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  • 1
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 11 ( 2020-06-02)
    Kurzfassung: FGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF 21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF 21 could predict incident atherosclerotic cardiovascular disease in a 7‐year prospective cohort. Methods and Results Baseline serum FGF 21 was measured in a cross‐sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population‐based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross‐sectional study, FGF 21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis ( P 〈 0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow‐up. Baseline FGF 21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF 21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all P 〈 0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors. Conclusions This study provides the first evidence that FGF 21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF 21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.
    Materialart: Online-Ressource
    ISSN: 2047-9980
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2020
    ZDB Id: 2653953-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Diabetes and Vascular Disease Research, SAGE Publications, Vol. 18, No. 4 ( 2021-07), p. 147916412110325-
    Kurzfassung: Neutrophil elastase (NE) and proteinase 3 (PR3) are novel inflammation biomarkers. We investigated their associations with chronic complications, determinants of biomarker levels and effects of fenofibrate in patients with type 2 diabetes mellitus (T2DM) from Fenofibrate Intervention and Event Lowering in Diabetes study. Methods: Plasma NE and PR3 levels were quantified at baseline ( n = 2000), and relationships with complications over 5-years assessed. Effects of fenofibrate on biomarker levels ( n = 200) were determined at four follow-up visits. Results: Higher waist-to-hip ratio, homocysteine and C-reactive protein and lower apoA-II were determinants of higher NE and PR3 levels. Higher NE levels were associated with on-trial stroke and cardiovascular mortality, and higher PR3 levels with on-trial stroke, but associations were not significant after adjustment for confounding factors. Although higher NE and PR3 levels were associated with baseline total microvascular disease, only NE levels were associated with on-trial neuropathy or amputation. These associations were not significant after adjusting for multiple comparisons. NE and PR3 levels did not change with fenofibrate. Conclusions: In T2DM plasma NE and PR3 levels are associated with vascular risk factors, and total microvascular disease at baseline, but on rigorous analyses were not associated with on-trial complications. Levels were not changed by fenofibrate.
    Materialart: Online-Ressource
    ISSN: 1479-1641 , 1752-8984
    Sprache: Englisch
    Verlag: SAGE Publications
    Publikationsdatum: 2021
    ZDB Id: 2250797-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Springer Science and Business Media LLC ; 2018
    In:  Nature Communications Vol. 9, No. 1 ( 2018-01-18)
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-01-18)
    Kurzfassung: Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are well-documented, uncertainty about its role in regulating excessive energy intake remains. Here, we show that FGF21 improves systemic insulin sensitivity by promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21 levels positively correlate with the SAT area in insulin-sensitive obese individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to a level equivalent to that in obesity restores SAT mass and reverses insulin resistance in FGF21KO, but not in adipose-specific βklotho knockout mice. Moreover, transplantation of SAT from wild-type to FGF21KO mice improves insulin sensitivity in the recipients. Mechanistically, circulating FGF21 upregulates adiponectin in SAT, accompanied by an increase of M2 macrophage polarization. We propose that elevated levels of endogenous FGF21 in obesity serve as a defense mechanism to protect against systemic insulin resistance.
    Materialart: Online-Ressource
    ISSN: 2041-1723
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2018
    ZDB Id: 2553671-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Cell Reports Medicine, Elsevier BV, ( 2023-10), p. 101213-
    Materialart: Online-Ressource
    ISSN: 2666-3791
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2023
    ZDB Id: 3019420-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Advanced Science, Wiley, Vol. 7, No. 22 ( 2020-11)
    Kurzfassung: Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform‐based metabolomics study is performed. In this study, a total of 905 subjects with diabetes without DR (NDR) and with DR at different clinical stages are recruited. Multiplatform metabolomics methods are used to characterize the serum metabolic profiles and to screen and validate the DR biomarkers. Based on the criteria p 〈  0.05 and false‐discovery rate 〈  0.05, 348 and 290 metabolites are significantly associated with the pathogenesis of DR and early‐stage DR, respectively. The biomarker panel consisting of 12‐hydroxyeicosatetraenoic acid (12‐HETE) and 2‐piperidone exhibited better diagnostic performance than hemoglobin A1c (HbA1c) in differentiating DR from diabetes, with AUCs of 0.946 versus 0.691 and 0.928 versus 0.648 in the discovery and validation sets, respectively. In addition, this panel showed higher sensitivity in early‐stage DR detection than HbA1c. In conclusion, this multiplatform‐based metabolomics study comprehensively revealed the metabolic dysregulation associated with DR onset and progression. The defined biomarker panel can be used for detection of DR and early‐stage DR.
