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HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control

BACKGROUND: Reduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs. METHODS: I...

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Autores principales: Denimal, Damien, Monier, Serge, Simoneau, Isabelle, Duvillard, Laurence, Vergès, Bruno, Bouillet, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375300/
https://www.ncbi.nlm.nih.gov/pubmed/35962339
http://dx.doi.org/10.1186/s12933-022-01591-9
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author Denimal, Damien
Monier, Serge
Simoneau, Isabelle
Duvillard, Laurence
Vergès, Bruno
Bouillet, Benjamin
author_facet Denimal, Damien
Monier, Serge
Simoneau, Isabelle
Duvillard, Laurence
Vergès, Bruno
Bouillet, Benjamin
author_sort Denimal, Damien
collection PubMed
description BACKGROUND: Reduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs. METHODS: In this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate. RESULTS: HbA(1c) decreased from 11.4% [10.2–12.9] (median [1st–3rd quartiles]) at baseline to 8.1% [6.6–9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = −0.411, P = 0.034), even after adjustment for the change in HbA(1c) (β = −0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively. CONCLUSIONS: The improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients. Trial registration: NCT02816099 ClinicalTrials.gov.
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spelling pubmed-93753002022-08-14 HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control Denimal, Damien Monier, Serge Simoneau, Isabelle Duvillard, Laurence Vergès, Bruno Bouillet, Benjamin Cardiovasc Diabetol Research BACKGROUND: Reduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs. METHODS: In this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate. RESULTS: HbA(1c) decreased from 11.4% [10.2–12.9] (median [1st–3rd quartiles]) at baseline to 8.1% [6.6–9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = −0.411, P = 0.034), even after adjustment for the change in HbA(1c) (β = −0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively. CONCLUSIONS: The improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients. Trial registration: NCT02816099 ClinicalTrials.gov. BioMed Central 2022-08-12 /pmc/articles/PMC9375300/ /pubmed/35962339 http://dx.doi.org/10.1186/s12933-022-01591-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Denimal, Damien
Monier, Serge
Simoneau, Isabelle
Duvillard, Laurence
Vergès, Bruno
Bouillet, Benjamin
HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title_full HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title_fullStr HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title_full_unstemmed HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title_short HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control
title_sort hdl functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased hdl carbamylation after improvement of glycemic control
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375300/
https://www.ncbi.nlm.nih.gov/pubmed/35962339
http://dx.doi.org/10.1186/s12933-022-01591-9
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