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1.
Ernesto Maddaloni Lucia Coraggio Rocco Amendolara Marco G. Baroni Maria G. Cavallo Massimiliano Copetti Efisio Cossu Paola D’Angelo Luca D’Onofrio Salvatore De Cosmo Frida Leonetti Susanna Morano Lelio Morviducci Nicola Napoli Sabrina Prudente Giuseppe Pugliese Kyoungmin Park Rury R. Holman Vincenzo Trischitta Raffaella Buzzetti for the SUMMER Study in Diabetes Group 《Diabetes/metabolism research and reviews》2023,39(5):e3632
Background
Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D).Materials and Methods
Osteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders.Results
Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06–1.72), p = 0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01–1.55), p = 0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02–1.53), p = 0.022), but not osteocalcin.Conclusions
In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease. 相似文献2.
Fahim Ebrahimi Tracey G. Simon Hannes Hagström Jiangwei Sun David Bergman Anders Forss Bjorn Roelstraete Lars Engstrand Jonas F. Ludvigsson 《Liver international》2023,43(10):2186-2197
Background and Aims
Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking.Methods
In this nationwide case–control study, Swedish adults with histologically confirmed early-stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non-cirrhotic fibrosis n = 766) diagnosed January 2007–April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable-adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837).Results
Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35-fold increased odds of NAFLD (95% CI = 1.21–1.51) in a dose-dependent manner (pfor trend < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17–1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08–1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35–1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88–1.30).Conclusions
Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities. 相似文献3.
J. Ukropec Z. Radikova M. Huckova J. Koska A. Kocan E. Sebokova B. Drobna T. Trnovec K. Susienkova V. Labudova D. Gasperikova P. Langer I. Klimes 《Diabetologia》2010,53(5):899-906
Aims/hypothesis
A heavily polluted area of Eastern Slovakia was targeted by the PCBRISK cross-sectional survey to search for possible links between environmental pollution and both prediabetes and diabetes.Methods
Associations of serum levels of five persistent organic pollutants (POPs), namely polychlorinated biphenyls (PCBs), 2,2′-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p′-DDE), 2,2′-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p′-DDT), hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH), with prediabetes and diabetes were investigated in 2,047 adults. Diabetes and prediabetes were diagnosed by fasting plasma glucose in all participants and by OGTT in 1,220 compliant participants.Results
Our population was stratified in terms of individual POPs quintiles and associations between environmental pollution, prediabetes and diabetes were investigated. Prevalence of prediabetes and diabetes increased in a dose-dependent manner, with individuals in upper quintiles of individual POPs showing striking increases in prevalence of prediabetes as shown by OR and 95% CI for PCBs (2.74; 1.92–3.90), DDE (1.86; 1.17–2.95), DDT (2.48; 1.77–3.48), HCB (1.86; 1.7–2.95) and β-HCH (1.97; 1.28–3.04). Interestingly, unlike PCBs, DDT and DDE, increased levels of HCB and β-HCH seemed not to be associated with increased prevalence of diabetes. Nevertheless, individuals in the 5th quintile of the variable expressing the cumulative effect of all five POPs (sum of orders) had a more than tripled prevalence of prediabetes and more than six times higher prevalence of diabetes when compared with the 1st referent quintile.Conclusions/interpretation
Increasing serum concentrations of individual POPs considerably increased prevalence of prediabetes and diabetes in a dose-dependent manner. Interaction of industrial and agricultural pollutants in increasing prevalence of prediabetes or diabetes is likely. 相似文献4.
