Comparison of test performance of two commonly used multiplex assays to measure micronutrient and inflammatory markers in serum: results from a survey among pregnant women in South Africa.

The combined sandwich-ELISA (s-ELISA; VitMin Lab, Germany) and the Quansys Q-Plex™ Human Micronutrient Array (7-Plex) are multiplex serum assays that are used to assess population micronutrient status in low-income countries. We aimed to compare the agreement of five analytes, α-1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin, retinol-binding protein 4 (RBP4) and soluble transferrin receptor (sTfR) as measured by the 7-Plex and the s-ELISA. Serum samples were collected between March 2016 and December 2017. Pregnant women (n 249) were recruited at primary healthcare clinics in Johannesburg, and serum samples were collected between March 2016 and December 2017. Agreement between continuous measurements was assessed by Bland-Altman plots and concordance measures. Agreement in classifications of deficiency or inflammation was assessed by Cohen's kappa. Strong correlations (r > 0·80) were observed between the 7-Plex and s-ELISA for CRP and ferritin. Except for CRP, the 7-Plex assay gave consistently higher measurements than the s-ELISA. With the exception of CRP (Lin's ρ = 0·92), there was poor agreement between the two assays, with Lin's ρ < 0·90. Discrepancies of test results difference between methods increased as the serum concentrations rose. Cohen's kappa for all the five analytes was < 0·81 and ranged from slight agreement (vitamin A deficiency) to substantial (inflammation and Fe deficiency) agreement. The 7-Plex 1.0 is a research and or surveillance tool with potential for use in low-resource laboratories but cannot be used interchangeably with the s-ELISA. Further optimising and validation is required to establish its interchangeability with other validated methods.

Biological variation of inflammatory and iron metabolism markers in high-endurance recreational athletes; are these markers useful for athlete monitoring?

OBJECTIVES: To deliver biological variation (BV) data for serum hepcidin, soluble transferrin receptor (sTfR), erythropoietin (EPO) and interleukin 6 (IL-6) in a population of well-characterized high-endurance athletes, and to evaluate the potential influence of exercise and health-related factors on the BV. METHODS: Thirty triathletes (15 females) were sampled monthly (11 months). All samples were analyzed in duplicate and BV estimates were delivered by Bayesian and ANOVA methods. A linear mixed model was applied to study the effect of factors related to exercise, health, and sampling intervals on the BV estimates. RESULTS: Within-subject BV estimates (CVI) were for hepcidin 51.9 % (95 % credibility interval 46.9-58.1), sTfR 10.3 % (8.8-12) and EPO 27.3 % (24.8-30.3). The mean concentrations were significantly different between sex, but CVI estimates were similar and not influenced by exercise, health-related factors, or sampling intervals. The data were homogeneously distributed for EPO but not for hepcidin or sTfR. IL-6 results were mostly below the limit of detection. Factors related to exercise, health, and sampling intervals did not influence the BV estimates. CONCLUSIONS: This study provides, for the first time, BV data for EPO, derived from a cohort of well-characterized endurance athletes and indicates that EPO is a good candidate for athlete follow-up. The application of the Bayesian method to deliver BV data illustrates that for hepcidin and sTfR, BV data are heterogeneously distributed and using a mean BV estimate may not be appropriate when using BV data for laboratory and clinical applications.

Iron status determined changes in health measures induced by nordic walking with time-restricted eating in older adults- a randomised trial.

