Increased Serum Ferritin Concentrations Research Articles

An 8-Week Vitamin D3–Fortified Fruit Drink Supplementation Increases Serum Ferritin Concentration: A Randomized Controlled Trial in Malaysian Women With Low Iron Stores

BackgroundThere is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. ObjectiveThe aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). DesignAn 8-week double-blind randomized controlled trial was conducted. Subjects/settingA total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. InterventionSubjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Main outcome measuresMeasurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. Statistical analysesA mixed model, repeated measures analysis of variance was used to analyze the intervention effect. ResultsAttrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ –1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. ConclusionsOur study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

Prognostic value of three iron deficiency definitions in patients with advanced heart failure

Abstract Background Iron deficiency (ID) is a common co-morbidity in patients with chronic heart failure (HF) and is an independent predictor of adverse prognosis including quality of life and exercise capacity (1-3). Intravenous iron replacement improves outcomes in HF patients including exercise capacity, quality of life, rate of HF hospitalisation and possibly mortality (1-4). Different definitions of ID are used in clinical practice. European HF guidelines define ID as a serum ferritin concentration of &amp;lt; 100 ng/ml, or a serum ferritin of concentration of 100-299 ng/ml with a transferrin saturation (TSAT) &amp;lt; 20% (5) because this definition was used in most trials of iron replacement in HF (1-3). However, other criteria to diagnose ID have been proposed based on comparison to the gold standard of bone marrow biopsy including serum iron ≤ 13 µmol/L and TSAT &amp;lt; 20% (6). Serum ferritin concentrations to diagnose ID has been criticised because inflammation can lead to increased serum ferritin concentrations even in patients who would fulfil ID criteria based on alternative definitions (7). Purpose The prognostic value of ID in patients with advanced HF, assessed for heart transplantation, is currently not well established. This patient population is characterised by relatively young age, single-organ pathology and prognosis is largely determined by the severity of heart disease rather than co-morbidities. In this study we investigated the prognostic value of various ID definitions in this patient cohort. Methods and Results Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as 1) serum ferritin concentration of &amp;lt; 100 ng/ml, or 100-299 ng/ml with transferrin saturation &amp;lt; 20% (guideline definition), 2) serum iron concentration ≤ 13 µmol/L, or 3) transferrin saturation &amp;lt; 20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. 801 patients were included, and the prevalence of ID was 39-55% depending on definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure [HR 1.532 (95% CI 1.264 - 1.944) and HR 1.595 (95% CI 1.323 - 2.033), respectively], but the same association was not seen with the guideline definition of ID [HR 1.085 (95% CI 0.8827 - 1.333)]. These findings were robust in multivariable cox regression analysis. ID, by all definitions, was associated with lower six-minute walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output. Conclusions ID, when defined by serum iron concentration or transferrin saturation was associated with increased frequency of adverse clinical outcomes in patients with advanced HF. The same association was not seen with guideline definition of ID.

Serum Ferritin: As a Biomarker in Diagnosis of Dengue Fever

Background: Major public health risk was ‘Dengue infection’ initial discovery is critical to improving the existence in serious infection of dengue. Our objective in this study was to investigate the serum ferritin level to suppose biomarker in the diagnosis of dengue fever. Method: An observational and prospective study was conducted in the Hayatabad Medical Complex and it included one hundred nineteen cases related to dengue was diagnosed by using NSI Test antigen or serology test related to specific dengue that internment “ELISA”. At the time of diagnosis, serum ferritin was measured. Monitoring the clinical and platelets counts was done on daily bases, it also classified into two groups such as non-severe and severe groups by allowing WHO criteria in 2009. Result: Five out of 119 cases of dengue were severe, dengue patients had lower platelets when they are in severe condition, count the number of platelets (p less than 0.0001); Ferritin level almost high (p=0.02) and the value of hospital longer time period (p less than 0.0001) mostly in severe group as compare to non-severe group of dengue. Platelets count had negative value with age factor almost Positive correlations with ferritin levels (p=0.08 or r= 0.16) and a longer hospital stay (r= -0.427 and p 0.0001) were also found (r= 0.26, p= 0.004). These values indicate the severe risk of dengue infection/ disease. Negative value of serum ferritin that are related to the value of platelets (r=0.51 and p&lt; 0.001). On day 4 of clinical infections, an elevated value of ferritin is seen in severe cases. Conclusion: In Clinical practice, a biomarker for determining the severity of dengue infection is increased serum ferritin concentrations. Keywords: Biomarkers, Serum ferritin, Severity, Dengue infection, Predicators