Pinar Yilmaz Louise J. M. Alferink Lotte G. M. Cremers Sarwa D. Murad Wiro J. Niessen M. Arfan Ikram Meike W. Vernooij 《Liver international》2023,43(6):1256-1268
Background & Aims
Impaired liver function affects brain health and therefore understanding potential mechanisms for subclinical liver disease is essential. We assessed the liver–brain associations using liver measures with brain imaging markers, and cognitive measures in the general population.Methods
Within the population-based Rotterdam Study, liver serum and imaging measures (ultrasound and transient elastography), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) and fibrosis phenotypes, and brain structure were determined in 3493 non-demented and stroke-free participants in 2009–2014. This resulted in subgroups of n = 3493 for MAFLD (mean age 69 ± 9 years, 56% ♀), n = 2938 for NAFLD (mean age 70 ± 9 years, 56% ♀) and n = 2252 for fibrosis (mean age 65 ± 7 years, 54% ♀). Imaging markers of small vessel disease and neurodegeneration, cerebral blood flow (CBF) and brain perfusion (BP) were acquired from brain MRI (1.5-tesla). General cognitive function was assessed by Mini-Mental State Examination and the g-factor. Multiple linear and logistic regression models were used for liver-brain associations and adjusted for age, sex, intracranial volume, cardiovascular risk factors and alcohol use.Results
Higher gamma-glutamyltransferase (GGT) levels were significantly associated with smaller total brain volume (TBV, standardized mean difference (SMD), −0.02, 95% confidence interval (CI) (−0.03 to −0.01); p = 8.4·10−4), grey matter volumes, and lower CBF and BP. Liver serum measures were not related to small vessel disease markers, nor to white matter microstructural integrity or general cognition. Participants with ultrasound-based liver steatosis had a higher fractional anisotropy (FA, SMD 0.11, 95% CI (0.04 to 0.17), p = 1.5·10−3) and lower CBF and BP. MAFLD and NAFLD phenotypes were associated with alterations in white matter microstructural integrity (NAFLD ~ FA, SMD 0.14, 95% CI (0.07 to 0.22), p = 1.6·10−4; NAFLD ~ mean diffusivity, SMD −0.12, 95% CI (−0.18 to −0.05), p = 4.7·10−4) and also with lower CBF and BP (MAFLD ~ CBF, SMD −0.13, 95% CI (−0.20 to −0.06), p = 3.1·10−4; MAFLD ~ BP, SMD −0.12, 95% CI (−0.20 to −0.05), p = 1.6·10−3). Furthermore, fibrosis phenotypes were related to TBV, grey and white matter volumes.Conclusions
Presence of liver steatosis, fibrosis and elevated serum GGT are associated with structural and hemodynamic brain markers in a population-based cross-sectional setting. Understanding the hepatic role in brain changes can target modifiable factors and prevent brain dysfunction. 相似文献5.
Roberta I. Jordan Yousuf ElMokhallalati Lynsey Corless Michael Bennett 《Liver international》2023,43(2):308-316
Background and Aims
Patients with liver disease struggle to access palliative care. We aimed to compare carers' perceptions of end-of-life care for decedents with non-malignant liver disease, malignant liver disease and other non-malignant diseases, and to identify associated factors in non-malignant liver disease.Methods
A retrospective analysis of individual-level data from the National Survey of Bereaved People 2011–2015.Results
More decedents with non-malignant liver disease died in hospital than other diseases (76.9% vs. 40.9% vs. 50.2%, p < .001), despite 89% wishing to die at home. Fewer decedents received home/hospice specialist palliative care compared with those with malignant liver disease (10.0% vs. 54.6%, p < .001). Carers of decedents with non-malignant liver disease were less likely to rate overall end-of-life care quality as outstanding/excellent (29.3% vs. 43.9% vs. 42.3%, p < .001). For this group, poorer care was associated with younger (65–74 vs. 18–64 years, OR [odds ratio] 1.39, p = .01), more socially deprived decedents (OR .78, p = .02), and better care with greater social support (OR 1.82, p < .001) and community specialist palliative care involvement (OR 1.80, p < .001). There was no association between outstanding/excellent rating and underlying cause of non-malignant liver disease (alcohol-related vs. non-alcohol-related, p = .92) or place of death (hospital vs. non-hospital, p = .476).Conclusions
End-of-life care could be improved by integrating hepatology and community services, particularly specialist palliative care, and advance care planning to facilitate care and death (where desired) at home. However, death in hospital may be appropriate for those with non-malignant liver disease. 相似文献6.
Eline H. van den Berg Jose L. Flores-Guerrero Erwin Garcia Margery A. Connelly Vincent E. de Meijer TransplantLines Investigators Stephan J. L. Bakker Hans Blokzijl Robin P. F. Dullaart 《Liver international》2023,43(2):424-433
Background and Aims
The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity.Methods
Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score.Results
Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively).Conclusion
Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation. 相似文献7.
