Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes Original paper

What was studied?

In this cross-sectional IRODIAB analysis, hepcidin in pediatric type 1 diabetes was evaluated as a potential biomarker to distinguish functional iron deficiency (FID) from absolute iron deficiency (AID) and normal iron status in children with type 1 diabetes (T1D). The authors hypothesized that chronic low-grade inflammation in T1D would upregulate hepcidin and thereby contribute to FID; they therefore measured serum hepcidin (mass-spectrometry) alongside multiple iron indices and post-hoc alternative FID definitions to test whether a single hepcidin value could meaningfully classify iron status phenotypes in routine care.

Who was studied?

Participants were 215 Dutch children and adolescents with established T1D (median age 13.7 years) enrolled from two pediatric centers, with data collected during follow-up visits in 2015–2016. Eligibility required age 1–19 years and T1D duration ≥1 year; key exclusions aimed to reduce confounding by acute inflammation or recent iron manipulation (recent infection, recent iron supplementation, transfusion, and other major comorbidities). Children with hsCRP ≥10 mg/L were not included in analyses, strengthening inference toward chronic rather than acute inflammatory effects on hepcidin.

Most important findings

Across the cohort, iron status phenotypes were common: 47.4% had normal iron status, 5.1% had AID, and 47.0% had FID by the main definition (ZnPP/H and/or RDW abnormalities without low ferritin). Hepcidin behaved as expected for depleted iron stores—AID showed very low hepcidin—yet it failed to separate FID from normal iron status: median hepcidin was 1.8 nmol/L in normal iron status versus 1.6 nmol/L in FID (not significantly different), while AID was 0.4 nmol/L and significantly lower than both groups. Importantly for a microbiome signatures database, this article did not measure gut microbiome composition, microbial metabolites, or taxa-level associations, so no organism-specific signature can be extracted; the relevance is mechanistic (iron restriction and inflammation biology) rather than microbial mapping. The authors argue that single-timepoint hepcidin may be “normalized” by competing stimuli and timing mismatches among biomarkers (hepcidin is rapidly responsive, while RDW/ZnPP/H reflect longer erythrocyte time windows), and that non-fasting sampling could further blur iron–hepcidin relationships.

Key implications

Clinically, hepcidin in pediatric type 1 diabetes should not be used as a standalone, single-draw test to diagnose FID in youth with T1D, because it does not reliably differ from values seen with normal iron status, despite FID being prevalent; in contrast, very low hepcidin supports true iron store depletion (AID) when present. For translational microbiome thinking, the takeaway is negative but useful: if future microbiome studies in T1D use hepcidin as a proxy for “inflammation-driven iron sequestration,” single measurements may misclassify host iron ecology, weakening any downstream attempt to link taxa to iron-restricted states; longitudinal hepcidin plus iron indices would likely produce cleaner host-phenotype labels for any microbiome–iron signature work.

Citation

Vreugdenhil M, Akkermans MD, van Swelm RPL, et al. Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes. Pediatr Hematol Oncol. 2021;38(2):108-123. doi:10.1080/08880018.2020.1820650