Cutoff Values for Serum Ferritin in Predicting Cirrhosis Severity due to Cholestatic Jaundice in Vietnamese Children.

Background:High serum ferritin levels are associated with liver cirrhosis severity and worse outcomes for hepatopathies. This study determined the serum ferritin cutoff values for predicting cirrhosis severity in children with cholestatic jaundice.Methods:A retrospective study was performed, including all cases diagnosed with cirrhosis in children aged 1 month to 16 years at Children’s Hospital 2-Vietnam between 2016 and 2021. Receiver operating characteristic (ROC) curve analysis was used to estimate ferritin cutoff values for predicting disease severity.Results:The study included 95 patients with cirrhosis due to cholestatic jaundice. Decompensated cirrhosis accounted for the majority (74.7%) of cases. Increased serum ferritin concentrations predicted cirrhosis severity in children, and the optimal ferritin cutoff value for predicting decompensated cirrhosis was determined to be 195 μg/l, resulting in a sensitivity of 65.22%, a specificity of 95.83%, and an area under the ROC curve (AUC) or 0.82. The Child–Pugh C group had higher ferritin levels than the Child–Pugh A and B group (p < 0.001), and the ferritin cutoff value for distinguishing between Child–Pugh classifications was 195 μg/l, resulting in a sensitivity of 71.2%, a specificity of 87.9%, and an AUC of 0.80.Conclusions:Serum ferritin levels are significantly associated with decompensated cirrhosis and disease severity (as assessed by Child–Pugh score). Routine serum ferritin testing may contribute to predicting cirrhosis severity in children.

To establish the role of serum ferritin as a prognostic marker in patients of stroke

Introduction: Stroke is the second leading cause of death worldwide. The incidence of cerebrovascular diseases increases with age. 1 Accurate prognostication of stroke patients is difficult many times. Materials and Methods: A total of 100 stroke patients who presented to R.N.T. Medical College Udaipur Rajasthan were enrolled from February 2016 to October 2016 and their serum ferritin was measured and correlated with early neurological deterioration in patients of acute stroke. Results: Total 100 patients were included, the age ranged from 22-90 years and the age group with the maximum number of patients was 61-70 years. 62 patients were in ischemic and 38 were in hemmoraghic groups. In ischemic group the mean serum ferritin level was 89.540 in clinically improvement patients and 341.345 in those deteriorated. In hemorrhagic group the mean serum ferritin level was 86.838 in clinically improvement patients and 355.759 in those deteriorated. Conclusion: The patients with stroke with increased serum ferritin concentrations have a higher risk of poor clinical outcome, hemorrhagic transformation, and brain edema than patients with low ferritin values. Keywords: Serum ferritin, Ischemic stroke, Hemorrhagic transformation.