BACKGROUND AND AIMS: This study evaluated whether stored iron determines the adaptive response induced by Nordic walking (NW) training combined with 10 hours' time-restricted eating (TRE) in older adults. TRIAL DESIGN AND METHODS: Twenty-four participants underwent 12-week NW training supported by 10 h of TRE. The group was divided due to baseline ferritin concentration low < 75 ng/ml (LF) and high level ≥ 75 ng/ml (HF). Body composition, physical fitness and blood collection were assessed at baseline and post-intervention. RESULTS: NW + TRE induced a statistically significant decrease in ferritin levels in all participants (p = 0.01). Additionally, statistically significant intergroup differences in the LF vs. HF in the reduction of serum ferritin levels (p = 0.04) were observed. The procedure NW + TRE diminished HbA1c levels (p < 0.01) and glucose in all participants (p = 0.05). The range of HbA1c drop was more pronounced among those participants who experienced a greater decrease in the stored iron (p = 0.04, [Formula: see text]=0.17, F=4.59). Greater changes in body weight and percent of body fat were recorded in the HF group (for both p<0.01). CONCLUSION: Body iron stores determine the effects of a 12-week NW + TRE intervention on serum ferritin. The changes in HbA1c are more pronounced in subjects with a higher decrease in serum ferritin. TRIAL REGISTRATION: All experimental protocols were approved by the Bioethical Committee of the Regional Medical Society in Gdansk, Poland (NKBBN/330/2021) according to the Declaration of Helsinki. We confirm that all methods were carried out in accordance with relevant guidelines and regulations. The trial was registered as a clinical trial (NCT05229835, date of first registration: 14/01/2022, direct link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05229835 ). Informed consent was obtained from all subjects.

Assessment of WHO 07/202 reference material and human serum pools for commutability and for the potential to reduce variability among soluble transferrin receptor assays.

OBJECTIVES: The clinical use of soluble transferrin receptor (sTfR) as an iron status indicator is hindered by a lack of assay standardization and common reference ranges and decision thresholds. In 2009, the WHO and National Institute for Biological Standards and Controls (NIBSC) released a sTfR reference material (RM), 07/202, for assay standardization; however, a comprehensive, formal commutability study was not conducted. METHODS: This study evaluated the commutability of WHO 07/202 sTfR RM and human serum pools and the impacts of their use as common calibrators. Commutability was assessed for six different measurement procedures (MPs). Serum pools were prepared according to updated CLSI C37-A procedures (C37) or non-C37 procedures. The study design and analyses were based on Parts 2 and 3 of the 2018 IFCC Commutability in Metrological Traceability Working Group's Recommendations for Commutability Assessment. WHO 07/202 and serum pools were used for instrument/assay and mathematical recalibration, respectively, to determine if their use decreases inter-assay measurement variability for clinical samples. RESULTS: The WHO 07/202 RM dilutions were commutable for all 6 MPs assessed and, when used for instrument calibration, decreased inter-assay variability from 208 to 55.7 %. Non-C37 and C37 serum pools were commutable for all 6 MPs assessed and decreased inter-assay variability from 208 to 13.8 % and 4.6 %, respectively, when used for mathematical recalibration. CONCLUSIONS: All materials evaluated, when used as common calibrators, substantially decreased inter-assay sTfR measurement variability. MP calibration to non-C37 and C37 serum pools may reduce the sTfR IMPBR to a greater extent than WHO 07/202 RM.

Elevated Serum Levels of Soluble Transferrin Receptor Are Associated with an Increased Risk of Cardiovascular, Pulmonary, and Hematological Manifestations and a Decreased Risk of Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients.

The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and the disease activity and organ manifestations in SLE patients. We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. The median serum levels of sTfR (p > 0.000001) and IL-4 (p < 0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p < 0.0001), a lower iron concentration (p = 0.008), a lower value of total iron-binding capacity (TIBC) (p = 0.03), and lower counts of RBC (p = 0.004), HCT (p = 0.0004), PLT (p = 0.04), neutrophil (p = 0.04), and lymphocyte (p < 0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p = 0.0005), HGB (p = 0.0001) and HCT (p = 0.008), and positively correlated with IL-4 (p = 0.01). Elevated serum sTfR > 2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71-464.78; p = 0.001), ischemic heart disease (OR: 3.25 95 CI 1.02-10.40; p = 0.04), lung manifestations (OR: 4.48 95 CI 1.44-13.94; p = 0.01), and hematological manifestations (OR: 2.07 95 CI 1.13-3.79; p = 0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22-0.80; p = 0.008). Serum IL-4 was negatively correlated with CRP (p = 0.003), and elevated serum IL-4 levels > 0.17 mg/L were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26-0.90; p = 0.02). In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

[Iron store status of children aged 6 to 17 years in Beijing in 2016-2017].

