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Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction
Vastmanland Cty Hosp, Dept Med, Sigtunagatan, S-72189 Vasteras, Sweden.
Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.ORCID iD: 0000-0003-2071-5866
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 187-192Article in journal (Refereed) Published
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 LTD , 2019. Vol. 124, no 3, p. 187-192
Keywords [en]
Acute myocardial infarction, biomarkers, diabetes mellitus, proteomics
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-396110DOI: 10.1080/03009734.2019.1650141ISI: 000482489400001PubMedID: 31429631OAI: oai:DiVA.org:uu-396110DiVA, id: diva2:1367122
Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved

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Dahle, NinaFall, ToveHagström, EmilLeppert, JerzyHedberg, Pär
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