A Randomized Trial of Iron-Biofortified Pearl Millet in School Children in India ,

Background: Iron deficiency is the most widespread nutritional deficiency in the world.Objective: The objective of this randomized efficacy trial was to determine the effects of iron-biofortified pearl millet (Fe-PM) on iron status compared with control pearl millet (Control-PM).Methods: A randomized trial of biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was conducted in 246 children (12–16 y) for 6 mo in Maharashtra, India. Iron status [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total body iron (TBI)], inflammation (C-reactive protein and α-1 acid glycoprotein), and anthropometric indices were evaluated at enrollment and after 4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe-PM on iron status compared with commercially available Control-PM. Linear and binomial regression models were used to evaluate the effects of Fe-PM on iron status and incidence of anemia and iron deficiency, compared with Control-PM.Results: At baseline, 41% of children were iron deficient (SF <15 μg/L) and 28% were anemic (hemoglobin <12.0 g/dL). Fe-PM significantly increased SF concentrations and TBI after 4 mo compared with Control-PM. Among children who were iron deficient at baseline, those who received Fe-PM were 1.64 times more likely to become iron replete by 6 mo than were those receiving Control-PM (RR: 1.64, 95% CI: 1.07, 2.49, P = 0.02). The effects of Fe-PM on iron status were greater among children who were iron deficient at baseline than among children who were not iron deficient at baseline.Conclusions: Fe-PM significantly improved iron status in children by 4 mo compared with Control-PM. This study demonstrated that feeding Fe-PM is an efficacious approach to improve iron status in school-age children and it should be further evaluated for effectiveness in a broader population context. This trial was registered at clinicaltrials.gov as NCT02152150.

Hyperferritinemia and markers of inflammation and oxidative stress in the cord blood of HIV-exposed, uninfected (HEU) infants.

The purpose of this study was to evaluate markers of iron status and inflammation/oxidative stress in maternal and cord blood (CB) of HIV-infected and HIV-uninfected women as potential mechanisms for poor outcomes among HIV-exposed, uninfected (HEU) infants. Maternal venous blood and CB specimens were obtained from 87 pregnant women (45 HIV-infected and 42 HIV-uninfected) enrolled at Kalafong Hospital, Pretoria, South Africa. Iron status [serum iron, ferritin and transferrin concentrations, transferrin saturation, soluble transferrin receptor (sTfR) concentration and the sTfR/log ferritin (sTfR/F) index], antenatal exposure to inflammation (CB C-reactive protein and interleukin-6 concentrations and haptoglobin switch-on status) and oxidative stress [total radical trapping ability of CB plasma (TRAP) and chronic oxidative stress (soluble receptor of advanced glycation end-products (sRAGE) concentration] were assessed in laboratory studies. There were no differences between the HIV-infected and HIV-uninfected groups in maternal haematological and iron indices, except that HIV-infected mothers had decreased white blood cell counts (P = 0.048) and increased serum ferritin concentrations (P = 0.032). Ferritin levels were significantly higher in CB than in maternal blood (P < 0.001) in both groups and further elevated in the CB of HEU infants (P = 0.044). There was also an inverse relationship between CB sTfR/F index and sRAGE (r = -0.43; P = 0.003) in the HIV-infected but not in the HIV-uninfected group. Our study showed for the first time that ferritin was significantly elevated in CB of HEU infants. The inverse relationship between sTfR/F index and sRAGE in CB suggests that chronic oxidative stress or RAGE axis activation in HIV-infected mothers may play a role in modulating ferritin levels.

Carbon monoxide and iron modulate plasmatic coagulation in Alzheimer's disease.

Alzheimer's disease (AD) is a significant source of morbidity and mortality for millions of people worldwide, and multiple potential etiologies have been postulated to contribute to AD. Among these, spontaneous cerebral emboli and increased cerebral and circulating heme oxygenase (Hmox) activity in AD patients are of particular interest, as two of the products of Hmox activity, carbon monoxide (CO) and iron enhance plasmatic coagulation and modify the ultrastructure of thrombi. We hypothesized that patients afflicted with AD would have coagulation kinetics modulated by CO and iron. Using viscoelastic assessments of coagulation, it was determined with a small cohort (n=11) of AD patients that all had enhancement of coagulation by CO, iron, or both. In a complementary fashion, it was determined that a separate cohort (n=12) of AD patients had thrombi with ultrastructural features consistent with iron and CO exposure as assessed with scanning electron microscopy. Further, when stratified by normal or abnormally increased serum ferritin concentrations (which can be increased by Hmox), the AD patients with abnormal ferritin concentrations had significantly thinner fibrin fiber diameters, not unlike that noted when normal plasma is mixed with iron or CO. In sum, AD patients were noted to have plasmatic coagulation kinetic and thrombus ultrastructural changes consistent with exposure to CO and iron. Future investigation of CO and iron in the pathogenesis of Alzheimer's disease is warranted.