OBJECTIVE: To quantitatively assess the concentration and distribution of body iron(BI) in children aged 6 to 17 years in Beijing. METHODS: A total of 1392 children aged 6 to 17 years in Beijing were randomly selected for questionnaire survey and physical examination in 2016-2017. Fasting venous blood was collected, serum ferritin(SF) and serum soluble transferrin receptor(sTfR) were measured by immunoturbidimetric assay. BI were calculated, and the concentration and distribution of BI in children aged 6 to 17 years was assessed. RESULTS: The average BI level of children aged 6 to 17 in Beijing was(5.49±2.94) mg/kg. The average BI level of boys was higher than that of girls, and the average BI level of children with abdominal obesity was higher than that of children without abdominal obesity, and the differences were statistically significant(P<0.05). The concentration of BI in children aged 6 to 17 years in Beijing was 4-7.99 mg/kg, accounting for the highest proportion(57.3%). The concentration of BI<0 mg/kg accounted for the lowest proportion(4.3%). There were significant differences in the distribution of BI concentration in different gender, age and abdominal obesity(P<0.05). The anemia rate of children aged 6 to 17 in Beijing was 2.7%(95%CI 1.9-3.6), the low ferritin rate(SF<25 µg/L) was 22.5%(95%CI 20.0-24.8), and the iron deficiency rate(SF<15 µg/L) was 7.8%(95%CI 6.4-9.3), the negative iron stores(BI<0 mg/kg) rate was 4.3%(95%CI 3.2-5.3). The anemia rate, low ferritin rate, iron deficiency rate and negative iron stores rate were higher in girls than boys, and higher in children aged 12 to 17 years than in children aged 6 to 11 years, and the differences were statistically significant(P<0.01). CONCLUSION: Iron deficiency was still present in children aged 6 to 17 in Beijing from 2016 to 2017. The proportion of low BI level in girls and children aged 12 to 17 is higher, respectively.

Relationship Between Soluble Transferrin Receptor and Clinical Outcomes in Patients With Heart Failure According to Ejection Fraction Phenotype: The New Zealand PEOPLE Study.

BACKGROUND: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) but its impact on prognosis in HF with preserved ejection fraction (HFpEF) remains unclear. We assessed whether ID defined by soluble transferrin receptor (sTfR) criteria is independently associated with all-cause mortality in patients with HFpEF, and evaluated its comparative prognostic performance to ID definitions in common clinical use. METHODS AND RESULTS: Data were analyzed from 788 patients (36% HFpEF) in a prospective multicenter HF cohort study. Baseline plasma samples were analyzed with respect to 4 definitions of ID: sTfR of ≥1.59 mg/L (IDsTfR1), sTfR of ≥1.76 mg/L (IDsTfR2), ferritin of <100 µg/L, or ferritin of 100-300 µg/L + transferrin saturation of <20% (IDFerritin), and transferrin saturation of <20% (IDTsat). In multivariable Cox models IDsTfR2 (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.23-2.75) and IDTsat (HR, 1.69, 95% CI 1.10-2.59) were both independently associated with all-cause mortality in patients with HFpEF, whereas IDsTfR1 (HR 1.41, 95% CI 0.92-2.16) and IDFerritin (HR 1.19, 95% CI 0.77-1.85) were not. On inclusion of patients with HF with reduced EF, IDsTfR1 (HR 1.45, 95% CI 1.13-1.86) gained significance, but IDFerritin (HR 1.21, 95% CI 0.95-1.54) did not. For each pair of definitions intra-patient concordance was approximately 65%. CONCLUSION: ID defined by sTfR criteria is independently associated with all-cause mortality in patients with HFpEF. Poor concordance between ID definitions suggests that iron biomarkers do not reflect the same pathological process in the complex relationship between iron and HF. Therefore, which definition should guide iron replacement needs further evaluation.