Matthias Egger Angela Horvath Florian Prüller Peter Fickert Malcolm Finkelman Lisa Kriegl Henning Grønbæk Holger Jon Møller Juergen Prattes Robert Krause Martin Hoenigl Vanessa Stadlbauer 《Liver international》2023,43(9):1975-1983
Background & Aims
On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host–pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.Methods
Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.Results
Patients with cirrhosis Child–Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2–25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8–26.3).Discussion
We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host–pathogen interactions and potentially introduce points of application for therapeutic interventions. 相似文献8.
Jessie L. Werner Lisa Christopher‐Stine Sharon R. Ghazarian Katherine S. Pak Jordan E. Kus Natalie R. Daya Thomas E. Lloyd Andrew L. Mammen 《Arthritis \u0026amp; Rheumatology》2012,64(12):4087-4093
Objective
Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are found in patients with statin‐associated immune‐mediated necrotizing myopathy and, less commonly, in statin‐unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti‐HMGCR antibody levels with disease activity.Methods
Anti‐HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti‐HMGCR–positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin‐exposed and 5 statin‐unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.Results
Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin‐exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin‐exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti‐HMGCR antibody levels did not normalize in any patient.Conclusion
In the entire cohort, initial anti‐HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin‐exposed patients had significant improvements in CK levels and strength whereas statin‐unexposed patients did not, suggesting a phenotypic difference between statin‐exposed and statin‐unexposed anti‐HMGCR–positive patients.9.
Ian J. Neeland Shruti Singh Darren K. McGuire Gloria L. Vega Thomas Roddy Dermot F. Reilly Jose Castro-Perez Julia Kozlitina Philipp E. Scherer 《Diabetologia》2018,61(12):2570-2579
Aims/hypothesis
Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort.Methods
A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed.Results
The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p?<?0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β?=?0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β?=??0.14 to ?0.16, p?<?0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β?=?0.08 to 0.09, p?<?0.001) and inversely with polyunsaturated ceramides (β?=??0.06 to ?0.07, p?<?0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors.Conclusions/interpretation
Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.10.
Michael Casten Simone Herbert David J. Smith Kathy Petoumenos Craig Coorey Natalie Edmiston 《HIV medicine》2023,24(7):807-817
Introduction
Multimorbidity is common among people living with HIV (PLWH), with numerous cross-sectional studies demonstrating associations with older age and past immunosuppression. Little is known about the progression of multimorbidity, particularly in the setting of long-term access to antiretrovirals. This study aims to determine factors predictive of change in multimorbidity in PLWH.Methods
People living with HIV who attended a regional HIV service were recruited to a consented observational cohort between September 2016 and March 2020. Demographic data, laboratory results and a Cumulative Illness Rating Scale (CIRS) were collected at enrolment and first clinical review of every subsequent year. Change in CIRS score was calculated from enrolment to February 2021. Associations with change were determined through univariate and multivariate linear regression.Results
Of 253 people, median age was 58.9 [interquartile range (IQR): 51.9–64.4] years, 91.3% were male, and HIV was diagnosed a median of 22.16 years (IQR: 12.1–30.9) beforehand. Length of time in the study was a median of 134 weeks (IQR: 89.0–179.0), in which a mean CIRS score change of 1.21 (SD 2.60) was observed. Being older (p < 0.001) and having a higher body mass index (p = 0.008) and diabetes (p = 0.014) were associated with an increased likelihood of worsening multimorbidity. PLWH with a higher level of multimorbidity at baseline were less likely to worsen over time (p < 0.001).Conclusion
As diabetes and weight predict worsening multimorbidity, routine diabetes screening, body mass index measurement, and multimorbidity status awareness are recommended. 相似文献11.
Alessandro Mantovani Alessandro Csermely Annalisa Castagna Elisa Antinori Elisa Danese Chiara Zusi Elena Sani Federico Ravaioli Antonio Colecchia Claudio Maffeis Luca Valenti Domenico Girelli Giovanni Targher 《Liver international》2023,43(11):2434-2444
Background
Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).Methods
We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively.Results
After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3–4.0) kPa, 2nd tertile: 5.3 (4.9–5.9) kPa and 3rd tertile: 7.9 (6.7–9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1–147) vs. 85.8 (48.3–139) vs. 111 (59.3–203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1–5.2) vs. 4.4 (2.5–7.3) vs. 4.1 (1.9–6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23–3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15–3.13, p = 0.013).Conclusions
Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders. 相似文献12.
