Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study

The Lancet Healthy Longevity, Journal Year: 2022, Volume and Issue: 4(1), P. e23 - e33

Published: Dec. 12, 2022

BackgroundThe triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, important pathway in the development type 2 diabetes and cardiovascular diseases. However, association TyG with diseases mortality has mainly been investigated Asia, few data available from other regions world. We assessed resistance (as determined by index) individuals five continents at different levels economic development, living urban or rural areas. also examined whether associations differed according to country's economical development.MethodsWe used as a measure for resistance. Fasting triglycerides fasting plasma were measured baseline visit 141 243 aged 35–70 years 22 countries Prospective Urban Rural Epidemiology (PURE) study. The was calculated Ln (fasting [mg/dL] x [mg/dL]/2). hazard ratios (HRs) using multivariable Cox frailty model random effects test between risk mortality. primary outcome this analysis composite major events (defined death causes, non-fatal myocardial infarction, stroke). Secondary outcomes non-cardiovascular mortality, all infarctions, stroke, incident diabetes. did subgroup analyses examine magnitude (ie, income level countries.FindingsDuring median follow-up 13·2 (IQR 11·9–14·6), we recorded 6345 events, 2030 deaths, 3038 cases 3291 5191 After adjusting variables, developing increased across tertiles index. Compared lowest tertile index, highest (tertile 3) associated greater incidence (HR 1·21; 95% CI 1·13–1·30), infarction (1·24; 1·12–1·38), stroke (1·16; 1·05–1·28), (1·99; 1·82–2·16). No significant seen In low-income (LICs) middle-income (MICs), hazards (LICs: HR 1·31; 1·12–1·54; MICs: 1·20; 1·11–1·31; pinteraction=0·01), 1·44; 1·15–1·80; 1·29; 1·06–1·56; 1·26; 1·10–1·45; pinteraction=0·08), 1·35; 1·02–1·78; 1·17; 1·05–1·30; pinteraction=0·19), 1·64; 1·38–1·94; 2·68; 2·40–2·99; pinteraction <0·0001). contrast, high-income countries, higher only (2·95; 2·25–3·87; <0·0001), but not mortality.InterpretationThe significantly future diabetes, suggesting that plays promoting role pathogenesis metabolic Potentially, LICs MICs might be explained vulnerability these populations presence resistance.FundingFull funding sources are listed end paper (see Acknowledgments).

Language: Английский

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Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress

World Journal of Diabetes, Journal Year: 2023, Volume and Issue: 14(3), P. 130 - 146

Published: March 15, 2023

Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development progression of type 2 diabetes (T2D). Beyond detrimental effects insulin resistance, inflammation oxidative stress have emerged as critical features T2D that define dysfunction. Predominant markers such C-reactive protein, tumor necrosis factor alpha, interleukin-1β consistently associated with failure preclinical models people T2D. Similarly, important stress, increased reactive oxygen species depleted intracellular antioxidants, consistent damage conditions Such illustrate a relationship between an abnormal inflammatory response generation during The current review explores clinical research on patho-logical implications Moreover, molecular relevant biomarkers involved this process discussed to divulge link Underpinning relevance review, systematic analysis evidence from randomized controlled trials is covered, potential therapeutic some commonly used antidiabetic agents modulating makers improve function.

Language: Английский

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Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Theranostics, Journal Year: 2022, Volume and Issue: 12(3), P. 1220 - 1246

Published: Jan. 1, 2022

Background: Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity metabolic co-morbidities challenging.Obesity induced chronic inflammation including brain hallmark of via gut-brain axis.The objective this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well inflammatory activity reverse HFD in mice.Methods: GELNs were isolated administrated orally into fed mice.GaELNs fluorescent labeled for monitoring their vivo trafficking route after oral administration quantified number particles several tissues.The determined by measuring cytokines ELISA real-time PCR.Mitochondrial membrane permeability microglial cells using JC-10 fluorescence dye.The apoptotic cell death TUNEL assay.The metabolites identified LC-MS analysis.Memory function mice memory functional analysis.The effect GaELNs on glucose insulin response tolerance tests.c-Myc localization interaction with BASP1 calmodulin confocal microscopy.Results: Our results show preferentially taken up inhibits mice.GaELN phosphatidic acid (PA) (36:4) required uptake BASP1.Formation GaELNs/BASP1 complex inhibition c-Myc mediated expression STING.GaELN PA binds BASP1, leading through competitively binding CaM transcription factor.Inhibition STING leads reducing an array IFN-γ TNF-α.IFN-γ induces IDO1, which turn generated IDO1 dependent manner activate AHR pathway contributes developing obesity.The derived from treated promote neuronal differentiation mitochondrial death.GaELNs showed improved increased sensitivity these mice.Conclusion: Collectively, demonstrate how healthy diet can unhealthy high-fat reveal link between microglia/diet disease outcomes diet-derived nanoparticles.