The VitMin Lab Sandwich-ELISA Assays for Iron and Inflammation Markers Compared Well with Clinical Analyzer Reference-Type Assays in Subsamples of the Nepal National Micronutrient Status Survey.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6-59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin's ρ = 0.58). The median relative difference to the reference was as follows: Fer, -8.5%; sTfR, 71.2%; CRP, -19.5%; and AGP, -8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Conclusions: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Hepcidin and other indicators of iron status, by alpha-1 acid glycoprotein levels, in a cohort of Mexican infants.

The purpose of this study was to describe the changes in iron status indicators at 6 and 12 months of age, controlling by inflammation by measuring alpha-1 acid glycoprotein (AGP). This longitudinal study included 48 healthy-term singleton infants with birth weight ≥ 2500 g, born in hospitals of the Mexican Institute for Social Security. Complete blood count, ferritin, soluble transferrin receptor (sTfR), hepcidin, and AGP were measured in blood at 6 and 12 months of age. sTfR/ferritin ratio and total body iron (TBI) stores were calculated. Hemoglobin and sTfR/ferritin ratio increased with age, while ferritin and TBI decreased. In infants without inflammation, hepcidin, sTfR, and MVC did not show significant changes from 6 to 12 months of age, while ferritin and TBI decreased. In infants with inflammation, hepcidin, TBI, and ferritin levels increased, while hemoglobin and sTfR/ferritin ratio decreased. MVC and sTfR did not change significantly in the presence or absence of inflammation. Hepcidin concentration correlated positively and significantly with ferritin and TBI stores and showed significant negative correlation with sTfR/ferritin ratio. Our study showed that, in absence of inflammation and ID, during the first year of life, physiological changes occur in hemoglobin and ferritin levels as well as in indicators derived from ferritin and sTfR; in contrast, hepcidin and sTfR did not show significant change. However, hepcidin concentration was lower in infants with ID and was higher when inflammation was present, supporting that infants have a functional hepcidin response to changes in iron stores.

Diagnosing empty iron stores in women: unbound iron binding capacity (UIBC) versus soluble transferrin receptor (sTFR).

Unbound iron binding capacity (UIBC) is more accurate than total iron binding capacity (TIBC) and percent transferrin saturation in diagnosing empty iron stores. It is unknown whether UIBC is more or less accurate than soluble transferrin receptor (sTFR). We obtained public-use data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2006 to compare the accuray of UIBC and sTFR in diagnosing empty iron stores in 2337 women aged 12-49 years. We grouped the women according to CRP less than 5 mg/L and pregnancy (four groups) and used three definitions of empty iron stores: Serum ferritin less than 10, 15, and 20 µg/L. Receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic accuracy. UIBC showed a better diagnostic accuracy than sTFR in all groups and definitions of empty iron stores, except in nonpregnant women with CRP at least 5 mg/L when empty iron stores were defined as ferritin less than 10 and 15 µg/L. Two differences reached statistical significance: In nonpregnant women without inflammation the area under the ROC curve for UIBC was 0.830 compared to 0.793 for sTFR (p = .007) when empty iron stores were defined as ferritin less than 20 µg/L. The corresponding figures for pregnant women without inflammation were 0.843 for UIBC and 0.739 for sTFR (p = .003). In conclusion, UIBC is a more accurate test than sTFR in diagnosing empty iron stores in women without inflammation.

[Optimization of platform conditions for simultaneous detection of multiple nutritional marker proteins by liquid protein microarray].