Hepatic magnetic resonance imaging with T2* mapping of ovariectomized rats: correlation between iron overload and postmenopausal osteoporosis.

To explore the correlation between liver iron overload and bone mineral density (BMD) in an ovariectomy (OVX) rat model, using liver magnetic resonance (MR)-T2* and dual-energy X-ray absorptiometry (DEXA). Sprague-Dawley rats received deferoxamine (DFO) or phosphate-buffered saline 3 months after bilateral OVX. MRI and DEXA were performed pre- and postoperatively. Five rats per group were killed every month for micro-CT, histopathology and biochemical examinations. Statistical analysis was performed with independent-samples t tests, box plots and Pearson's correlation analysis. At 2 months postoperatively, BMD was significantly lower in the OVX group than in the control group (P < 0.01), corresponding to the increased serum ferritin concentration (SFC; P < 0.01) and liver iron concentration (LIC; P < 0.01). Liver T2* values significantly differed between the two groups at 1 month postoperatively (P < 0.001) and improved 1 month after DFO injection (P < 0.05). These values were significantly and positively correlated with BMD in the control (r = 0.527, P < 0.001) and OVX (r = 0.456, P < 0.001) groups. Liver MRI T2* changed markedly earlier than BMD, LIC and SFC, and correlated well with osteoporosis; it may thus be a valuable early indicator of osteoporosis. • Iron overload plays a vital role in the pathogenesis of postmenopausal osteoporosis. • Liver T2* relaxation time is a sensitive value in reflecting iron overload. • Liver T2* mapping elucidates changes in postmenopausal osteoporosis earlier than BMD. • Iron chelation increases BMD in ovariectomized rats. • Liver T2* has a moderate positive correlation with BMD.

Association between Serum Ferritin Levels and Risk of the Metabolic Syndrome in Chinese Adults: A Population Study

Ferritin is a ubiquitous intracellular protein that can store and release iron and act as a buffer against iron deficiency and iron overload. Ferritin is widely used as a clinical biomarker to evaluate iron status. Increased serum ferritin concentrations have been reported to be associated with metabolic syndrome (MetS) features. However, serum ferritin concentrations differ significantly according to sex and ethnicity, and the data concerning the relationship between serum ferritin concentrations and MetS in Asian men and women are conflicting. This study aimed to explore the relationship between serum ferritin and MetS in Chinese population. Fasting blood samples and anthropometric data collected on 8,441 adults aged 18 and older in 2009 as part of the China Health and Nutrition Survey, a large-scale longitudinal, household-based survey in China. Data was collected by trained physicians and biomarkers were measured with Hitachi Clinical Autoanalyzer 7600 D model and P model. Median levels of serum ferritin were significantly higher in men compared with women (121.9 vs. 51.0 ng/ml, P < 0.001), and significantly lower in non metabolic syndrome population with MetS population (73.2 vs. 106.0 ng/ml, P < 0.001). The difference remained significant after further adjusted for age, nationality, Body mass index (BMI), smoking status, and alcohol consumption. For both men and women, the highest prevalence of MetS occurred in the highest quartile of serum ferritin. The odds ratios increased progressively across the ferritin quartiles (P<0.001 for trend). Increased serum ferritin concentrations are associated with the metabolic syndrome among men and women in China.

