. purpose our review examine summarize most findings these describe mechanisms how statins increase

Language: Английский

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Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN

American Heart Journal, Journal Year: 2024, Volume and Issue: 274, P. 32 - 45

Published: May 4, 2024

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] increases high-density (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential lower atherogenic lipoproteins in patients atherosclerotic cardiovascular disease (ASCVD) heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment available maximally tolerated lipid-modifying therapies, addressing an unmet medical need patient population at risk for events. BROADWAY (NCT05142722) BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed examine efficacy, safety, tolerability of as adjunct dietary intervention therapies participants history ASCVD and/or underlying HeFH is not adequately controlled. The primary efficacy endpoint was percent change from baseline day 84. Other endpoints included changes Apo non-HDL-C, HDL-C, A1, Lp(a) triglycerides addition parameters evaluating tolerability, pharmacokinetics. also adjudicated assessment major adverse events, measurements glucose homeostasis, ambulatory blood pressure monitoring substudy. A total 2532 were 354 receive 10 mg placebo (2:1) 365 days follow-up through 35 after last dose. Results both anticipated 2024. These will provide safety data support use among elevated whom existing sufficiently effective well-tolerated.

Language: Английский

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Diabetic Cardiomyopathy—From Basics through Diagnosis to Treatment

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 765 - 765

Published: March 29, 2024

Diabetic cardiomyopathy (DCM) is the development of myocardial dysfunction in patients with diabetes despite absence comorbidities such as hypertension, atherosclerosis or valvular defect. The cardiovascular complications poorly controlled are very well illustrated by U.K. Prospective Diabetes Study (UKPDS), which showed a clear association between increasing levels glycated hemoglobin and heart failure (HF). incidence HF projected to increase significantly, why its proper diagnosis treatment so important. Providing appropriate therapy focusing on antidiabetic hypolipemic consideration pharmacotherapy for reduces risk CMD complications. Health-promoting changes made low-carbohydrate diet, regular exercise weight reduction also appear be important achieving outcomes. New hope therapies DCM offered novel methods using stem cells miRNA, which, however, require more thorough research confirm their efficacy.

Language: Английский

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Comparative Analysis of Adverse Event Profiles Among Seven Statins for Hypercholesterolemia Management Using the United States FDA Adverse Event Reporting System

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Background Statins are fundamental in hypercholesterolemia management, with seven primary drugs available: atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and pitavastatin. While sharing a common mechanism of action, these statins exhibit variations pharmacokinetic (what the body does to drug) pharmacodynamic drug body) properties (e.g., lipophilicity, cytochrome P450 metabolism), which may influence their safety profiles. Adverse events (AEs) such as myopathy hepatotoxicity vary across agents, complicating clinical decision-making. The guidelines lack robust comparisons all statins' AE profiles, presenting challenges for clinicians balancing potency tolerability. Objectives This study aimed comprehensively compare patterns profiles management through retrospective analysis United States Food Drug Administration Event Reporting System (FAERS) database. By focusing solely on hypercholesterolemia, we control potential confounding factors, providing more focused comparison statin Methods We conducted using data from FAERS between 2004 2024. To this included only patients prescribed clearly documented indication management. Patients other indications or missing reason prescription were excluded. Comparative evaluations employed reporting odds ratio (ROR) adjusted ROR (aROR), chosen efficiency ease interpretation, ability adjust compatibility statistical testing frameworks. allowed rigorous multiple analysis, where each was sequentially set reference 21 pairwise comparisons. address problem, applied Bonferroni correction, adjusting significance level 0.05 / = 0.0024. Patient background variables used adjustment factors aROR. AEs classified into 10 categories based characteristics. Results With atorvastatin reference, five (simvastatin, pitavastatin) demonstrated both significant > 1 aROR gastrointestinal disorders. Conversely, < metabolic When no consistent pattern exclusively observed categories. Instead, heterogeneous distribution outcomes evident. These results indicate that differ statin. Conclusions reveals distinct among statins, critical insights guide personalized treatment strategies. aligning patient risk specific can implement targeted approaches minimize AEs, potentially improving adherence efficacy. findings directly inform decision-making, enabling healthcare providers optimize selection individual patients.

Language: Английский

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The Effect of Statins on Clinical Outcome Among Hospitalized Patients With COVID-19: A Multi-Centric Cohort Study

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: July 5, 2022

The coronavirus disease-2019 (COVID-19) is caused by SARS-CoV-2, leading to acute respiratory distress syndrome (ARDS), thrombotic complications, and myocardial injury. Statins, prescribed for lipid reduction, have anti-inflammatory, anti-thrombotic, immunomodulatory properties are associated with reduced mortality rates in COVID-19 patients. Our goal was investigate the beneficial effects of statins hospitalized patients admitted three multi-specialty hospitals India from 1 June 2020, 30 April 2021. This retrospective study included 1,626 patients, which 524 (32.2%) were antecedent statin users among 768 (384 users, 384 non-statin users) identified 1:1 propensity-score matching. We established a multivariable logistic regression model identify patients' demographics adjust baseline clinical laboratory characteristics co-morbidities. Statin showed lower mean white blood cell count (7.6 × 103/µL vs. 8.1 103/µL, p < 0.01), C-reactive protein (100 mg/L 120.7 mg/L, 0.001) compared same positive results followed profiles on statins. Cox proportional-hazards models evaluated association between use rate. primary endpoint involved during hospital stay. odds propensity-matched cohort (OR 0.52, 95% CI 0.33-0.64, 0.001). These support previous evidence reducing

Language: Английский

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Clinical expert consensus on the assessment and protection of pancreatic islet β-cell function in type 2 diabetes mellitus

Diabetes Research and Clinical Practice, Journal Year: 2023, Volume and Issue: 197, P. 110568 - 110568

Published: Feb. 3, 2023

Islet β-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment islet function beneficial to better management T2DM. Protecting vital delay the progress mellitus. Therefore, Pancreatic Expert Panel Chinese Diabetes Society and Endocrinology Jiangsu Medical Association organized experts draft "Clinical expert consensus on protection pancreatic in mellitus." This suggests that can be clinically assessed using blood glucose-based methods or combine glucose endogenous insulin C-peptide levels. Some measures, including weight loss early sustained euglycemia control, could effectively protect function, some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor Glucagon-like peptide-1 receptor agonists, improve independent glycemic control.

Language: Английский

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A Comprehensive Review of the Vascular Consequences of Diabetes in the Lower Extremities: Current Approaches to Management and Evaluation of Clinical Outcomes

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 23, 2023

Diabetes mellitus is a global health concern characterized by chronic hyperglycemia, and its vascular consequences in the lower extremities pose significant challenges for individuals living with condition. This comprehensive review delves into multifaceted landscape of diabetes-related complications limbs, primary focus on current strategies management evaluation clinical outcomes. achieves several critical objectives synthesizing existing knowledge research findings. It elucidates intricate pathophysiological mechanisms underpinning these complications, shedding light cellular molecular processes involved. Additionally, it outlines assessment diagnostic used to identify stratify risk, ranging from cutting-edge imaging techniques examinations. The comprehensively examines strategies, encompassing lifestyle modifications, pharmacological interventions, surgical procedures, wound care practices. Moreover, assesses analyzes outcomes, including limb salvage rates, amputation overall quality life undergoing treatment. In addressing faced managing this aims contribute improved patient care. proposes future directions enhance outcomes extremities.

Language: Английский

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