The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review

Hepatology, Journal Year: 2023, Volume and Issue: 77(4), P. 1335 - 1347

Published: Jan. 3, 2023

Background and Aims: NAFLD is a leading cause of liver-related morbidity mortality. We assessed the global regional prevalence, incidence, mortality using an in-depth meta-analytic approach. Approach Results: PubMed Ovid MEDLINE were searched for population-based studies from 1990 to 2019 survey year (last published 2022) per Preferred Reporting Items Systematic Reviews Meta-Analyses (PRISMA). Meta-analysis was conducted random-effects models. Bias risk assessment Joanna Briggs Institute. Of 2585 reviewed, 92 (N=9,361,716) met eligibility criteria. Across study period (1990–2019), pooling prevalence estimates ultrasound-defined yielded overall 30.05% (95% CI: 27.88%–32.32%) 30.69% (28.4–33.09), respectively. Global increased by +50.4% 25.26% (21.59–29.33) in 1990–2006 38.00% (33.71–42.49) 2016–2019 ( p <0.001); +38.7% 25.16% (19.46–31.87) 34.59% (29.05–40.57) =0.029). The highest Latin America 44.37% (30.66%–59.00%), then Middle East North Africa (MENA) (36.53%, 28.63%–45.22%), South Asia (33.83%, 22.91%–46.79%), South-East (33.07%, 18.99%–51.03%), (31.20%, 25.86%–37.08%), (29.71%, 25.96%–33.76%), Pacific 28.02% (24.69%–31.60%), Western Europe 25.10% (20.55%–30.28%). Among cohort diagnosed without liver biopsy, pooled rate 1000 PY 12.60 (6.68–23.67) all-cause mortality; 4.20 (1.34–7.05) cardiac-specific 2.83 (0.78–4.88) extrahepatic cancer-specific 0.92 (0.00–2.21) liver-specific Conclusions: 30% increasing which requires urgent comprehensive strategies raise awareness address all aspects on local, regional, levels.

Language: Английский

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Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 21 - 42

Published: Feb. 13, 2023

Abstract Proliferative diabetic retinopathy (PDR) the sequel of (DR), a frequent complication diabetes mellitus (DM), is leading cause blindness in working-age population. The current screening process for DR risk not sufficiently effective such that often disease undetected until irreversible damage occurs. Diabetes-associated small vessel and neuroretinal changes create vicious cycle resulting conversion into PDR with characteristic ocular attributes including excessive mitochondrial retinal cell damage, chronic inflammation, neovascularisation, reduced visual field. considered an independent predictor other severe complications as ischemic stroke. A “domino effect” highly cascading DM which early indicator impaired molecular signaling. Mitochondrial health control clinically relevant management, multi-omic tear fluid analysis can be instrumental prognosis prediction. Altered metabolic pathways bioenergetics, microvascular deficits disease, tissue remodelling are focus this article evidence-based targets predictive approach to develop diagnosis treatment algorithms tailored individual cost-effective prevention by implementing paradigm shift from reactive medicine predictive, preventive, personalized (PPPM) primary secondary care management.

Language: Английский

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Dietary Polyphenols as Natural Inhibitors of α-Amylase and α-Glucosidase

Life, Journal Year: 2022, Volume and Issue: 12(11), P. 1692 - 1692

Published: Oct. 25, 2022

It is well known that carbohydrates are the main source of calories in most diets. However, by inhibiting carbohydrases, intake reduced and weight loss improved. α-amylase an enzyme hydrolyses α-1,4 glycosidic linkages α-linked polysaccharides, resulting low-molecular-weight products such as glucose, maltose maltotriose, while α-glucosidase catalyzes hydrolysis nonreducing α-1,4-linked glucose moieties from disaccharides or oligosaccharides. Currently, one common nutritional disorders world hyperglycemia. One new therapeutic approaches to treat this disease application natural inhibitors, polyphenols, control starch digestion regulate blood level. Dietary polyphenols showed potential inhibitory activity against review summarizes recently published literature studied inhibition mechanisms structure–activity relationship between individual dietary mentioned digestive enzymes. higher binding interactions cause activities; thus, different can affect steps polysaccharides. The aim clarify these introduce polyphenol-rich functional foods tools for α-glucosidase.