Eficacia del hierro aminoquelado en comparación con el sulfato ferroso como fortificante de un complemento alimentario en preescolares con deficiencia de hierro. Medellín, 2011

Iron depleted deposits are the first link in the chain of events leading to iron deficiency which is the most prevalent nutritional shortage and main cause of anemia worldwide. This situation can be prevented through food fortification. To compare the efficacy of amino acid chelate iron with ferrous sulfate as fortifier of a dietary complement in preschoolers with iron deficiency. This study was a blinded clinical trial with randomized groups. We analyzed 56 preschoolers with iron deficiency (ferritin < 24 ng/ml) that received 13 g of milk with 12.5 mg of iron, either amino acid chelate or in the ferrous sulfate form. After two months, hemoglobin, hematocrit and serum ferritin concentrations were measured. In the ferrous sulfate group, ferritin concentration increased from 18.8 ng/ml to 24.1 ng/ml, while the variation was of 18.4 ng/ml to 29.7 ng/ml in the amino acid chelate group, with statistically differences in both cases. Serum ferritin was different between groups, being higher in iron amino acid chelate group (p=0.022). Hemoglobin and hematocrit levels did not change after the intervention. Adverse reactions in the ferrous sulfate group were 35.7%, compared with 42.9% in the iron amino acid chelate group; 5 children had respiratory tract infection, without statistical differences. Both compounds increased serum ferritin concentration, with a higher increase in those who were given milk with iron amino acid chelate. There were no differences in the adverse reactions and infections incidences between the groups.

Hyperferritinemia in Dogs with Splenic Hemangiosarcoma

ABSTRACTSerum ferritin concentration increases in dogs in association with various diseases. In this study, we measured serum ferritin levels in dogs with splenic masses, using a sandwich ELISA assay. Eleven dogs with hemangiosarcoma (HSA), six with hematoma, 1 with hemangioma and 3 with lymphoma were enrolled. All dogs with HSA had serum ferritin concentrations above the normal limit (1,357 ng/ml, mean + 2× standard deviation of normal). Increased serum ferritin concentrations have also been observed in few cases of hematoma, hemangioma and lymphoma. Therefore, hyperferritinemia is not specific for splenic HSA, but may have clinical usefulness as a sensitive test for the disease. Further evaluation of serum ferritin concentrations in dogs with splenic HSA is needed.

Serum ferritin level is associated with the prevalence of metabolic syndrome in Korean adults: The 2007–2008 Korean National Health and Nutrition Examination Survey

BackgroundIncreased ferritin concentrations, which reflect body iron stores, contribute to insulin dysfunction and metabolic syndrome (MetS). MethodsThis cross-sectional study included 7346 subjects (3229 men and 4117 women) who participated in the 2007–2008 Korean National Health and Nutrition Examination Survey (KNHANES). We adopted the modified Asian criteria for MetS from the American Heart Association/National Heart, Lung, and Blood Institute. ResultsIn comparison with participants in the first serum ferritin quartile, the odds ratio (95% confidence interval) for MetS for participants in the fourth serum ferritin quartile was 1.67 (1.24–2.23) in men and 1.41 (1.06-1.88) in women after adjusting for multiple covariates (including menopausal status in women) except insulin resistance. This association was attenuated, however, after additionally adjusting for insulin resistance [1.46 (1.08–1.98) in men and 1.22 (0.91–1.65) in women]. In particular, higher serum ferritin concentrations were associated with increased triglyceride concentrations in men and glucose intolerance in women. ConclusionsIncreased serum ferritin level was positively associated with the prevalence of MetS and with some diagnostic components of MetS, i.e., we found that increased serum ferritin concentrations were associated with high triglyceride and glucose concentrations in men and women, respectively.

P2-351 Iron status and cardiovascular disease risk in black South African women: the pure study

ObjectiveTo examine the associations between measures of iron status and cardiovascular disease (CVD) risk factors in South African women.DesignThe study was cross-sectional in design. Demographic information and health history were...

