Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study
Abstract Background Prediabetes and insulin resistance are linked to the presence and progression of coronary artery calcification, but their prognostic significance in individuals with moderate-to-severe coronary artery calcification (MSCAC) remains unclear. The triglyceride–glucose (TyG) index, a...
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BMC
2025-07-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02807-4 |
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| author | Enmin Xie Huimin Cai Zixiang Ye Min Yang Lei Feng Chenggang Zhu Jia Li Kefei Dou |
| author_facet | Enmin Xie Huimin Cai Zixiang Ye Min Yang Lei Feng Chenggang Zhu Jia Li Kefei Dou |
| author_sort | Enmin Xie |
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| description | Abstract Background Prediabetes and insulin resistance are linked to the presence and progression of coronary artery calcification, but their prognostic significance in individuals with moderate-to-severe coronary artery calcification (MSCAC) remains unclear. The triglyceride–glucose (TyG) index, a validated surrogate marker of insulin resistance and a reliable predictor of cardiovascular outcomes, has not been thoroughly investigated for its role in risk stratification in patients with MSCAC. This study sought to evaluate the prognostic value of different prediabetes definitions and to determine whether the TyG index enhances risk stratification in this population. Methods This prospective cohort study consecutively enrolled 4195 patients with angiography-detected MSCAC. Prediabetes was defined using two criteria: the American Diabetes Association (ADA) criteria (fasting plasma glucose [FPG] 5.6–6.9 mmol/L and/or hemoglobin A1c [HbA1c] 5.7–6.4%), and the World Health Organization (WHO)/International Expert Committee (IEC) criteria (FPG 6.1–6.9 mmol/L and/or HbA1c 6.0–6.4%). The primary outcome was the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. Results The prevalence of ADA-defined prediabetes was 36.6%, nearly twice that of WHO/IEC-defined prediabetes (17.9%). Over a median follow-up of 3.1 years, WHO/IEC-defined prediabetes was significantly associated with an increased risk of MACE compared to normoglycemia (adjusted hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.07–2.99), while ADA-defined prediabetes was not. Patients in the highest TyG index tertile had a significantly higher MACE risk than those in the lowest tertile (adjusted HR 2.25, 95% CI 1.30–3.90). Restricted cubic spline analysis demonstrated a positive linear association between the TyG index and MACE risk (P for nonlinearity > 0.05). Notably, individuals with both WHO/IEC-defined prediabetes and a high TyG index had an even higher MACE risk (adjusted HR 2.43, 95% CI 1.12–5.32), whereas those with prediabetes and a low TyG index did not demonstrate a comparable increase (adjusted HR 1.60, 95% CI 0.90–2.85). Incorporating both WHO/IEC-defined glycemic status and the TyG index into the baseline risk model significantly improved its predictive accuracy compared to including either marker alone, as indicated by enhancements in the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. These findings were consistent in subgroup analyses and sensitivity analyses. Conclusion This study highlights the prognostic value of WHO/IEC-defined prediabetes and the TyG index in identifying high-risk individuals among patients with MSCAC. Integrating these measures into clinical risk assessment may enhance prognostic accuracy and inform more targeted prevention strategies. Graphical abstract |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-88feeb7116bc44d084d8db9b69f36dae2025-08-20T04:01:24ZengBMCCardiovascular Diabetology1475-28402025-07-0124111410.1186/s12933-025-02807-4Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort studyEnmin Xie0Huimin Cai1Zixiang Ye2Min Yang3Lei Feng4Chenggang Zhu5Jia Li6Kefei Dou7Cardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInnovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric DiseasesDepartment of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCardiometabolic Medicine Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Prediabetes and insulin resistance are linked to the presence and progression of coronary artery calcification, but their prognostic significance in individuals with moderate-to-severe coronary artery calcification (MSCAC) remains unclear. The triglyceride–glucose (TyG) index, a validated surrogate marker of insulin resistance and a reliable predictor of cardiovascular outcomes, has not been thoroughly investigated for its role in risk stratification in patients with MSCAC. This study sought to evaluate the prognostic value of different prediabetes definitions and to determine whether the TyG index enhances risk stratification in this population. Methods This prospective cohort study consecutively enrolled 4195 patients with angiography-detected MSCAC. Prediabetes was defined using two criteria: the American Diabetes Association (ADA) criteria (fasting plasma glucose [FPG] 5.6–6.9 mmol/L and/or hemoglobin A1c [HbA1c] 5.7–6.4%), and the World Health Organization (WHO)/International Expert Committee (IEC) criteria (FPG 6.1–6.9 mmol/L and/or HbA1c 6.0–6.4%). The primary outcome was the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. Results The prevalence of ADA-defined prediabetes was 36.6%, nearly twice that of WHO/IEC-defined prediabetes (17.9%). Over a median follow-up of 3.1 years, WHO/IEC-defined prediabetes was significantly associated with an increased risk of MACE compared to normoglycemia (adjusted hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.07–2.99), while ADA-defined prediabetes was not. Patients in the highest TyG index tertile had a significantly higher MACE risk than those in the lowest tertile (adjusted HR 2.25, 95% CI 1.30–3.90). Restricted cubic spline analysis demonstrated a positive linear association between the TyG index and MACE risk (P for nonlinearity > 0.05). Notably, individuals with both WHO/IEC-defined prediabetes and a high TyG index had an even higher MACE risk (adjusted HR 2.43, 95% CI 1.12–5.32), whereas those with prediabetes and a low TyG index did not demonstrate a comparable increase (adjusted HR 1.60, 95% CI 0.90–2.85). Incorporating both WHO/IEC-defined glycemic status and the TyG index into the baseline risk model significantly improved its predictive accuracy compared to including either marker alone, as indicated by enhancements in the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. These findings were consistent in subgroup analyses and sensitivity analyses. Conclusion This study highlights the prognostic value of WHO/IEC-defined prediabetes and the TyG index in identifying high-risk individuals among patients with MSCAC. Integrating these measures into clinical risk assessment may enhance prognostic accuracy and inform more targeted prevention strategies. Graphical abstracthttps://doi.org/10.1186/s12933-025-02807-4Coronary artery calcificationInsulin resistancePrediabetesPrognosisTriglyceride-glucose index |
| spellingShingle | Enmin Xie Huimin Cai Zixiang Ye Min Yang Lei Feng Chenggang Zhu Jia Li Kefei Dou Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study Cardiovascular Diabetology Coronary artery calcification Insulin resistance Prediabetes Prognosis Triglyceride-glucose index |
| title | Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study |
| title_full | Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study |
| title_fullStr | Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study |
| title_full_unstemmed | Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study |
| title_short | Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study |
| title_sort | association of prediabetes and insulin resistance on prognosis of patients with moderate to severe coronary artery calcification a prospective cohort study |
| topic | Coronary artery calcification Insulin resistance Prediabetes Prognosis Triglyceride-glucose index |
| url | https://doi.org/10.1186/s12933-025-02807-4 |
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