Language: Английский

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Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment

Autophagy, Journal Year: 2023, Volume and Issue: 19(10), P. 2639 - 2656

Published: May 19, 2023

Neuroinflammation caused by microglial activation and consequent neurological impairment are prominent features of diabetes-associated cognitive (DACI). Microglial lipophagy, a significant fraction autophagy contributing to lipid homeostasis inflammation, had mostly been ignored in DACI. droplets (LDs) accumulation is characteristic aging, however, little known about the pathological role lipophagy LDs Therefore, we hypothesized that could be an Achilles's heel exploitable develop effective strategies for DACI therapy. Here, starting with characterization leptin receptor-deficient (db/db) mice high-fat diet STZ (HFD/STZ) induced T2DM mice, as well high-glucose (HG)-treated BV2, human HMC3 primary microglia, revealed HG-dampened was responsible microglia. Mechanistically, accumulated colocalized specific inflammatory amplifier TREM1 (triggering receptor expressed on myeloid cells 1), resulting buildup TREM1, which turn aggravates HG-induced damage subsequently promoted neuroinflammatory cascades via NLRP3 (NLR family pyrin domain containing 3) inflammasome. Moreover, pharmacological blockade LP17 db/db HFD/STZ inhibited reduced hippocampal neuronal damage, consequently improved functions. Taken together, these findings uncover previously unappreciated mechanism impaired lipophagy-induced microglia neuroinflammation DACI, suggesting its translational potential attractive therapeutic target delaying decline.Abbreviations: ACTB: beta actin; AIF1/IBA1: allograft factor 1; ALB: albumin; ARG1: arginase ATG3: related 3; Baf: bafilomycin A1; BECN1: beclin 1, related; BW: body weight; CNS: central nervous system; Co-IP: co-immunoprecipitation; DACI: impairment; DAPI: 4',6-diamidino-2-phenylindole; DGs: dentate gyrus; DLG4/PSD95: discs large MAGUK scaffold protein 4; DMEM: Dulbecco's modified Eagle's medium; DSST: digit symbol substitution test; EDTA: ethylenedinitrilotetraacetic acid; ELISA: enzyme linked immunosorbent assay; GFAP: glial fibrillary acidic protein; HFD: diet; HG: high glucose; IFNG/IFN-γ: interferon gamma; IL1B/IL-1β: interleukin 1 beta; IL4: IL6: 6; IL10: 10; LDs: droplets; LPS: lipopolysaccharide; MAP2: microtubule associated 2; MAP1LC3B/LC3B: light chain 3 MWM: morris water maze; NFKB/NF-κB: nuclear kappa polypeptide gene enhancer B cells; NLRP3: NLR NOS2/iNOS: nitric oxide synthase 2, inducible; NOR: novel object recognition; OA: oleic PA: palmitic PBS: phosphate-buffered saline; PFA: paraformaldehyde; PLIN2: perilipin PLIN3: PS: penicillin-streptomycin solution; RAPA: rapamycin; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) RELA/p65: RELA proto-oncogene, NF-kB subunit; ROS: reactive oxygen species; RT: room temperature; RT-qPCR: Reverse transcription quantitative real-time polymerase reaction; STZ: streptozotocin; SQSTM1/p62: sequestosome SYK: spleen asociated tyrosine kinase; SYP: synaptophysin; T2DM: type 2 diabetes mellitus; TNF/TNF-α: tumor necrosis factor; TREM1: triggering TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling.

Language: Английский

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The global, regional and national burden of type 2 diabetes mellitus in the past, present and future: a systematic analysis of the Global Burden of Disease Study 2019

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

Published: July 14, 2023

To report the global, regional, and national burden of type 2 diabetes mellitus (T2DM) in 2019, assess its trends past, forecast future.The main data source was Global Burden Disease 2019 database. We assessed changes T2DM from 1990 to with joinpoint regression analysis. Age-period-cohort analysis used incidence mortality rate 2020 2034.The has increased generally. The low-middle socio-demographic index (SDI) region had highest increase age-standardized (ASIR), prevalence (ASPR), (ASMR), disability-adjusted life years (ASDR) due T2DM. Nationally, ASIR (r=0.151, p=0.046) decrease ASMR (r=0.355, p<0.001) were positively correlated SDIs. In global ASIR, ASPR, ASMR, ASDR 259.9 (95% UI 240.3-281.4), 5282.9 4853.6-5752.1), 18.5 17.2-19.7), 801.5 55477000-79005200) per 100,000 population, respectively. Additionally, (r=0.153, p=0.030) ASPR (r=0.159, p=0.024) SDIs, while (r=-0.226, p=0.001) (r=-0.171, p=0.015) negatively estimated 284.42, 19.1 2030 2034, population.Globally, past continue increasing. Greater investment prevention is needed.