Use of glycosylated ferritin assay to aid the diagnosis of adult-onset Still’s disease: a local laboratory experience in Hong Kong

Adult-onset Still’s disease (AOSD) is a multi-systemic inXammatory disorder aVecting all ethnic groups. Even though there are several published diagnostic criteria, AOSD remains diYcult to diagnose clinically due to the overlapping features with infective, neoplastic and other rheumatological conditions [1, 2]. The problem is further complicated by the fact that treatments for AOSD, including steroid and immunosuppressive agents, can worsen the clinical course of the above conditions. Regarding laboratory markers, a markedly increased serum ferritin concentration is a common diagnostic marker among AOSD patients in active disease [3–5]. Generally speaking, serum ferritin concentration above 2,000 g/L is considered to be consistent with AOSD. Fautrel et al. [6] reported that a Wvefold increase in serum ferritin over upper limit of normal had 80% sensitivity and 41% speciWcity for AOSD. As marked elevation of serum ferritin concentration can also be seen in other disorders, the low speciWcity limits its diagnostic use. The percentage of glycosylated ferritin (GF), an isoform of ferritin, over total ferritin oVers additional diagnostic value. In healthy participants, 50–80% of ferritin is glycosylated. In inXammatory diseases, the glycosylated portion drops to 20–50%, while in AOSD, it is often ·20%. Using ·20% as the cut-oV, the sensitivity and speciWcity of percentage GF for AOSD were 80 and 66%, respectively. The combination of a percentage GF · 20% with ferritin over Wve times of normal produced a sensitivity of 43% and speciWcity of 93% [6]. We decided to develop an assay for the measurement of serum GF. Based on method described by Vignes et al. [7], GF could be easily separated from non-glycosylated ferritin by dividing the target serum sample into two aliquots, adding concanavalin A (Con-A) Sepharose 4B to one aliquot and only Sepharose 4B to the other aliquot and incubating them in a water bath for 2 h at room temperature. GF bound to Con-A, whereas non-glycosylated ferritin did not. The two aliquots were then centrifuged at 3,000 rpm for 15 min. The non-glycosylated ferritin unbound to Con-A was recovered in the supernatant and measured by immunometric assay. Accordingly, the non-glycosylated ferritin and total ferritin concentrations could be determined in the aliquots with Con-A Sepharose 4B and Sepharose 4B, respectively. The percentage GF was calculated from the diVerence between total ferritin and non-glycosylated ferritin divided by total ferritin. We had retrospectively analysed archived serum samples taken on admission from 5 newly diagnosed AOSD patients referred to our laboratory, in whom diagnosis was made clinically according to the Yamaguchi’s criteria. These 5 patients had serum ferritin concentrations of 8,047–41,479 g/L and percentage GF of 1.9–16.2%. The combined results were compatible with the diagnosis of AOSD. We had also randomly selected 15 patient samples with ferritin level over 2,000 g/L. These were patients with chronic anaemia requiring regular transfusion and patients with fulminant sepsis. Their serum ferritin concentrations ranged from 2,092 to 13,773 g/L and percentage GF varies from 28.6 to 80.6%. J. S.-S. Kwok (&) · M. H.-M. Chan Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China e-mail: jeffreykwok@cuhk.edu.hk

The relationship between indices of iron status and selected anthropometric cardiovascular disease risk markers in an African population: the THUSA study.

There is evidence that certain indices of iron status are associated with anthropometric measures, which are used independently as markers of cardiovascular disease (CVD) risk. This study examined whether this association exists in an African population. The study was a cross-sectional comparative study that examined a total of 1 854 African participants. Ferritin was positively associated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), percentage body fat and subscapular skinfold thickness. Serum ferritin concentration was higher in the high-WHR category than the normal-WHR category for both genders. Additionally, WC and WHR increased with increasing ferritin concentrations in both genders. Serum iron was lower in the obese than the normal-weight and pre-obese women only. In this population-based study, increased serum ferritin concentrations associated positively with increased WHR and WC, indicating that individuals or populations at risk of iron overload as defined by high serum ferritin concentrations may be at a greater risk of developing CVD.

