Evidence map›Paper›PMID 40140920›Full record

ArticleCardiovascular diabetology2025

BMI-residualized data uncovers a cluster of people with type 2 diabetes and increased serum ferritin protected from cardiovascular disease.

Laura Gallardo-Nuell, Jordi Blanch, Yenny Leal, Daniel E Coral, Talita Duarte-Salles, Giuseppe N Giordano, Paul W Franks, Ewan R Pearson, Geltrude Mingrone, Carel W le Roux and 2 more

Abstract readMulticenter Study
In one paragraph

Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Laura Gallardo-Nuell *Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain.
Jordi Blanch *Grup Investigació en Salut Vascular de Girona (ISV- Girona), Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Catalunya, Spain, Catalunya, Spain.
Yenny LealDepartment of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain.
Daniel E CoralGenetic and Molecular Epidemiology Unit, Department of Clinical Science, Lund University Diabetes Centre, Lund University, Helsinborg, Sweden.
Talita Duarte-SallesFundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), IDIAP Jordi Gol, Barcelona, Catalunya, Spain.
Giuseppe N GiordanoGenetic and Molecular Epidemiology Unit, Department of Clinical Science, Lund University Diabetes Centre, Lund University, Helsinborg, Sweden.
Paul W FranksGenetic and Molecular Epidemiology Unit, Department of Clinical Science, Lund University Diabetes Centre, Lund University, Helsinborg, Sweden.
Ewan R PearsonPopulation Health and Genomics, University of Dundee, Dundee, UK.
Geltrude MingroneDepartment of Internal Medicine, Catholic University, 00168, Rome, Italy.
Carel W le RouxDiabetes Complications Research Centre, UCD Conway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
Rafael RamosGrup Investigació en Salut Vascular de Girona (ISV- Girona), Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Catalunya, Spain, Catalunya, Spain. rramos.girona.ics@gencat.cat.
José Manuel Fernández-RealDepartment of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain. jmfreal@idibgi.org.

Funding

Generalitat de Catalunya 2021 SGR 01263Innovative Medicines Initiative 2 Joint Undertaking 875534
6 · The paper itself

Abstract

backgroundUnderstanding the relationship between serum ferritin levels and cardiovascular outcomes in type 2 diabetes is crucial for improving risk stratification and guiding therapeutic interventions aimed at preventing major adverse cardiovascular events (MACE). This study aimed to identify distinct clusters of individuals with type 2 diabetes who have varying risks of MACE using a data-driven clustering approach.

methodsThis retrospective cohort study analyzed data from 49,506 individuals within a multicenter, population-based primary care registry in Catalonia, Spain. Individuals diagnosed with type 2 diabetes at age 35 or older were recruited between January 2010 and December 2021 and followed for at least 10 years. Biomarkers associated with cardiovascular risk-including serum glucose, HbA1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, serum ferritin, leukocyte, and monocyte counts-were examined. Clustering analysis was applied to identify patient subgroups, and Cox proportional hazards models were used to assess associations with cerebrovascular events, coronary events, and composite MACE.

resultsFive distinct clusters were identified, characterized by differences in serum glucose, HbA1c, lipid profiles, blood pressure, and serum ferritin levels. Individuals with discordantly high serum ferritin levels relative to their body mass index (BMI) exhibited a lower risk of adverse cardiovascular outcomes. In men, hazard ratios (HR) were 0.68 (95% confidence interval [CI]: 0.53-0.87) for cerebrovascular events, 0.65 (95% CI 0.49-0.88) for coronary events, and 0.68 (95% CI 0.56-0.83) for MACE. In women, HRs were 0.81 (95% CI 0.67-0.92) for cerebrovascular events, 0.73 (95% CI 0.57-0.95) for coronary events, and 0.79 (95% CI 0.67-0.92) for MACE.

conclusionsIndividuals with type 2 diabetes who exhibit higher-than-expected serum ferritin levels relative to their BMI may have a lower risk of cardiovascular events. These findings suggest that ferritin may play a more complex role in cardiovascular risk than previously assumed and highlight the potential for refined risk stratification strategies in type 2 diabetes management.

Indexed as

Body Mass IndexCardiovascular DiseasesDiabetes Mellitus, Type 2FerritinsAdultAgedBiomarkersCluster AnalysisFemaleGlycated HemoglobinHeart Disease Risk FactorsHumansMaleMiddle AgedPrognosisProtective FactorsBiomarkersFerritinsGlycated Hemoglobinhemoglobin A1c protein, humanBMICardiovascular diseases(s) (CVD)FerritinObesityType 2 diabetes mellitus

Identifiers

PMID40140920
PMCPMC11948634

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.