OBJECTIVE: To optimize the technical conditions for simultaneous detection of serum ferritin(SF), soluble transferrin receptor(sTfR), C-reactive protein(CRP)and retinol-binding protein four(RBP4)by liquid protein microarray. METHODS: The trapping antibodies of the four proteins were coupled to magnetic beads with different codes, and the samples were added to the 96-well plate. The antibodies were detected by double antibody sandwich method. The serum of 5 patients were diluted with commercial diluent, 1% albumin from bovine serum(BSA) and phosphate buffer saline(PBS) to detect 4 target proteins, and the results were compared. The antibody specific binding ability was tested by antibody specific validation test. The interference between proteins was verified by the paired t test of the signal values of the single reaction system and the mixed reaction system. The lower limit of detection and the limit of biological detection of each protein were found by using multiple dilution method. The standard curve and regression equation were established. RESULTS: 1%BSA and PBS were selected to replace commercial diluent as diluents for the detection of 4 proteins in this experiment. The cross-reaction rate of the four antigens with other capture antibodies and detection antibodies was less than 2%. There was no significant difference in the signal value of each protein in the single reaction system and the mixed reaction system. The limit of detection and the limit of biological detection of SF were 1.155 and 1.625 ng/mL, respectively. The lower limit of detection and the limit of biological detection of sTfR were 2.682 and 5.208 ng/mL, respectively. The detection limit and biological detection limit of CRP were 0.302 and 0.391 ng/mL, respectively. The lower limit of detection and the limit of biological detection for RBP4 were 1.814 and 3.540 ng/mL, respectively. The standard curve and regression equation of the four proteins within the common linear range were as follows: SF y=172.5x-39.65, R~2=0.9968;sTfR y=60.10x+77.38, R~2=0.9972;CRP y=-6.000x~2+210.3x+246.1, R~2=0.9063;RBP4 y=-0.6998x~2+64.31x+134.8, R~2=0.9748. CONCLUSION: The conditions of the detection platform for four proteins such as SF, sTfR, CRP and RBP4 were optimized by using liquid protein chip technology.

Association of maternal hemoglobin and iron stores with neonatal hemoglobin and iron stores.

BACKGROUND: One of the commonest causes of anemia in pregnancy is iron deficiency. This study aims at understanding and exploring the association between fetal and maternal iron status. Predelivery maternal hemoglobin (Hb) and iron stores, serum iron, ferritin, and soluble transferrin receptor (sTfR), were assessed and compared to the cord blood Hb and iron stores with an attempt to identify the level of maternal Hb and ferritin at which the fetal iron stores reduce, helping to identify the neonates who will require earlier iron supplementation. METHOD: Four hundred eight participants were enrolled, and maternal and cord blood was collected at the time of delivery and tested for Hb and iron parameters. The results were statistically analyzed. RESULTS: Of all mothers, 27.2% mothers were anemic (Hb less than 11 g/dl). Of all newborns, 15.4% newborns had Hb less than 14 g/dl. There was a significant association between the maternal and cord blood iron, ferritin, sTfR and sTfR/log ferritin index. Eighty-five percent of the babies with cord blood Hb <14 g/dl had maternal serum ferritin (SF) <50 µg/L. Maternal SF <10 µg/l was associated with a significant number of babies with cord blood SF <75 µg/l (77.7%). One hundred sixty six neonates had sTfR 2 µg/ml or more. Of these, 80.7% had maternal SF <50 µg/l. Of the 115 newborns with a high sTfR/log ferritin index (>1.5), 56.5% had raised maternal sTfR (>2µg/ml). CONCLUSION: In view of a significant association between maternal and neonatal Hb and iron stores, newborns of mothers with iron deficiency anemia (IDA) during pregnancy should be monitored and followed up after birth for development of IDA and early iron supplementation.

Mean blood glucose-independent HbA1c racial disparity and iron status in youth with Type 1 DM.