Wiktor Smyk Ifigeneia Papapostoli Michał Żorniak Panagiotis Sklavounos Łukasz Blukacz Paweł Madej Andreani Koutsou Susanne N. Weber Bettina Friesenhahn-Ochs Maciej Cebula Joanna Bosowska Erich-Franz Solomayer Marek Hartleb Piotr Milkiewicz Frank Lammert Caroline S. Stokes Marcin Krawczyk 《Liver international》2023,43(5):1080-1088
Background & Aims
Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS.Methods
Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis.Results
A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05).Conclusions
FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS. 相似文献13.
Serena Pelusi Cristiana Bianco Massimo Colombo Giuliana Cologni Paolo del Poggio Nicola Pugliese Daniele Prati Marie Graciella Pigozzi Roberta D'Ambrosio Pietro Lampertico Stefano Fagiuoli Luca Valenti for the NAVIGATORE-Lombardia Network 《Liver international》2023,43(7):1593-1603
Background and Aims
Metabolic dysfunction (MD)-associated fatty liver disease has been proposed to identify individuals at risk of liver events irrespectively of the contemporary presence of other liver diseases. The aim of this study was to examine the impact of MD in patients cured of chronic hepatis C (CHC).Patients and Methods
We analysed data from a real-life cohort of 2611 Italian patients cured of CHC with direct antiviral agents and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history (age 61.4 ± 11.8 years, 63.9% males, median follow-up 34, 24–40 months). Information about ultrasonographic steatosis (US) after sustained virological response was available in 1978.Results
MD affected 58% of patients, diagnosed due to the presence of diabetes (MD-diabetes, 19%), overweight without diabetes (MD-overweight, 37%) or multiple metabolic abnormalities without overweight and diabetes (MD-metabolic, 2%). MD was more frequent than and not coincident with US (32% MD-only, 23% MD-US and 13% US-only). MD was associated with higher liver stiffness (p < 0.05), particularly in patients with MD-diabetes and MD-only subgroups, comprising older individuals with more advanced metabolic and liver disease (p < 0.05). At Cox proportional hazard multivariable analysis, MD was associated with increased risk of HCC (HR 1.97, 95% CI 1.27–3.04; p = 0.0023). Further classification according to diagnostic criteria improved risk stratification (p < 0.0001), with the highest risk observed in patients with MD-diabetes. Patients with MD-only appeared at highest risk since the sustained virological response achievement (p = 0.008), with a later catch-up of those with combined MD-US, whereas US-only was not associated with HCC.Conclusions
MD is more prevalent than US in patients cured of CHC with advanced fibrosis and identifies more accurately individuals at risk of developing HCC. 相似文献14.
S. Dusanov J. Ruzzin H. Kiviranta T.O. Klemsdal L. Retterstøl P. Rantakokko R. Airaksinen S. Djurovic S. Tonstad 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2018,28(7):735-742
Background and aims
Persons with “metabolically healthy” obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs.Methods and results
A cross-sectional study among 161 men and 270 women with BMI >35 kg/m2 and comorbidity, or >40 kg/m2. Circulating concentrations of 15 POPs were stratified by number of metabolic syndrome components. In multiple logistic regression analysis odds ratios between top quartile POPs and metabolic risk factors versus POPs below the top quartile were calculated adjusting for age, gender, body mass index, smoking status, alcohol consumption and cholesterol concentrations. Age-adjusted concentrations of trans-nonachlor and dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) increased with number of metabolic syndrome components in both genders (p < 0.001), while the organochlorine pesticides HCB, β-HCH and p,p’DDE increased only in women (p < 0.008). Organochlorine pesticides in the top quartile were associated with metabolic syndrome as were dioxin-like and non-dioxin-like PCBs (OR 2.3 [95% CI 1.3–4.0]; OR 2.5 [95% CI 1.3–4.8] and 2.0 [95% CI 1.1–3.8], respectively). Organochlorine pesticides were associated with HDL cholesterol and glucose (OR = 2.0 [95% CI = 1.1–3.4]; 2.4 [95% CI = 1.4–4.0], respectively). Dioxin-like PCBs were associated with diastolic blood pressure, glucose and homeostatic model assessment-insulin resistance index (OR = 2.0 [95% CI = 1.1–3.6], 2.1 [95% CI = 1.2–3.6] and 2.1 [95% CI = 1.0–4.3], respectively).Conclusion
In subjects with morbid obesity, metabolic syndrome was related to circulating levels of organochlorine pesticides and PCBs suggesting that these compounds aggravate clinically relevant complications of obesity. 相似文献15.
Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study
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Michael A. Rosenberg Molly M. Shores Alvin M. Matsumoto Petra Bůžková Leslie A. Lange Richard A. Kronmal Susan R. Heckbert Kenneth J. Mukamal 《Clinical cardiology》2018,41(6):830-836
Background
Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.Hypothesis
Low serum androgens are associated with an increased risk of AF.Methods
We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone–binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.Results
After median follow‐up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT‐proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01–2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint‐specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9–65.3 nmol/L) had increased risk.Conclusions
Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association. 相似文献16.
Tariq O. Faquih Jan Bert van Klinken Ruifang Li-Gao Raymond Noordam Diana van Heemst Sebastiaan Boone Patricia A. Sheridan Gregory Michelotti Hildo Lamb Renée de Mutsert Frits R. Rosendaal Astrid van Hylckama Vlieg Ko Willems van Dijk Dennis O. Mook-Kanamori 《Liver international》2023,43(7):1458-1472
Background and Aims
Non-alcoholic fatty liver disease (NAFLD) is characterized by the pathological accumulation of triglycerides in hepatocytes and is associated with insulin resistance, atherogenic dyslipidaemia and cardiometabolic diseases. Thus far, the extent of metabolic dysregulation associated with hepatic triglyceride accumulation has not been fully addressed. In this study, we aimed to identify metabolites associated with hepatic triglyceride content (HTGC) and map these associations using network analysis.Methods
To gain insight in the spectrum of metabolites associated with hepatic triglyceride accumulation, we performed a comprehensive plasma metabolomics screening of 1363 metabolites in apparently healthy middle aged (age 45–65) individuals (N = 496) in whom HTGC was measured by proton magnetic resonance spectroscopy. An atlas of metabolite–HTGC associations, based on univariate results, was created using correlation-based Gaussian graphical model (GGM) and genome scale metabolic model network analyses. Pathways associated with the clinical prognosis marker fibrosis 4 (FIB-4) index were tested using a closed global test.Results
Our analyses revealed that 118 metabolites were univariately associated with HTGC (p-value <6.59 × 10−5), including 106 endogenous, 1 xenobiotic and 11 partially characterized/uncharacterized metabolites. These associations were mapped to several biological pathways including branched amino acids (BCAA), diglycerols, sphingomyelin, glucosyl-ceramide and lactosyl-ceramide. We also identified a novel possible HTGC-related pathway connecting glutamate, metabolonic lactone sulphate and X-15245 using the GGM network. These pathways were confirmed to be associated with the FIB-4 index as well. The full interactive metabolite-HTGC atlas is provided online: https://tofaquih.github.io/AtlasLiver/ .Conclusions
The combined network and pathway analyses indicated extensive associations between BCAA and the lipids pathways with HTGC and the FIB-4 index. Moreover, we report a novel pathway glutamate-metabolonic lactone sulphate-X-15245 with a potential strong association with HTGC. These findings can aid elucidating HTGC metabolomic profiles and provide insight into novel drug targets for fibrosis-related outcomes. 相似文献17.
