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Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction
Department of Medicine, Västmanland County Hospital, Västerås, Sweden.
Örebro University, School of Medical Sciences. Department of Cardiology.ORCID iD: 0000-0002-9821-0510
Centre for Clinical Research, Uppsala University, Falun, Dalarna, Sweden.
Department of Medical Sciences, Molecular Epidemiology and SciLife Laboratory, Uppsala University, Uppsala, Sweden.
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identification of patients at highest risk for diabetes.

Materials and methods: In this prospective cohort, 626 patients without known diabetes underwent oral glucose tolerance testing (OGTT) during admission for MI. Proximity extension assay was used to measure 81 biomarkers. Multivariable logistic regression, adjusting for risk factors, was used to evaluate the association of biomarkers with dysglycaemia. Subsequently, lasso regression was performed in a 2/3 training set to identify proteomic biomarkers with prognostic value for dysglycaemia, when added to risk factors, fasting plasma glucose, and glycated haemoglobin A1c. Determination of discriminatory ability was performed in a 1/3 test set.

Results: In total, 401/626 patients (64.1%) met the criteria for dysglycaemia. Using multivariable logistic regression, cathepsin D had the strongest association with dysglycaemia. Lasso regression selected seven markers, including cathepsin D, that improved prediction of dysglycaemia (area under the receiver operator curve [AUC] 0.848 increased to 0.863). In patients with normal fasting plasma glucose, only cathepsin D was selected (AUC 0.699 increased to 0.704).

Conclusions: Newly detected dysglycaemia, including manifest diabetes, is common in patients with acute MI. Cathepsin D improved the prediction of dysglycaemia, which may be helpful in the a priori risk determination of diabetes as a motivation for confirmatory OGTT.

Place, publisher, year, edition, pages
Taylor & Francis, 2019.
Keywords [en]
Acute myocardial infarction, biomarkers, diabetes mellitus, proteomics
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:oru:diva-76184DOI: 10.1080/03009734.2019.1650141ISI: 000482489400001PubMedID: 31429631OAI: oai:DiVA.org:oru-76184DiVA, id: diva2:1349845
Note

Funding Agency:

Regional Research Council Uppsala-Örebro, Sweden  RFR-743621

Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-09-10Bibliographically approved

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Calais, Fredrik

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