Language: Английский

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Obesity and its comorbidities, current treatment options and future perspectives: Challenging bariatric surgery?

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 251, P. 108549 - 108549

Published: Oct. 23, 2023

Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure non-alcoholic liver disease are a major health economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy safety. This article provides comprehensive overview of obesity special focus on organ-specific pathomechanisms. Bariatric surgery as the so far most-effective therapeutic strategy, current future strategies will be discussed. An knowledge about gut-brain axis especially identification physiology incretins unfolds high number potential drug candidates impressive weight-reducing potential. Future multi-modal concepts in may surpass effectivity bariatric not regard to weight loss, but also associated comorbidities.

Language: Английский

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Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 6, 2024

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for diabetes. The present study aimed to assess the epidemiological feature of diabetes in patients NAFLD or MAFLD at global levels. Methods Published studies were searched terms that included using PubMed, EMBASE, MEDLINE, Web Science databases from their inception December 2022. pooled regional prevalence incidence density evaluated random-effects meta-analysis. Potential sources heterogeneity investigated stratified meta-analysis meta-regression. Results A total 395 (6,878,568 participants NAFLD; 1,172,637 MAFLD) 40 countries areas among was 28.3% (95% confidence interval 25.2–31.6%) 26.2% (23.9–28.6%) globally. 24.6 per 1000-person year (20.7 29.2) 26.9 (7.3 44.4), respectively. Conclusions describes MAFLD. findings serve as a valuable resource clinical economic impact

Language: Английский

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Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds

Bioactive Materials, Journal Year: 2024, Volume and Issue: 34, P. 366 - 380

Published: Jan. 6, 2024

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, discovery neddylation, a new type post-translational modification, has been found to regulate various crucial biological processes including cell metabolism cycle. Nevertheless, its capacity control healing wounds diabetic remains unknown. This study shows that MLN49224, compound inhibits neddylation at low concentrations, enhances inhibiting polarization M1 macrophages reducing secretion inflammatory factors. Moreover, it concurrently stimulates growth, movement, formation blood vessel endothelial cells, leading expedited individuals diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). membrane shields from being eliminated reticuloendothelial system counteracts proinflammatory cytokines alleviate inflammation surrounding area. extended discharge MLN4924 M-NPs/MLN4924 growth cells tubes, along towards anti-inflammatory M2 phenotype. By loading hydrogel, final formulation able meaningfully wound, suggesting promising engineered nanoplatform tissue engineering.

Language: Английский

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A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders

Cell Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 17, 2025

Abstract According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC exhibit gene expression changes associated disorders, even normal indices. However, the biological mechanisms underlying these remain unclear. The gut microbiota has recently emerged as a promising avenue elucidating TCM principles. Here, we revealed distinct and serum metabolite profiles. A decrease in phytosphingosine was scores disorder severity. Subsequent experiments demonstrated Flavonifractor plautii can biosynthesize phytosphingosine, which also negatively correlated score. Interestingly, both F. levels decreased subjects Fecal transplantation from accelerated development of disorders mice. supplementation ameliorated by increasing gut‒hepatic axis. Mechanistic investigations confirmed directly bind hepatic peroxisome proliferator-activated receptor α (PPARα) activate its nuclear transcription activity, thereby regulating downstream related glucose‒lipid metabolism. Our research indicates product, contributes increases their susceptibility These findings suggest diagnosing may be beneficial identifying at-risk populations among apparently healthy individuals, advancing broader field prevention integration.

Language: Английский

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Anthocyanins in Chronic Diseases: The Power of Purple

Nutrients, Journal Year: 2022, Volume and Issue: 14(10), P. 2161 - 2161

Published: May 23, 2022

Anthocyanins are mainly purple-coloured phenolic compounds of plant origin that as secondary metabolites important in survival. Understanding their health benefits humans requires sourcing these unstable sufficient quantities at a reasonable cost, which has led to improved methods extraction. Dark-coloured fruits, cereals and vegetables current sources compounds. The range potential sustainable is much larger includes non-commercialised native plants from around the world agri-waste containing anthocyanins. In last 5 years, there have been significant advances developing therapeutic anthocyanins chronic human diseases. exert beneficial effects through improvements gut microbiota, oxidative stress inflammation, modulation neuropeptides such insulin-like growth factor-1. Their include reduced cognitive decline; protection organs liver, well cardiovascular system, gastrointestinal tract kidneys; bone obesity; regulation glucose lipid metabolism. This review summarises some mechanisms treatment

Language: Английский

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