INTRODUCTION: Black patients have higher HbA1c than Whites even after adjustment for mean blood glucose (MBG). Decreased iron status has been associated with increased HbA1c independently of glucose. We hypothesized that decreased iron status might account for higher HbA1c in Black patients. METHODS: Pediatric patients with T1D in the Diabetes Center at Children's Hospital of New Orleans who self-identified as either Black or White were recruited for the study. At the time of their clinic visit labs were obtained for ferritin (Fer), soluble transferrin receptor (sTfR), HbA1c, and CBC. MBG was derived from patient's home glucose meter records over the last 30 days. Total body iron (TBI) and sTfr/log10 Fer (R/lFer) were calculated. RESULTS: A total of 80 (35 Blacks/45 Whites; 41 female/39 male) patients were recruited. Unadjusted levels of HbA1c, MBG, sTfR, Fer, RDW-CV, and RDW-SD were all higher in Blacks than Whites. TBI and R/lFer were not different between groups. Fer was correlated with Hb, MBG but not HbA1c. sTfR was correlated with HbA1c, MCV, MCH, and RDW-SD. In multiple variable analysis with HbA1c as the dependent variable, race and MBG were statistically significant in the model. However, measures of iron status: Fer, sTfR, R/lFer and TBI were not statistically influential. CONCLUSION: After adjustment for race, MBG and RDW-CV, iron indices were not statistically significant independent predictors of HbA1c levels. These observations indicate that factors besides iron status and CBC indices contribute to MBG-independent racial disparity in HbA1c.

Associations of iron status with apolipoproteins and lipid ratios: a cross-sectional study from the China Health and Nutrition Survey.

BACKGROUND: Iron overload has been found to be related with various cardiometabolic disorders, like dyslipidemia, metabolic syndrome, and diabetes. The disturbance of the iron status and lipid metabolism can contribute to organ damage such as atherosclerotic plaque growth and instability. An assessment on the associations of iron status with apolipoproteins and lipid ratios would be informative for maintenance of metabolic homeostasis and hinderance of disease progression. Hence, this study aims to establish the relationships of iron status with apolipoproteins and lipid ratios. METHODS: A cross-sectional study of 7540 adult participants from the China Health and Nutrition Survey 2009 was conducted. Logistic regression analyses were used to investigate the relationships between indicators of iron status and the prevalence of unfavorable apolipoprotein profiles. Multivariate linear regression models were constructed to assess the dose-response correlations between serum ferritin and lipid parameters. RESULTS: After adjustment for confounding factors, in both sexes, the subjects in the top quartile of ferritin had the highest prevalence of an elevated apolipoprotein B (men: odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50-2.62; women: OR 2.13, 95% CI 1.53-2.97) and an elevated apolipoprotein B/apolipoprotein A1 ratio (men: OR 2.00, 95% CI 1.50-2.66; women: OR 1.41, 95% CI 1.04-1.92) when compared with individuals in the lowest quartile. Hemoglobin were also independently associated with unfavorable apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio both in men and women. However, transferrin (men: OR 0.74, 95% CI 0.56-0.99; women: OR 0.73, 95% CI 0.56-0.95) and soluble transferrin receptor (men: OR 0.75, 95% CI 0.57-0.99; women: OR 0.71, 95% CI 0.55-0.91) were found to be negatively associated with a decreased apolipoprotein A1. Moreover, after controlling for potential confounders, the ferritin concentrations were significantly associated with the levels of lipid ratios including TG/HDL-C, non-HDL-C/HDL-C, TC/HDL-C, apoB/apoA1, and LDL-C/HDL-C ratio in men (ß coefficient = 0.147, 0.061, 0.043, 0.038, 0.032, respectively, all P values < 0.001) and in women (ß coefficient = 0.074, 0.034, 0.025, 0.020, 0.018, respectively, all P values < 0.05). CONCLUSIONS: The indicators of iron status are significantly associated with unfavorable apolipoprotein profiles. Serum ferritin concentrations are positively correlated with the levels of lipid ratios. The management on the modifiable iron status and lipid metabolism has a clinical significance. The atherosclerotic lipid profiles of the patients with iron overload deserve special clinical concerns.

Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: A retrospective study.