    Materialart: Online-Ressource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2020
    ZDB Id: 2808093-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-11-28)
    Kurzfassung: Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls. FGF21 levels were significantly increased in AHB patients and rapidly returned to normal levels after treatment. FGF21 levels reflected the degree of liver injury caused by AHB. However, serum FGF21 levels were decreased in CHB patients especially in those who developed cirrhosis and were associated with hepatic protein synthesis capacity. Serum FGF21 in CHB patients were increased with the occurrence of ACLF. Notably, in CHB patients who developed HCC, serum FGF21 exhibited a dramatic increase, which may provide important information on monitoring tumorigenesis in CHB patients. In conclusion, we revealed the diverse changes of circulating FGF21 in HBV-related diseases. FGF21 may be a useful biomarker in monitoring the tumorigenesis in patients with CHB.
    Materialart: Online-Ressource
    ISSN: 2045-2322
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2017
    ZDB Id: 2615211-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-11)
    Kurzfassung: Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30 and total cell death marker CK18 M65ED in monitoring the different stages of NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese subjects. Predictive performances for monitoring the different stages of NAFLD were assessed by logistic regression and receiver-operating characteristic (ROC) curves. We found baseline FGF21 but not CK18 level was an independent predictor for the development of simple steatosis. NAFLD patients who had remission during follow-up had significantly lower baseline M30 levels than those who sustained NAFLD (84.74U/L [53.26–135.79] vs . 118.47U/L [87.16–188.89], P = 0.012). M65ED was independently predictive of progressing to suspected non-alcoholic steatohepatitis (NASH) in NAFLD patients. These results suggest that FGF21 can be used for early identification of hepatic steatosis. On the other hand, CK18 including M30 and M65ED, are predictive of the prognosis of NAFLD patients. FGF21 and CK18 might play differential roles and have complementary value in non-invasive identification and monitoring the outcome of NAFLD patients.
    Materialart: Online-Ressource
    ISSN: 2045-2322
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2017
    ZDB Id: 2615211-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
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    Springer Science and Business Media LLC ; 2021
    In:  Cardiovascular Diabetology Vol. 20, No. 1 ( 2021-12)
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2021-12)
    Kurzfassung: The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study. Methods We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis. Results At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes ( p for trend  〈  0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p  = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p  = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p   〉  0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone. Conclusions FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia.
    Materialart: Online-Ressource
    ISSN: 1475-2840
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2093769-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-05-28)
    Kurzfassung: Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading.
    Materialart: Online-Ressource
    ISSN: 2041-1723
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2553671-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-7-12)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-7-12)
    Kurzfassung: Type 2 diabetes patients have abdominal obesity and low thigh circumference. Previous studies have mainly focused on the role of exercise in reducing body weight and fat mass, improving glucose and lipid metabolism, with a lack of evaluation on the loss of muscle mass, diabetes complications, energy metabolism, and brain health. Moreover, whether the potential physiological benefit of exercise for diabetes mellitus is related to the modulation of the microbiota-gut-brain axis remains unclear. Multi-omics approaches and multidimensional evaluations may help systematically and comprehensively correlate physical exercise and the metabolic benefits. Methods and Analysis This study is a randomized controlled clinical trial. A total of 100 sedentary patients with type 2 diabetes will be allocated to either an exercise or a control group in a 1:1 ratio. Participants in the exercise group will receive a 16-week combined aerobic and resistance exercise training, while those in the control group will maintain their sedentary lifestyle unchanged. Additionally, all participants will receive a diet administration to control the confounding effects of diet. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include body fat mass change rate (%), and changes in anthropometric indicators (body weight, waist, hip, and thigh circumference), clinical biochemical indicators (glycated hemoglobin, blood glucose, insulin sensitivity, blood lipid, liver enzyme, and renal function), brain health (appetite, mood, and cognitive function), immunologic function, metagenomics, metabolomics, energy expenditure, cardiopulmonary fitness, exercise-related indicators, fatty liver, cytokines (fibroblast growth factor 21, fibroblast growth factor 19, adiponectin, fatty acid-binding protein 4, and lipocalin 2), vascular endothelial function, autonomic nervous function, and glucose fluctuation. Discussion This study will evaluate the effect of a 16-week combined aerobic and resistance exercise regimen on patients with diabetes. The results will provide a comprehensive evaluation of the physiological effects of exercise, and reveal the role of the microbiota-gut-brain axis in exercise-induced metabolic benefits to diabetes. Clinical Trial Registration http://www.chictr.org.cn/searchproj.aspx , identifier ChiCTR2100046148.
    Materialart: Online-Ressource
    ISSN: 1664-2392
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2592084-4
    Standort Signatur Einschränkungen Verfügbarkeit
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