Iron status and cardiovascular disease risk in black South African women: the PURE study

Objective: To examine the associations between measures of iron status and cardiovascular disease (CVD) risk factors in South African women.Method: In a cross-sectional study, demographic information and health history were obtained during individual interviews using validated questionnaires in the North West Province, South Africa. Anthropometric indices, iron indices, blood pressure, blood glucose and lipid profiles were measured using standard procedures in 1 262 apparently healthy black South African women aged 35 years or older. Iron status was assessed using serum concentrations of ferritin, transferrin receptor (TfR) and TfR:ferritin ratio.Results: Associations between iron status parameters and CVD risk factors were generally weak (r < 0.3, p < 0.01) and were not retained when adjustment was made for age, body mass index, smoking, alcohol consumption and C-reactive protein in the analysis. Waist circumference (WC) and waist:hip ratio (WHR) were higher in the fourth quartile of serum ferritin than in the third quartile, and also in the third quartile compared to the second quartile (P < 0.05). Based on WC and WHR respectively, 31% and 52% of the women had excess abdominal obesity. The mean (95% confidence interval) serum TfR concentration was high, at 9.09 µg/ml (8.77, 9.44), indicating risk of iron deficiency. The mean (95% confidence interval) concentrations of lipids [total cholesterol 4.78 mmol/l (4.64, 4.93), high-density lipoprotein cholesterol 1.45 mmol/l (1.39, 1.52), low-density lipoprotein cholesterol 1.65 mmol/l (1.53, 1.78), triglyceride 1.12 mmol/l (1.07, 1.18)] were within reference ranges.Conclusion: No significant association was found between iron status parameters and established CVD risk factors. However, excessive abdominal adiposity indicated by high WC and WHR contributes significantly to increased serum ferritin concentration in this population.

Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women

Increased serum ferritin concentrations in nonpathologic conditions, reflecting subclinical iron overload, have been reported to be associated with insulin resistance and an increased risk of type 2 diabetes mellitus (DM). However, serum ferritin concentrations differ significantly according to sex and ethnicity; and data concerning the relationship between serum ferritin concentrations and glucose metabolism abnormalities in Asian men and women are conflicting. This cross-sectional study investigated the association of serum ferritin concentrations with insulin resistance and impaired glucose metabolism in a large number of subjects with normal fasting glucose (NFG) level, impaired fasting glucose (IFG) level, or type 2 DM. We analyzed clinical and laboratory data from 12 090 subjects (6378 men and 5712 women; age, 20-89 years) who underwent general medical checkups. The study population included 1054 subjects with type 2 DM, 3783 subjects with IFG level, and 7253 subjects with NFG level. Serum ferritin, hemoglobin A 1c, fasting glucose, lipid, and insulin levels were measured. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. Serum ferritin concentrations were highest in the DM group, followed by the IFG group and the NFG group, in both men and women (186 ± 127, 176 ± 108, and 156 ± 92 ng/mL, respectively, in men; 85 ± 62, 75 ± 55, and 59 ± 47 ng/mL, respectively, in women). After adjustment for other variables using multiple regression analysis, homeostasis model assessment of insulin resistance was independently associated with serum ferritin concentration in men, but not in women. When the fourth quartile of ferritin was compared with the first quartile, the age-adjusted odds ratio (OR) for type 2 DM was 1.71 (95% confidence interval, 1.38-2.12) in men and 1.50 (1.05-2.13) in women. The OR in men was attenuated to 1.27 (1.01-1.60) but remained significant after adjustment for body mass index (BMI), waist circumference, blood pressure, serum lipids, liver enzymes, and high-sensitivity C-reactive protein (hsCRP). In nondiabetic subjects, the age-adjusted OR for IFG in the fourth quartile of ferritin was 1.82 (1.56-2.13) in men and 1.68 (1.40-2.02) in women. The OR was attenuated to 1.31 (1.11-1.55) in men and 1.45 (1.19-1.78) in women after adjustment for BMI, waist circumference, blood pressure, serum lipids, liver enzymes, and hsCRP. In NFG subjects, the age-adjusted OR for metabolic syndrome in the fourth quartile of ferritin concentration was 2.85 (1.99-4.07) in men and 1.21 (0.82-1.79) in women. In men, the OR was attenuated to 1.58 (1.06-2.37) after adjustment for BMI, liver enzymes, and hsCRP. Increased serum concentrations of ferritin are associated with insulin resistance, type 2 DM, IFG, and metabolic syndrome in men, but only with IFG in women. These results suggest that iron overload is associated with insulin resistance in men, but not in women.