BACKGROUND: Soluble transferrin receptor (sTfR) is a promising indicator of iron deficiency anemia (IDA). Here, we investigated the application value of sTfR assays based on three different methods for the diagnosis of IDA. METHODS: The sTfR concentrations in two groups of patient specimens with high-level and low-level sTfR concentrations and in quality control materials were measured four times a day for five consecutive days to evaluate the precision of the three methods. We selected patients with IDA, anemia of chronic disease (ACD), or chronic diseases with iron deficiency anemia (CIDA), and apparently healthy subjects, and measured the serum sTfR concentrations in all subjects using the three different methods. The cutoff points for an IDA diagnosis using the three assays and their corresponding clinical sensitivities and specificities were calculated by receiver operating characteristic analysis. RESULTS: For the diagnosis of IDA, the cutoff points of sTfR measured by the chemiluminescent, immunoturbidimetric, and immunonephelometric assays were 2.91, 6.70, and 2.48 mg/L, respectively. The corresponding sensitivities were 85.59%, 85.59%, and 85.59%, the specificities were 91.47%, 90.31%, and 90.70%, and area under the curve was 0.943, 0.944, and 0.936, respectively. The sTfR concentrations measured by the different methods were significantly higher in the IDA and CIDA groups than in the other two groups (P < .05). CONCLUSIONS: The sTfR based on the three different measurement methods presented promising analytical performances and met the clinical requirements for sensitivity and specificity. However, the different measurement methods had markedly different cutoff points for IDA diagnosis, which should be critically considered in clinical practice.

Characteristics of iron status, oxidation response, and DNA methylation profile in response to occupational iron oxide nanoparticles exposure.

Although the growing development and application of iron oxide nanoparticles (IONPs) may pose exposure risk and adverse health outcomes, biological changes due to occupational exposure remain unexplored. This cross-sectional study recruited 23 workers at a plant that manufactures IONPs and 23 age- and sex-matched controls without metal-rich occupational hazards exposure. Exposure metrics at worksites were monitored, and iron status, oxidation markers, and methylation profiles of genomic DNA in peripheral blood were measured using corresponding enzyme-linked immunosorbent assays and methylation-specific polymerase chain reaction (PCR), respectively. The mass concentration, number counting, and surface area concentration of airborne particles at the worksite significantly increased during the work process of manufacturing/handling IONPs. Overall, compared to controls, workers exhibited increased 5-hydroxymethylcytosine (5hmC) levels without changes in 5-methylcytosine (5mC), hepcidin methylation, iron, soluble transferrin receptor (sTfR), ferritin, hepcidin, 8-hydroxydeoxyguanosine, and glutathione. A positive correlation was found between 5hmC and IONP exposure year with adjustment for age, sex, and cotinine using partial correlation analyses (r = 0.521, p < 0.001). After stratification of INOPs exposure and 5hmC levels, the univariate general linear model with adjustment for age, sex, and cotinine found that the estimated mean levels of 5mC and sTfR in subjects with low and high 5hmC levels among controls were 11% and 14.4% (p ≤ 0.01) and 80.9 nM and 70.3 nM (p < 0.05), respectively. The estimated mean levels of sTfR in workers and controls with low 5hmC levels were 88.3 nM and 68.7 nM (p ≤ 0.01). Multivariate linear regression analyses suggested an association between sTfR and 5hmC (standardized ß = -0.420, p = 0.014) and female sex (standardized ß = 0.672, p < 0.001) for subjects with low 5hmC levels. These findings suggest that increased 5hmC could be differentially employed to monitor an epigenetic signature with steady iron homeostasis for occupational IONP-exposed individuals who are likely to experience early but specific decreased sTfR, especially for females concurrent with the onset of increment in 5hmC at low level.

Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial.

Abnormalities of iron homeostasis have been linked to insulin resistance, type 2 diabetes and cardiovascular disease. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to decrease serum iron and improve glucose metabolism in diabetic rodents. We have previously demonstrated that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese middle-aged adults. Yet, the impact of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included 26 participants, who were randomly allocated to receive 1 g carnosine (n = 14) or identical placebo (n = 12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays. Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference ± standard error: - 0.07 ± 0.03 mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. At follow-up, soluble transferrin receptor was associated inversely with urinary carnosine concentrations and positively with serum carnosinase-1 activity (both p < 0.02). Our findings suggest that carnosine may modulate iron metabolism in high-risk groups which could ameliorate insulin resistance and prevent type 2 diabetes. Larger human clinical trials are required to confirm our results.

