Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.

<h4>Background</h4>Harmful effects of long-term HbA1c and fasting plasma glucose (FPG) variability on cardiovascular diseases (CVD) have not been causally examined. We employed a parametric g-formula to estimate the causal effect of HbA1C and fasting plasma glucose (FPG) variability on C...

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Main Authors: Khadije Maajani, Ensieh Nasli-Esfahani, Noushin Fahimfar, Ali Sheidaei, Mohammad Ali Mansournia, Kamran Yazdani
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0319975
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author Khadije Maajani
Ensieh Nasli-Esfahani
Noushin Fahimfar
Ali Sheidaei
Mohammad Ali Mansournia
Kamran Yazdani
author_facet Khadije Maajani
Ensieh Nasli-Esfahani
Noushin Fahimfar
Ali Sheidaei
Mohammad Ali Mansournia
Kamran Yazdani
author_sort Khadije Maajani
collection DOAJ
description <h4>Background</h4>Harmful effects of long-term HbA1c and fasting plasma glucose (FPG) variability on cardiovascular diseases (CVD) have not been causally examined. We employed a parametric g-formula to estimate the causal effect of HbA1C and fasting plasma glucose (FPG) variability on CVD.<h4>Methods</h4>This retrospective cohort study was conducted on 2078 patients with type 2 diabetes who were free of CVD and aged >18 years at the entrance to the clinic (2017-2022), with at least three HbA1c and FPG measurements. Variability was calculated using standard deviation (SD), and coefficient of variation (CV). We used the parametric g-formula to estimate the 5-year risk, risk ratio, and risk difference of CVD under different deciles of HbA1c-SD/CV, FPG-SD/CV, HbA1C levels (≤5%, 5 to ≤7%, and >7), and joint exposure to different deciles of HbA1c-SD and HbA1c values, adjusted for time-varying confounders that are affected by prior exposure.<h4>Results</h4>The observed and simulated 5-year risk of CVD under no intervention were 11.6% (95% CI: 10.3, 13.1) and 11.03% (95% CI: 10.2, 12.6) for HbA1C-SD model. The estimated 5-year risk of CVD was increased from the 8.01% (95% CI: 7.5, 10.1%) in the first decile to 15.2% (95% CI: 14.1, 17.7%) in the tenth decile of HbA1c-SD. The results for FPG-SD were similar. Within the stable level of HbA1c (5 to ≤7%) the risk ratio increased from 1.37 (95% CI: 1.19, 1.48) in the first decile to 2.76 (95% CI: 2.06, 3.09) in the tenth decile of HbA1c-SD. Under a joint intervention of HbA1c <5% and the first decile of HbA1c-SD, CVD risk decreased by 6.4% (95%CI: 4.9, 7.3%) compared to the natural course.<h4>Conclusions</h4>Even within a stable HbA1c level, long-term glycemic variability may be a strong predictor of CVD.
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spelling doaj-art-2d0490d15ef24dcd8ba8212b94a40d9d2025-08-20T02:23:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e031997510.1371/journal.pone.0319975Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.Khadije MaajaniEnsieh Nasli-EsfahaniNoushin FahimfarAli SheidaeiMohammad Ali MansourniaKamran Yazdani<h4>Background</h4>Harmful effects of long-term HbA1c and fasting plasma glucose (FPG) variability on cardiovascular diseases (CVD) have not been causally examined. We employed a parametric g-formula to estimate the causal effect of HbA1C and fasting plasma glucose (FPG) variability on CVD.<h4>Methods</h4>This retrospective cohort study was conducted on 2078 patients with type 2 diabetes who were free of CVD and aged >18 years at the entrance to the clinic (2017-2022), with at least three HbA1c and FPG measurements. Variability was calculated using standard deviation (SD), and coefficient of variation (CV). We used the parametric g-formula to estimate the 5-year risk, risk ratio, and risk difference of CVD under different deciles of HbA1c-SD/CV, FPG-SD/CV, HbA1C levels (≤5%, 5 to ≤7%, and >7), and joint exposure to different deciles of HbA1c-SD and HbA1c values, adjusted for time-varying confounders that are affected by prior exposure.<h4>Results</h4>The observed and simulated 5-year risk of CVD under no intervention were 11.6% (95% CI: 10.3, 13.1) and 11.03% (95% CI: 10.2, 12.6) for HbA1C-SD model. The estimated 5-year risk of CVD was increased from the 8.01% (95% CI: 7.5, 10.1%) in the first decile to 15.2% (95% CI: 14.1, 17.7%) in the tenth decile of HbA1c-SD. The results for FPG-SD were similar. Within the stable level of HbA1c (5 to ≤7%) the risk ratio increased from 1.37 (95% CI: 1.19, 1.48) in the first decile to 2.76 (95% CI: 2.06, 3.09) in the tenth decile of HbA1c-SD. Under a joint intervention of HbA1c <5% and the first decile of HbA1c-SD, CVD risk decreased by 6.4% (95%CI: 4.9, 7.3%) compared to the natural course.<h4>Conclusions</h4>Even within a stable HbA1c level, long-term glycemic variability may be a strong predictor of CVD.https://doi.org/10.1371/journal.pone.0319975
spellingShingle Khadije Maajani
Ensieh Nasli-Esfahani
Noushin Fahimfar
Ali Sheidaei
Mohammad Ali Mansournia
Kamran Yazdani
Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
PLoS ONE
title Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
title_full Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
title_fullStr Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
title_full_unstemmed Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
title_short Long-term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients: Effect of hypothetical interventions using parametric g-formula in a population-based historical cohort study.
title_sort long term glycemic variability and the risk of cardiovascular diseases in type 2 diabetic patients effect of hypothetical interventions using parametric g formula in a population based historical cohort study
url https://doi.org/10.1371/journal.pone.0319975
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