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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

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Abbreviations

HbA1c :

Glycated hemoglobin A1c

FPG:

fasting plasma glucose

MACE:

major adverse cardiovascular events

ADVANCE:

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

aHR:

adjusted hazard ratio

IQR:

Interquartile range

BMI:

body mass index

ACCORD:

Action to Control Cardiovascular Risk in Diabetes

VADT:

Veterans Affairs Diabetes Trail.

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Acknowledgements

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.

Funding

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).

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, China

    Bao Sun, Fazhong He, Jiecan Zhou, Jiayi Shen, Jing Xu, Bin Wu, Rong Liu, Xiaoping Chen, Honghao Zhou, Zhaoqian Liu & Wei Zhang

  2. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of pharmacogenetics, Changsha, 410078, China

    Bao Sun, Fazhong He, Jiecan Zhou, Jiayi Shen, Jing Xu, Bin Wu, Rong Liu, Xiaoping Chen, Honghao Zhou, Zhaoqian Liu & Wei Zhang

  3. Data Analysis Technology Lab, School of Mathematics and Statistics, Henan University, Kaifeng, 475004, China

    Lei Sun

  4. Beijing Hypertension League Institute, 24 Shijingshan Road, Beijing, 100043, China

    Xingyu Wang

  5. Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

    Heng Xu

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  1. Bao Sun
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  2. Fazhong He
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  3. Lei Sun
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  12. Honghao Zhou
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  14. Wei Zhang
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Correspondence to Wei Zhang.

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

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Sun, B., He, F., Sun, L. et al. Cause-specific risk of major adverse cardiovascular outcomes and hypoglycemic in patients with type 2 diabetes: a multicenter prospective cohort study. Endocrine 63, 44–51 (2019). https://doi.org/10.1007/s12020-018-1715-0

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