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Authors = Coby M. Laarakkers

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9 pages, 273 KiB  
Communication
Hepcidin Status in Cord Blood: Observational Data from a Tertiary Institution in Belgium
by Michael Ceulemans, Joline Van de Vel, Dorine W. Swinkels, Coby M. M. Laarakkers, Jaak Billen, Kristel Van Calsteren and Karel Allegaert
Nutrients 2023, 15(3), 546; https://doi.org/10.3390/nu15030546 - 20 Jan 2023
Cited by 2 | Viewed by 2229
Abstract
The hormone hepcidin plays an important role in intestinal iron absorption and cellular release. Cord blood hepcidin values reflect fetal hepcidin status, at least at the time of delivery, but are not available for the Belgian population. Therefore, we aimed (1) to provide [...] Read more.
The hormone hepcidin plays an important role in intestinal iron absorption and cellular release. Cord blood hepcidin values reflect fetal hepcidin status, at least at the time of delivery, but are not available for the Belgian population. Therefore, we aimed (1) to provide the first data on cord blood hepcidin levels in a Belgian cohort and (2) to determine variables associated with cord blood hepcidin concentrations. A cross-sectional, observational study was performed at the University Hospital Leuven, Belgium. Cord blood samples were analyzed using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry. Descriptive statistics, Spearman correlation tests, and Mann–Whitney U tests were performed. In total, 61 nonhemolyzed cord blood samples were analyzed. The median hepcidin level was 17.6 μg/L (IQR: 18.1; min-max: 3.9–54.7). A moderate correlation was observed between cord blood hepcidin and cord blood ferritin (r = 0.493) and hemoglobin (r = −0.342). Cord blood hepcidin was also associated with mode of delivery (p = 0.01), with higher hepcidin levels for vaginal deliveries. Nonetheless, larger studies are needed to provide more evidence on the actual clinical value and benefit of cord blood hepcidin measurements. Full article
(This article belongs to the Special Issue Physiology and Pathophysiology of Iron Metabolism)
16 pages, 966 KiB  
Article
Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
by Hilde van der Staaij, Albertine E. Donker, Dirk L. Bakkeren, Jan M. J. I. Salemans, Lisette A. A. Mignot-Evers, Marlies Y. Bongers, Jeanne P. Dieleman, Tessel E. Galesloot, Coby M. Laarakkers, Siem M. Klaver and Dorine W. Swinkels
Int. J. Mol. Sci. 2022, 23(3), 1917; https://doi.org/10.3390/ijms23031917 - 8 Feb 2022
Cited by 9 | Viewed by 6043
Abstract
Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation [...] Read more.
Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4–1.1%/nM) and 16.7%/nM (IQR, 12.0–24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84–100% and 91–100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population. Full article
(This article belongs to the Special Issue New Advances in Iron Metabolism, Ferritin and Hepcidin Research)
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13 pages, 1188 KiB  
Article
Menopause Delays the Typical Recovery of Pre-Exercise Hepcidin Levels after High-Intensity Interval Running Exercise in Endurance-Trained Women
by Víctor M. Alfaro-Magallanes, Pedro J. Benito, Beatriz Rael, Laura Barba-Moreno, Nuria Romero-Parra, Rocío Cupeiro, Dorine W. Swinkels, Coby M. Laarakkers, Ana B. Peinado and on behalf of the IronFEMME Study Group
Nutrients 2020, 12(12), 3866; https://doi.org/10.3390/nu12123866 - 17 Dec 2020
Cited by 3 | Viewed by 4170
Abstract
Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. [...] Read more.
Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. As this fact has not been studied in postmenopausal women, this study investigated the hepcidin response to running exercise in this population. Thirteen endurance-trained postmenopausal women (age: 51.5 ± 3.89 years; height: 161.8 ± 4.9 cm; body mass: 55.9 ± 3.6 kg; body fat: 24.7 ± 4.2%; peak oxygen consumption: 42.4 ± 4.0 mL·min−1·kg−1) performed a high-intensity interval running protocol, which consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed with 90-second recovery. Blood samples were collected pre-exercise, 0, 3, and 24 hours post-exercise. As expected, hepcidin exhibited higher values at 3 hours post-exercise (3.69 ± 3.38 nmol/L), but also at 24 hours post-exercise (3.25 ± 3.61 nmol/L), in comparison with pre-exercise (1.77 ± 1.74 nmol/L; p = 0.023 and p = 0.020, respectively) and 0 hour post-exercise (2.05 ± 2.00 nmol/L; p = 0.021 and p = 0.032, respectively) concentrations. These differences were preceded by a significant increment of interleukin-6 at 0 hour post-exercise (3.41 ± 1.60 pg/mL) compared to pre-exercise (1.65 ± 0.48 pg/m, p = 0.003), 3 hours (1.50 ± 0.00 pg/mL, p = 0.002) and 24 hours post-exercise (1.52 ± 0.07 pg/mL, p = 0.001). Hepcidin peaked at 3 hours post-exercise as the literature described for premenopausal women but does not seem to be fully recovered to pre-exercise levels within 24 hours post-exercise, as it would be expected. This suggests a slower recovery of basal hepcidin levels in postmenopausal women, suggesting interesting applications in order to modify iron homeostasis as appropriate, such as the prevention of iron accumulation or proper timing of iron supplementation. Full article
(This article belongs to the Special Issue Health Benefits of Particular Exercise and Nutrition)
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13 pages, 1561 KiB  
Concept Paper
Unraveling Hepcidin Plasma Protein Binding: Evidence from Peritoneal Equilibration Testing
by Laura E. Diepeveen, Coby M. Laarakkers, Hilde P.E. Peters, Antonius E. van Herwaarden, Hans Groenewoud, Joanna IntHout, Jack F. Wetzels, Rachel P.L. van Swelm and Dorine W. Swinkels
Pharmaceuticals 2019, 12(3), 123; https://doi.org/10.3390/ph12030123 - 23 Aug 2019
Cited by 10 | Viewed by 4223
Abstract
Peptide hormone hepcidin regulates systemic iron metabolism and has been described to be partially bound to α2-macroglobulin and albumin in blood. However, the reported degree of hepcidin protein binding varies between <3% and ≈89%. Since protein-binding may influence hormone function and quantification, better [...] Read more.
Peptide hormone hepcidin regulates systemic iron metabolism and has been described to be partially bound to α2-macroglobulin and albumin in blood. However, the reported degree of hepcidin protein binding varies between <3% and ≈89%. Since protein-binding may influence hormone function and quantification, better insight into the degree of hepcidin protein binding is essential to fully understand the biological behavior of hepcidin and interpretation of its measurement in patients. Here, we used peritoneal dialysis to assess human hepcidin protein binding in a functional human setting for the first time. We measured freely circulating solutes in blood and peritoneal fluid of 14 patients with end-stage renal disease undergoing a peritoneal equilibration test to establish a curve describing the relation between molecular weight and peritoneal clearance. Calculated binding percentages of total cortisol and testosterone confirmed our model. The protein-bound fraction of hepcidin was calculated to be 40% (±23%). We, therefore, conclude that a substantial proportion of hepcidin is freely circulating. Although a large inter-individual variation in hepcidin clearance, besides patient-specific peritoneal transport characteristics, may have affected the accuracy of the determined binding percentage, we describe an important step towards unraveling human hepcidin plasma protein binding in vivo including the caveats that need further research. Full article
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
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