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Serum Ferritin and the Risk of Metabolic Syndrome: A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies.
Zhang, WCB, Xing, Y, Shao, B
Biomedical and environmental sciences : BES. 2021;(8):623-631
Abstract
OBJECTIVE This study aims to assess the dose-response relationship between serum ferritin (SF) and metabolic syndrome (MetS) in the two sexes. METHODS We searched for articles on PubMed, the Cochrane Library, EMBASE, and the Web of Science databases that were published from 1950 to 2020. The summary odds ratio ( OR) and 95% confidence interval ( CI) of the association between SF and MetS were estimated using a random-effects model through a meta-analysis. Based on the methods described by Greenland and Longnecker, we explored the dose-response relationship between the two sexes. RESULTS This study included 14 studies and 74,710 samples. The results of the classical meta-analysis showed that SF was positively associated with MetS ( OR = 1.77, 95% CI: 1.59-1.98). Regarding the components of MetS (8 studies included), the results showed that SF was positively associated with abdominal obesity ( OR = 1.42, 95% CI: 1.24-1.62), elevated fasting plasma glucose ( OR = 1.84, 95% CI: 1.50-2.25), elevated blood pressure ( OR = 1.17, 95% CI: 1.08-1.26), elevated triglycerides ( OR= 2.09, 95% CI: 1.72-2.54), and reduced high-density lipoprotein cholesterol ( OR = 1.33, 95% CI: 1.19-1.49). In the linear dose-response meta-analysis, the ORs of males, females, and postmenopausal females were 1.14 (95% CI: 1.13-1.16), 1.32 (95% CI: 1.26-1.39), and 1.34 (95% CI: 1.22-1.47), respectively. CONCLUSIONS Our study shows that SF is significantly and positively associated with MetS, and the risk in the male population is higher than that in the female population. This finding also supports the recommendation of using SF as an early warning marker of MetS.
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Decreased serum ferritin may be associated with increased restless legs syndrome in Parkinson's disease (PD): a meta-analysis for the diagnosis of RLS in PD patients.
Li, K, Liu, B, Wang, F, Bao, J, Wu, C, Huang, X, Hu, F, Xu, Z, Ren, H, Yang, X
The International journal of neuroscience. 2019;(10):995-1003
Abstract
Objective: Restless legs syndrome (RLS) is one of the most common non-motor symptoms of Parkinson's disease (PD), but its pathogenesis in a PD background is unclear. Abnormal iron metabolism may be involved, in which case it may be a marker of RLS risk. Here, the literature was systematically searched and meta-analyzed to compare iron metabolism markers between PD patients with or without RLS. Method: The databases PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, Web of Science, and SinoMed were searched for case-control and observational studies examining RLS-related changes in iron metabolism in PD, in terms of serum iron, serum ferritin and hemoglobin. Eligible studies were meta-analyzed using Stata 12.0. Results: Meta-analysis of 11 case-control studies showed that serum ferritin concentration was lower in PD patients with RLS than in those without RLS. (95%CI -0.32 to -0.03, p = 0.018). In contrast, levels of serum iron or hemoglobin did not differ significantly between PD patients with or without RLS. Conclusion: This meta-analysis may provide the first reliable pooled estimate of the correlation between abnormal iron metabolism and RLS in PD. The available evidence indicates that levels of ferritin, but not of serum iron or hemoglobin, correlate significantly with RLS in PD, with lower ferritin levels correlating to greater prevalence of RLS.
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Iron overload in congenital haemolytic anaemias: role of hepcidin and cytokines and predictive value of ferritin and transferrin saturation.
Barcellini, W, Zaninoni, A, Gregorini, AI, Soverini, G, Duca, L, Fattizzo, B, Giannotta, JA, Pedrotti, P, Vercellati, C, Marcello, AP, et al
British journal of haematology. 2019;(3):523-531
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Abstract
Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non-transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis-associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ-interferon (IFN-γ) was increased, and both interleukin 6 and IFN-γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs.
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Ferritin, metabolic syndrome and its components: A systematic review and meta-analysis.