Karin Dilger Jörg Metzler Johann Christian Bode Ulrich Klotz 《Journal of hepatology》1997,27(6):1009-1014
Background/Aims: In addition to the possible toxicological impact of cytochrome P4502E1 (CYP2E1) in alcohol-induced liver damage, its activity can be regarded as a variable for dug action in patients with alcoholic liver disease as CYP2E1 is involved in the metabolism of several drugs, for example, paracetamol and halogenated anesthetics. The purpose of our study was to acquire detailed knowledge of CYP2E1 activity in patients with progressingly severe manifestations of alcoholic liver disease.Methods: The concentration ratio of 6-hydroxy-chlorzoxazone/chlorzoxazone in plasma 2 h after ingestion of 500 mg chlorzoxazone (so-called metabolic ratio) has been shown to reflect CYP2E1 activity in vivo. We examined CYP2E1 activity in 56 Caucasian inpatients with minor (n=20), more pronounced (n=14) and severe alcoholic liver disease (n=22). Alcohol abusers were compared to healthy teetotallers (n=14).Results: Metabolic ratios were increased 3-fold in actively drinking (ethanol-induced) compared to abstaining (non-induced) patients with alcoholic liver disease (1.19±0.84 vs. 0.44±0.45, mean±SD, (p<0.0001). CYP2E1 activity was significantly lower in non-induced patients with severe alcoholic liver disease (0.19±0.10) than in healthy controls (0.50±0.28, p<0.01), abstaning alcohol abusers with minor (0.67±0.60, p<0.01) and more pronounced alcoholic liver disease (0.53±0.31, p<0.01). When non-induced patients with alcoholic liver disease were arranged in progressing order of liver damage (minor, more pronounced, severe alcoholic liver disease), there was a significant decline in CYP2E1 activity (p=0.0008).Conclusions: In non-induced patients, CYP2E1 activity decreases in line with severity of alcoholic liver disease. CYP2E1-mediated drug metabolism is significantly impaired in severe alcoholic liver disease. 相似文献
18.
Bing Yu Yan Zheng Jennifer A. Nettleton Danny Alexander Josef Coresh Eric Boerwinkle 《Clinical journal of the American Society of Nephrology》2014,9(8):1410-1417
Background and objectives
Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.Design, setting, participants, & measurements
In total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD.Results
Forty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m2 per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (−14.2 ml/min per 1.73 m2 per +1 SD; 95% confidence interval, −17.0 to −11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted.Conclusions
These data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification. 相似文献19.
Kai Tonda MD Yu Iwabuchi MD Tohru Shiga MD Yoshiki Owaki RT Arashi Fujita RT Takehiro Nakahara MD Ryosuke Sakurai MD Atsushi Shimizu MD Yoshitake Yamada MD Masahiro Okada MD Masahiro Jinzaki MD 《Diabetes, obesity & metabolism》2023,25(12):3521-3528
Aims
To assess the impact of various patient characteristics on the dynamics of liver glucose metabolism using automated multiparametric imaging with whole-body dynamic 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET).Materials and Methods
We retrospectively enrolled 540 patients who underwent whole-body dynamic FDG-PET. Three quantitative indices representing hepatic glucose metabolism [mean standardized uptake value normalized by lean body mass (SULmean), metabolic glucose rate (kinetic index) and distribution volume (DV)] were measured from multiparametric PET images produced automatically based on the Patlak plot model. Patient characteristics including age, sex, body mass index, fasting time, blood glucose level, and the presence of diabetes mellitus (DM) or hepatic steatosis (HS) were collected. We examined the correlations between the characteristic factors and three quantitative indices using multiple regression analysis.Results
The success rate of kinetic analysis using multiparametric PET imaging was 93.3% (504/540). Hepatic SULmean was significantly correlated with age (p < .001), sex (p < .001) and blood glucose level (p = .002). DV was significantly correlated with age (p = .033), sex (p < .001), body mass index (p = .002), fasting time (p = .043) and the presence of HS (p = .002). The kinetic index was significantly correlated with age (p < .001) and sex (p = .004). In the comparison of the healthy, DM and HS groups, patients with DM had a significantly increased SULmean, whereas patients with HS had a significantly decreased DV.Conclusions
Our results showed that liver glucose metabolism was influenced by various patient characteristic factors. Multiparametric FDG-PET imaging can be used to analyse the kinetics of liver glucose metabolism in routine clinical practice. 相似文献20.
Jason P. Linefsky Kevin D. O'Brien Michael Sachs Ronit Katz John Eng Erin D. Michos Matthew J. Budoff Ian de Boer Bryan Kestenbaum 《Atherosclerosis》2014