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Prognostic impact of visit-to-visit glycemic variability on the risks of major adverse cardiovascular outcomes and hypoglycemia in patients with different glycemic control and type 2 diabetes

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Abstract

Purpose

The prognostic impact of visit-to-visit glycemic variability on clinical outcomes in patients with different glycemic control and type 2 diabetes remains obscure. We investigated glucose variability and clinical outcomes for patients in the groups of Good glycemic control (GC), Insufficient glycemic control (IC), and Poor glycemic control (PC) in a prospective cohort study.

Methods

By using data from Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), 930 patients were enrolled from 61 centers in China and grouped into GC, IC, and PC according to their glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG). Visit-to-visit glycemic variability was defined using the coefficient of variation (CV) of five measurements of HbA1c and FPG taken 3–24 months after treatment. Multivariable Cox proportional hazards models were employed to estimate adjusted hazard ratio (aHR).

Results

Among 930 patients in the intensive glucose control, 82, 538, and 310 patients were assigned to GC, IC, and PC, respectively. During the median of 4.8 years of follow-up, 322 patients were observed hypoglycemia and 244 patients experienced major adverse cardiovascular events (MACE). The CV of HbA1c and FPG was significantly lower for GC (6.0 ± 3.8, 11.2 ± 6.2) than IC (8.3 ± 5.6, 17.9 ± 10.6) and PC (9.5 ± 6.3, 19.3 ± 10.8). High glycemic variability was associated with a greater risk of MACE (aHR: 2.21; 95% confidence interval (CI): 1.61–3.03; p < 0.001) and hypoglycemia (aHR: 1.36; 95% CI: 1.04–1.79; p = 0.025) than low glycemic variability in total patients. The consistent trend was also found in subgroups of GC, IC, and PC.

Conclusions

This prospective cohort study showed that glycemic variability was significantly lower for GC than IC and PC. Furthermore, glycemic variability was associated with the risk of MACE and hypoglycemia in total patients and subgroups of different glycemic control.

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Abbreviations

GC:

Good glycemic control

IC:

Insufficient glycemic control

PC:

Poor glycemic control

ADVANCE:

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

HbA1c :

Glycated hemoglobin A1c

FPG:

Fasting plasma glucose

CV:

Coefficient of variation

aHR:

Adjusted hazard ratio

MACE:

Major adverse cardiovascular events

SD:

Standard deviations

BMI:

Body mass index

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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 research was funded by grants from National Key Research and Development Program (No. 2016YFC0905000), National Natural Science Foundation of China (Nos. 81522048, 81573511, and 81874329) and the Innovation Driven Project of Central South University (No. 2016CX024).

Author information

Author notes

  1. These authors jointly supervised this work: Bao Sun, Fazhong He

Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 410078, Changsha, People’s Republic of China

    Bao Sun, Fazhong He, Yongchao Gao, Jiecan Zhou, Rong Liu, Xiaoping Chen, Honghao Zhou, Zhaoqian Liu & Wei Zhang

  2. Hunan Key Laboratory of Pharmacogenetics, Department of Clinical Pharmacology, Institute of Clinical Pharmacology, Central South University, 410078, Changsha, People’s Republic of China

    Bao Sun, Fazhong He, Yongchao Gao, Jiecan Zhou, Rong Liu, Xiaoping Chen, Honghao Zhou, Zhaoqian Liu & Wei Zhang

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

    Lei Sun

  4. Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Heng Xu

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  1. Bao Sun
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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 Declaration of Helsinki and its later amendmentsmed consent.

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These authors contributed equally: Bao Sun, Fazhong He

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12020_2019_1893_MOESM1_ESM.docx

Supplementary table (We found some mistakes in the Supplementary Table 1. So we validated the original data and replaced it by a new Supplementary Table 1 in the attachments.)

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Sun, B., He, F., Gao, Y. et al. Prognostic impact of visit-to-visit glycemic variability on the risks of major adverse cardiovascular outcomes and hypoglycemia in patients with different glycemic control and type 2 diabetes. Endocrine 64, 536–543 (2019). https://doi.org/10.1007/s12020-019-01893-1

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