Suárez-Ortegón, MF, Ensaldo-Carrasco, E, Shi, T, McLachlan, S, Fernández-Real, JM, Wild, SH
Atherosclerosis. 2018;:97-106
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BACKGROUND AND AIMS Mechanisms for the association between iron stores and risk factors for diabetes and cardiovascular disease, such as metabolic syndrome (MetS) and its components, are still not clear. We evaluated the associations between ferritin levels, MetS and its individual components, and potential role of confounding, in a meta-analysis. METHODS We searched articles in MEDLINE and EMBASE until February 14th, 2018. There were two approaches: meta-analysis of 1) cross-sectional and longitudinal studies and 2) only cross-sectional studies. Meta-regressions were conducted to identify sources of heterogeneity in the associations of ferritin with MetS and its individual components. RESULTS Information from 26 studies (5 prospective) was systematically reviewed and 21 studies were meta-analysed. The pooled OR for MetS by increased ferritin was 1.78 (95%CI: 1.60-1.97) in the meta-analysis 1, and 1.70 (95%CI: 1.49-1.95) in the meta-analysis 2. The pooled association was weaker in studies adjusted for hepatic injury markers (meta-regression coefficient (95% CI): -0.34 (-0.60,-0.09) p = 0.008) and body mass index (BMI) (meta-regression coefficient (95% CI): -0.27 (-0.53,-0.01) p = 0.039). Among MetS components, the pooled association with increased ferritin was strongest with high triglycerides [OR (95%CI): 1.96 (1.65-2.32)] and high glucose levels [OR 95%CI: 1.60 (1.40-1.82)]. Higher cut-off points used to define high ferritin concentrations were more strongly associated with high triglycerides [meta-regression coefficient (95% CI): 0.22 (0.03, 0.041), p = 0.023]. CONCLUSIONS High triglycerides and glucose are the components more strongly associated with ferritin. Hepatic injury and BMI appear to influence the ferritin-MetS association, and a threshold effect of high ferritin concentration on the ferritin-high triglycerides association was observed.
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Investigation and management of a raised serum ferritin.
Cullis, JO, Fitzsimons, EJ, Griffiths, WJ, Tsochatzis, E, Thomas, DW, ,
British journal of haematology. 2018;(3):331-340
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Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.
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Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients.
Lainé, F, Ruivard, M, Loustaud-Ratti, V, Bonnet, F, Calès, P, Bardou-Jacquet, E, Sacher-Huvelin, S, Causse, X, Beusnel, C, Renault, A, et al
Hepatology (Baltimore, Md.). 2017;(2):465-474
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UNLABELLED Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild increase of iron stores in insulin-resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron >50 μmol/g at magnetic resonance imaging to compare the metabolic and hepatic outcomes of 1-year maintenance of serum ferritin levels <50 μg/L by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only. Patients were randomly assigned (1:1) with stratification by center (n = 8) and hyperglycemia (>5.6 mmol/L). Sample size was calculated to provide 90% power and a difference in fasting glycemia of 0.25 mmol/L. Analysis was done in an intention-to-treat population. In 2010-2014, 146 patients were randomly assigned to receive venesections with LFDA and 128 to LFDA only. At the end of the study, comparison of iron-depleted patients and controls showed ferritin levels 71 ± 48 μg/L after removal of 4.9 ± 1.6 L of blood versus 733 ± 277 μg/L (P < 0.0001), glycemia 5.44 ± 0.7 versus 5.49 ± 0.7 mmol/L (P = 0.57), body weight +0.5 ± 4.3% versus -0.6 ± 3.3% (P = 0.03), homeostasis model of assessment of insulin resistance 3.39 versus 2.40 (P = 0.002), alanine aminotransaminase 33 ± 22 versus 37 ± 21 IU/L (P = 0.10), aspartate aminotransaminase 27 ± 13 versus 27 ± 10 IU/L (P = 0.81), gamma-glutamyl transferase 54 ± 138 versus 49 ± 35 IU/L (P = 0.72), Fatty Liver Index 58.9 ± 24.6 versus 61.2 ± 22.9 (P = 0.37), and Fibrosis-4 score 1.5 ± 0.6 versus 1.30 ± 0.6 (P = 0.51). Fatigue occurred in 25.3% of venesected patients versus 2.3% of controls (P < 0.0001). In the subgroup of patients who lost weight, glycemia, homeostasis model of assessment of insulin resistance, serum ferritin, lipid profile, and liver function tests improved irrespective of bloodletting. CONCLUSION In DIOS patients, iron depletion by bloodletting does not improve metabolic and hepatic features, is associated with weight gain, and is not as well tolerated as expected; sustained modification of diet and lifestyle habits remains the first therapeutic intervention in DIOS. (Hepatology 2017;65:465-474).