Serum ferritin is a major determinant of lipid phenotype in familial combined hyperlipidemia and familial hypertriglyceridemia

Familial combined hyperlipidemia (FCH) and familial hypertriglyceridemia (FHTG) share pathogenic mechanisms and a high interaction with components of the metabolic syndrome. The metabolic syndrome associates increased serum ferritin concentration and high cardiovascular risk. The objective was to describe the frequency of iron overload and the relationship between serum ferritin and the phenotype in patients with FCH and FHTG. The study was composed of 211 consecutive unrelated patients aged at least 18 years with primary hypertriglyceridemia, 149 with FCH, and 62 with FHTG. The prevalence of the metabolic syndrome and hyperferritinemia was very high in both hypertriglyceridemic groups (51.7% and 20.1% in FCH and 62.9% and 16.1% in FHTG, respectively), without significant statistical differences between them. Serum ferritin concentration did not show any significant association with the number of metabolic syndrome criteria. Subjects in the highest tertile of ferritin concentration (ferritin >200 μg/L) presented higher concentrations of triglycerides and liver enzymes than subjects in the first tertile of ferritin concentration (ferritin <90 μg/L). The highest positive correlation coefficient for triglycerides was found with ferritin in FCH and in FHTG subjects ( R = 0.317 [ P < .001] when combined). Ferritin was also the covariate that showed the highest independent association with triglycerides in FCH and FHTG. In contrast, ferritin was not associated with carotid intima-media thickness. In summary, serum ferritin is commonly increased in FCH and in FHTG, it is not related with the presence of metabolic syndrome, and it is highly correlated with liver enzymes.

Effects of Cardiorespiratory Fitness on Serum Ferritin Concentration and Incidence of Type 2 Diabetes: Evidence from the Aerobics Center Longitudinal Study (ACLS)

Cardiorespiratory fitness (CRF) and physical activity (PA) are inversely related to the occurrence of type 2 diabetes (T2D). Both play an important role in reducing serum ferritin (SF) concentration. Increased SF concentration is considered a contributing factor for developing T2D. The present cohort study investigated 5,512 adult participants enrolled in the Aerobics Center Longitudinal Study (ACLS) between 1995 and 2001. The subjects completed a comprehensive medical examination and a SF evaluation, and had been followed up until either diabetes onset, death, or the cut-off date of November 2007. Three CRF levels were categorized. SF quartile levels were defined by gender and menopausal status. The incidence of T2D was calculated for 10,000 person-years, and hazard ratios (HR) were computed to predict the incidence of T2D based on SF quartiles and CRF levels. SF concentration was significantly higher in males than in females (148.5 +/- 104.7 ng/ml vs. 52.2 +/- 45.9 ng/ml) and was inversely associated with CRF levels. In the high CRF group, 32.7% of participants had a low SF concentration whereas only 16.8% of participants had a high SF concentration level. After adjusting for potential confounders, male participants in the highest SF quartile level had a 1.7 times (HR: 1.67, 95% CI: 1.05, 2.66; p-trend = 0.027) increased risk for developing T2D compared with those in the lowest SF quartile group. Lower SF concentration was associated with lower risk of developing T2D in those regularly participating in CRF. The findings from this study suggest that SF concentration could be used as a diabetic predictor. Based on these results clinicians and public health professionals should promote regular physical activity or fitness to reduce the incidence of T2D.