Iron status and associations with physical performance during basic combat training in female New Zealand Army recruits.

Decreases in Fe status have been reported in military women during initial training periods of 8-10 weeks. The present study aimed to characterise Fe status and associations with physical performance in female New Zealand Army recruits during a 16-week basic combat training (BCT) course. Fe status indicators - Hb, serum ferritin (sFer), soluble transferrin receptor (sTfR), transferrin saturation (TS) and erythrocyte distribution width (RDW) - were assessed at the beginning (baseline) and end of BCT in seventy-six volunteers without Fe-deficiency non-anaemia (sFer 10 mg/l at baseline or end. A timed 2·4 km run followed by maximum press-ups were performed at baseline and midpoint (week 8) to assess physical performance. Changes in Fe status were investigated using paired t tests and associations between Fe status and physical performance evaluated using Pearson correlation coefficients. sFer (56·6 (sd 33·7) v. 38·4 (sd 23·8) µg/l) and TS (38·8 (sd 13·9) v. 34·4 (sd 11·5) %) decreased (P<0·001 and P=0·014, respectively), while sTfR (1·21 (sd 0·27) v. 1·39 (sd 0·35) mg/l) and RDW (12·8 (sd 0·6) v. 13·2 (sd 0·7) %) increased (P<0·001) from baseline to end. Hb (140·6 (sd 7·5) v. 142·9 (sd 7·9) g/l) increased (P=0·009) during BCT. At end, sTfR was positively (r 0·29, P=0·012) and TS inversely associated (r -0·32, P=0·005) with midpoint run time. There were no significant correlations between Fe status and press-ups. Storage and functional Fe parameters indicated a decline in Fe status in female recruits during BCT. Correlations between tissue-Fe indicators and run times suggest impaired aerobic fitness. Optimal Fe status appears paramount for enabling success in female recruits during military training.

Vitamin D3 supplementation for 8 weeks leads to improved haematological status following the consumption of an iron-fortified breakfast cereal: a double-blind randomised controlled trial in iron-deficient women.

The effect of 38 µg (1500 IU) daily vitamin D3 supplementation, consumed with an Fe-fortified breakfast cereal for 8 weeks, on haematological indicators in Fe-deficient female subjects was investigated. Fifty Fe-deficient subjects (plasma ferritin concentration <20 µg/l; mean age: 27·4 (sd 9·4) years) were randomised to consume an Fe-fortified breakfast cereal containing 9 mg of Fe daily, with either a vitamin D3 supplement or placebo. Blood samples were collected at baseline, interim (4 weeks) and post-intervention (8 weeks) for measurement of Fe and vitamin D status biomarkers. The effect of intervention was analysed using mixed-model repeated-measures ANOVA. Significant increases were observed in two main haematological indices: Hb concentration and haematocrit level from baseline to post-intervention in the vitamin D group but not in the placebo group. The increase from baseline to post-intervention in Hb concentration in the vitamin D group (135 (sd 11) to 138 (sd 10) g/l) was significantly higher compared with the placebo group (131 (sd 15) to 128 (sd 13) g/l) (P=0·037). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42·0 (sd 3·0) to 43·8 (sd 3·4) %) compared with the placebo group (41·2 (sd 4·3) to 40·7 (sd 3·6) %) (P=0·032). Despite the non-significant changes in plasma ferritin concentration, this study demonstrates that 38 µg supplemental vitamin D, consumed daily, with Fe-fortified breakfast cereal led to improvement in Hb concentration and haematocrit levels in women with low Fe stores. These findings may have therapeutic implications in the recovery of Fe status in Fe-deficient populations at a healthcare level.