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Serum ferritin in HIV-positive patients is related to immune deficiency and inflammatory activity.
López-Calderón, C, Palacios, R, Cobo, A, Nuño, E, Ruiz, J, Márquez, M, Santos, J
International journal of STD & AIDS. 2015;(6):393-7
Abstract
To analyse the prevalence of high ferritin levels in asymptomatic HIV patients and its related factors we conducted a cross-sectional study of a cohort of HIV outpatients in regular follow-up. Epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about cardiovascular risk factors and underwent a physical examination and a 12-h fasting blood analysis. High ferritin levels were defined as a plasma ferritin level >200 µg/L in women and >300 µg/L in men. A total of 571 patients (78.1% men) were included. Median age was 43.2 years, HIV sexual transmission 68.5%, median CD4 count 474 cells/µL, 36.3% AIDS cases, 86.2% on antiretroviral therapy and 74.8% of them with undetectable viral load; 14.6% metabolic syndrome criteria, and mean cardiovascular risk at 10 years 6.67%. High ferritin levels prevalence was 11%, and related factors were a CD4 count <350 cells/µL (odds ratio, OR 2.37 [1.3-4.1], p = 0.003), ultrasensitive C-reactive protein >3 mg/L (OR 2.67 [1.5-4.7], p = 0.001) and chronic hepatitis C virus infection (OR 2.77 [1.5-4.9], p = 0.001). High ferritin levels are not uncommon in HIV patients, and they correlate with immunosuppression defined as CD4 count <350 cells/µL, higher ultrasensitive C-reactive protein and hepatitis C virus infection, and in contrast to the general population, they are not related to increased cardiovascular risk or metabolic syndrome.
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Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption.
Avila, F, Echeverría, G, Pérez, D, Martinez, C, Strobel, P, Castillo, O, Villaroel, L, Mezzano, D, Rozowski, J, Urquiaga, I, et al
Oxidative medicine and cellular longevity. 2015;:769739
Abstract
BACKGROUND AND AIMS Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. METHODS AND RESULTS Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), hepatic damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. CONCLUSION Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men.
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[Clinical evaluation of a hyperferritinemia].
Sogni, P, Buffet, C
Presse medicale (Paris, France : 1983). 2013;(4 Pt 1):405-10
Abstract
A hyperferritinemia has to be interpreted in relation with age and sex. The clinical evaluation begins with the interpretation of transferrine saturation which has to be controlled with a second fasting blood test. In case of high transferrine saturation associated with hyperferritinemia, HFE testing has first to be realized since the first diagnosis suspected is a HFE hemochromatosis. In case of normal transferrine saturation associated with a hyperferritinemia, the more frequent diagnosis is a metabolic syndrome, an inflammatory syndrome, a syndrome of cellular lysis or an excessive alcohol consumption. In case of HFE hemochromatosis, phlebotomy prevents complications. The goal is to obtain and to maintain a normal-low ferritin level. In case of metabolic syndrome, phlebotomy could be useful in case of high hepatic iron concentration measured with MRI or in case of on-alcoholic steato-hepatitis.
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[Dysmetabolic hyperferritinemia: a new target for treatment?].
Waeber, G, Vollenweider, P, Marques-Vidal, PM
Revue medicale suisse. 2013;(404):2002, 2004-7
Abstract
Dysmetabolic hyperferritinemia is currently the most frequent cause of elevated ferritin levels in the general population. Whether dysmetabolic hyperferritinemia is a cause or an effect of insulin resistance is still a matter of debate. Still, several findings have been well established: increased iron intake or elevated ferritin levels are individual risk factors for diabetes, metabolic syndrome or gestational diabetes. When in presence of dysmetabolic hyperferritinemia, a small number of randomized controlled trials have suggested that therapeutic measures aimed at reducing ferritin levels such as low red meat consumption, deferoxamin or therapeutic phlebotomies have shown a beneficial effect on glucose homeostasis, lipid profile and impaired hepatic markers observed in non-alcoholic steatohepatitis.