, Volume 63, Issue 1, pp 44–51 | Cite as

Cause-specific risk of major adverse cardiovascular outcomes and hypoglycemic in patients with type 2 diabetes: a multicenter prospective cohort study

  • Bao Sun
  • Fazhong He
  • Lei Sun
  • Jiecan Zhou
  • Jiayi Shen
  • Jing Xu
  • Bin Wu
  • Rong Liu
  • Xingyu Wang
  • Heng Xu
  • Xiaoping Chen
  • Honghao Zhou
  • Zhaoqian Liu
  • Wei ZhangEmail author
Original Article



Glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) was identified to account for the risk of cardiovascular diseases in type 2 diabetic patients, but no study evaluated the risk based on both HbA1c and FPG levels. We described the risk of major adverse cardiovascular events (MACE) and hypoglycemic in type 2 diabetic patients according to both HbA1c and FPG levels.


With the usage of databases of Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), 1815 patients from 61 centers in China was identified and grouped according to the criterion value of HbA1c and FPG: Good glycemic control (HbA1c < 6.5%, FPG < 6.1 mmol/L); Insufficient glycemic control (HbA1c < 6.5%, FPG ≥ 6.1 mmol/L or HbA1c ≥ 6.5%, FPG < 6.1 mmol/L); Poor glycemic control (HbA1c ≥ 6.5%, FPG ≥ 6.1 mmol/L). Time-varying multivariable Cox proportional hazards models were employed.


Average age was 64.8 ± 5.8 years, with a median of 4.8 years of follow-up. Overall, the incidence rates of MACE were 20.6 per 1000-person-years in Good glycemic control compared with 45.9 per 1000-person-years in Insufficient glycemic control (adjusted hazard ratio (aHR): 1.99; 95% CI 1.11–3.56; p = 0.02) and 54.7 per 1000-person-years in Poor glycemic control (aHR: 2.46; 95% CI 1.38–4.40; p = 0.002), respectively. The risk of hypoglycemic was highest in Insufficient glycemic control; 67.3 per 1000-person-years compared with 46.3 per 1000-person-years in Good glycemic control (aHR: 1.62; 95% CI 1.03–2.56; p = 0.04). Apart from this, we also observed that both MACE (aHR:1.41; 95% CI 1.13–1.77; p = 0.003) and hypoglycemic episodes (aHR: 1.82; 95% CI 1.48–2.24; p < 0.001) were sufficiently more frequent in the insulin-exposed group than the non-exposed group. In a post-hoc analysis, the risk of MACE (aHR:1.43; 95% CI 1.09–1.86; p = 0.01) and hypoglycemic (aHR: 1.99; 95% CI 1.46–2.69; p < 0.001) were more pronounced in Insufficient glycemic control with insulin exposure.


We observed a significant association of cause-specific risk of MACE and hypoglycemic with Insufficient glycemic control, particularly with insulin exposure.


Type 2 diabetes Major adverse cardiovascular events Good glycemic control Insufficient glycemic control Poor glycemic control 



Glycated hemoglobin A1c


fasting plasma glucose


major adverse cardiovascular events


Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation


adjusted hazard ratio


Interquartile range


body mass index


Action to Control Cardiovascular Risk in Diabetes


Veterans Affairs Diabetes Trail.



We acknowledge the contributions of ADVANCE group at 61 centers in China. We also thank all patients and participants who have contributed to the register.


This work was funded by grants from National Key Research and Development Program (No. 2016YFC0905000), National Natural Science Foundation of China (No 81522048, 81573511) and the Innovation Driven Project of Central South University (No 2016CX024).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the local ethics committee and was in accordance with the 1964 Helsinki declaration and its later amendments.

Informed consent

All patients provide written informed consent.

Supplementary material

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Supplementary Figure
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Supplementary Table 1
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Supplementary Figure legend


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Bao Sun
    • 1
    • 2
  • Fazhong He
    • 1
    • 2
  • Lei Sun
    • 3
  • Jiecan Zhou
    • 1
    • 2
  • Jiayi Shen
    • 1
    • 2
  • Jing Xu
    • 1
    • 2
  • Bin Wu
    • 1
    • 2
  • Rong Liu
    • 1
    • 2
  • Xingyu Wang
    • 4
  • Heng Xu
    • 5
  • Xiaoping Chen
    • 1
    • 2
  • Honghao Zhou
    • 1
    • 2
  • Zhaoqian Liu
    • 1
    • 2
  • Wei Zhang
    • 1
    • 2
    Email author
  1. 1.Department of Clinical Pharmacology, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Institute of Clinical Pharmacology, Central South UniversityHunan Key Laboratory of pharmacogeneticsChangshaChina
  3. 3.Data Analysis Technology Lab, School of Mathematics and StatisticsHenan UniversityKaifengChina
  4. 4.Beijing Hypertension League InstituteBeijingChina
  5. 5.Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China HospitalSichuan UniversityChengduChina

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