Language: Английский

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Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review)

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(6)

Published: April 9, 2024

Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co‑morbidities, including type‑2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non‑alcoholic fatty liver disease, kidney respiratory disorders, sleep apnea, musculoskeletal disorders osteoarthritis, subfertility, psychosocial problems certain types cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro‑inflammatory polarization macrophages toward M1 phenotype, in adipose tissue (AT), subsequent increased production cytokines adipokines, inducing therefore an overall, systemic, low‑grade inflammation, which contributes syndrome (MetS), insulin resistance (IR) T2DM. Targeting mediators could be alternative therapies treat obesity, but their safety efficacy remains studied further confirmed future clinical trials. present review highlights molecular pathophysiological by chronic inflammation AT reactive oxygen species lead MetS, IR In addition, focus is given on role anti‑inflammatory agents, resolution through blockade chemotactic factors, such as monocytes chemotractant protein‑1, and/or mediators, IL‑1β, TNF‑α, visfatin, plasminogen activator inhibitor‑1, synthesis adiponectin apelin, obesity‑associated dysfunction.

Language: Английский

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Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 70, P. 102519 - 102519

Published: March 11, 2024

Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence IF its impact specific while evaluating quality.

Language: Английский

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A novel machine learning approach for diagnosing diabetes with a self-explainable interface

Healthcare Analytics, Journal Year: 2024, Volume and Issue: 5, P. 100301 - 100301

Published: Jan. 21, 2024

This study introduces the first-ever self-explanatory interface for diagnosing diabetes patients using machine learning. We propose four classification models (Decision Tree (DT), K-nearest Neighbor (KNN), Support Vector Classification (SVC), and Extreme Gradient Boosting (XGB)) based on publicly available dataset. To elucidate inner workings of these models, we employed learning interpretation method known as Shapley Additive Explanations (SHAP). All exhibited commendable accuracy in with diabetes, XGB model showing a slight edge over others. Utilising SHAP, delved into model, providing in-depth insights reasoning behind its predictions at granular level. Subsequently, integrated SHAP's local explanations an to predict patients. serves critical role it diagnoses offers transparent decisions made, users heightened awareness their current health conditions. Given high-stakes nature medical field, this developed can be further enhanced by including more extensive clinical data, ultimately aiding professionals decision-making processes.

Language: Английский

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Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes

Nutrients, Journal Year: 2024, Volume and Issue: 16(7), P. 1015 - 1015

Published: March 30, 2024

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance in various tissues. Though conventionally associated with obesity, current research indicates that visceral adipose tissue (VAT) the leading determining factor, wielding more influence regardless of individual body mass. The heightened activity VAT encourages circulation free fatty acid (FFA) molecules, which induce surrounding Individuals most vulnerable to this preferential fat deposition are older males ancestral ties Asian countries because genetics and sex hormones pivotal factors for accumulation. However, interventions one's diet lifestyle have potential strategically discourage growth VAT. This illuminates possibility expansion and, subsequently, risk T2D development preventable. Therefore, reducing amount accumulated an preventing it from building up, one can effectively control prevent T2D.

Language: Английский

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Timing of Moderate to Vigorous Physical Activity, Mortality, Cardiovascular Disease, and Microvascular Disease in Adults With Obesity

Diabetes Care, Journal Year: 2024, Volume and Issue: 47(5), P. 890 - 897

Published: April 9, 2024

To assess the association between timing of aerobic moderate to vigorous physical activity (MVPA) and risk cardiovascular disease (CVD), microvascular (MVD), all-cause mortality in adults with obesity a subset type 2 diabetes (T2D).

Language: Английский

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Cytokines as Key Players in Obesity Low Grade Inflammation and Related Complications

Obesity Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100585 - 100585

Published: Jan. 1, 2025

Language: Английский

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The role of M1/M2 macrophage polarization in the pathogenesis of obesity-related kidney disease and related pathologies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Obesity is a rapidly growing health problem worldwide, affecting both adults and children increasing the risk of chronic diseases such as type 2 diabetes, hypertension cardiovascular disease (CVD). In addition, obesity closely linked to kidney (CKD) by either exacerbating diabetic complications or directly causing damage. Obesity-related CKD characterized proteinuria, lipid accumulation, fibrosis glomerulosclerosis, which can gradually impair function. Among immune cells innate adaptive response involved in pathogenesis obesity-related diseases, macrophages play crucial role inflammation associated with CKD. obese individuals, enter pro-inflammatory state known M1 polarization, contributes inflammation. This polarization promotes tissue damage, fibrosis, leading progressive loss macrophage-induced oxidative stress key feature it also cell damage Macrophages contribute insulin resistance diabetes releasing inflammatory molecules that glucose metabolism, complicating management patients. Hypertension atherosclerosis, are often obesity, progression via pathways. influence blood pressure regulation vascular inflammation, particularly renin-angiotensin system. accumulate arterial plaques, plaque instability, may increase CVD review focuses on involvement highlights their critical link between other pathologies. Targeting macrophage ensuing could be an effective therapeutic strategy for related improve outcomes patients disease.

Language: Английский

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