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Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease

BACKGROUND: Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their el...

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Autores principales: Retnakaran, Ravi, Shah, Baiju R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635213/
https://www.ncbi.nlm.nih.gov/pubmed/36329453
http://dx.doi.org/10.1186/s12916-022-02581-0
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author Retnakaran, Ravi
Shah, Baiju R.
author_facet Retnakaran, Ravi
Shah, Baiju R.
author_sort Retnakaran, Ravi
collection PubMed
description BACKGROUND: Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. METHODS: Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM−/CVD+); those with GDM but no CVD (GDM+/CVD−); and those with neither GDM nor CVD (GDM−/CVD−). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up. RESULTS: On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM−/CVD− to GDM+/CVD− to GDM−/CVD+ to GDM+/CVD+ (all p<0.0001). At each point in time, each of the lipid and glycemic measures was significantly worse in GDM+/CVD+ compared to GDM+/CVD− (all p<0.001). Moreover, among women who did not develop CVD, all lipid and glycemic measures were significantly worse in those with previous GDM (all p<0.001 for GDM+/CVD− vs GDM−/CVD−). Mediation analyses revealed that the dominant determinants of CVD risk in women with GDM were A1c (56.0% mediation, 95%CI 47.4–67.8) and fasting glucose (47.4%, 38.8–60.8), followed by HDL (25.2%, 21.3–30.7) and triglycerides (12.1%, 9.7–15.6). Upon exclusion of those who developed diabetes during follow-up, the key determinants were HDL (40.8%), fasting glucose (37.7%), A1c (28.6%), triglycerides (21.0%), and LDL (9.9%). CONCLUSIONS: Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02581-0.
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spelling pubmed-96352132022-11-05 Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease Retnakaran, Ravi Shah, Baiju R. BMC Med Research Article BACKGROUND: Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. METHODS: Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM−/CVD+); those with GDM but no CVD (GDM+/CVD−); and those with neither GDM nor CVD (GDM−/CVD−). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up. RESULTS: On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM−/CVD− to GDM+/CVD− to GDM−/CVD+ to GDM+/CVD+ (all p<0.0001). At each point in time, each of the lipid and glycemic measures was significantly worse in GDM+/CVD+ compared to GDM+/CVD− (all p<0.001). Moreover, among women who did not develop CVD, all lipid and glycemic measures were significantly worse in those with previous GDM (all p<0.001 for GDM+/CVD− vs GDM−/CVD−). Mediation analyses revealed that the dominant determinants of CVD risk in women with GDM were A1c (56.0% mediation, 95%CI 47.4–67.8) and fasting glucose (47.4%, 38.8–60.8), followed by HDL (25.2%, 21.3–30.7) and triglycerides (12.1%, 9.7–15.6). Upon exclusion of those who developed diabetes during follow-up, the key determinants were HDL (40.8%), fasting glucose (37.7%), A1c (28.6%), triglycerides (21.0%), and LDL (9.9%). CONCLUSIONS: Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02581-0. BioMed Central 2022-11-04 /pmc/articles/PMC9635213/ /pubmed/36329453 http://dx.doi.org/10.1186/s12916-022-02581-0 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 Article
Retnakaran, Ravi
Shah, Baiju R.
Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title_full Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title_fullStr Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title_full_unstemmed Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title_short Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
title_sort mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635213/
https://www.ncbi.nlm.nih.gov/pubmed/36329453
http://dx.doi.org/10.1186/s12916-022-02581-0
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