Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial.
Aged
Biomarkers
/ blood
Blood Proteins
/ analysis
Diabetes Mellitus
/ blood
Diabetic Cardiomyopathies
/ blood
Female
Heart Failure
/ blood
Humans
Male
Mineralocorticoid Receptor Antagonists
/ therapeutic use
Predictive Value of Tests
Prospective Studies
Proteome
Proteomics
Risk Assessment
Risk Factors
Spironolactone
/ therapeutic use
Time Factors
Treatment Outcome
Biomarker
Diabetes
Fibrosis
Heart failure
Spironolactone
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
09 08 2021
09 08 2021
Historique:
received:
03
06
2021
accepted:
29
07
2021
entrez:
10
8
2021
pubmed:
11
8
2021
medline:
4
1
2022
Statut:
epublish
Résumé
Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The "Heart OMics in AGEing" (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.
Sections du résumé
BACKGROUND
Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The "Heart OMics in AGEing" (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial.
METHODS
Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes.
RESULTS
Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05).
CONCLUSIONS
Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.
Identifiants
pubmed: 34372849
doi: 10.1186/s12933-021-01357-9
pii: 10.1186/s12933-021-01357-9
pmc: PMC8351439
doi:
Substances chimiques
Biomarkers
0
Blood Proteins
0
Mineralocorticoid Receptor Antagonists
0
Proteome
0
Spironolactone
27O7W4T232
Banques de données
ClinicalTrials.gov
['NCT02556450']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
163Informations de copyright
© 2021. The Author(s).
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