Elsevier

Clinica Chimica Acta

Volume 502, March 2020, Pages 159-166
Clinica Chimica Acta

Impact of HbA1c variability on subclinical left ventricular remodeling and dysfunction in patients with type 2 diabetes mellitus

https://doi.org/10.1016/j.cca.2019.12.006Get rights and content

Highlights

  • Adverse changes in LV structure and function were observed after 4.7-year follow-up.

  • SD-HbA1c was positively associated with changes in LV structure and E/e' ratio.

  • SD-HbA1c was negatively associated with changes in LVEF and E/A ratio.

  • SD-HbA1c predicted LV remodeling and dysfunction independently of mean HbA1c.

Abstract

Background

Glycemic instability confers a risk of poor prognosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate whether HbA1c variability provided additional value over mean HbA1c for predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

Methods

A total of 466 T2DM patients with normal cardiac structure and function were recruited and prospectively followed up for a median of 4.7 y. HbA1c was measured quarterly. The intrapersonal mean and standard deviation (SD) of HbA1c measurements were calculated, and SD-HbA1c was considered as a measure of HbA1c variability. All participants underwent transthoracic echocardiography at baseline and after follow-up.

Results

In multivariable regression analyses, SD-HbA1c was independently associated with annualized changes in left ventricular end diastolic diameter, interventricular septum, left ventricular posterior wall, left ventricular mass index, left ventricular ejection fraction, E/e' ratio, and E/A ratio (P < 0.001). Subgroup analysis based on mean HbA1c levels (<7.0%, 7.0–7.5%, and ≥7.5%) further confirmed that SD-HbA1c was associated with most of the above parameters regardless of mean HbA1c levels.

Conclusion

This study indicates that HbA1c variability adds to the mean value in predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

Introduction

As a major public health concern, heart failure (HF) is the leading cause of hospitalization for individuals aged ≥ 65 y [1]. This problem is magnified in patients with type 2 diabetes mellitus (T2DM), since T2DM dramatically increases the risk of HF [2]. Several large sets of clinical data have demonstrated a 2- to 5-fold excess risk for developing HF in individuals with T2DM than those in the general population [3]. The HF in T2DM patients is associated with higher health care expenses and worse outcomes [4]. Data from large clinical trials suggested that patients with T2DM and HF had 4- to 10-fold higher mortality compared with T2DM without HF [5], [6], [7], [8]. Studies show that T2DM contributes to the development of HF through its relation to other diseases, including coronary artery disease and arterial hypertension, in addition to the direct deleterious effect of DM on the myocardium. Despite previous findings highlight the clinical importance of the association of HF and T2DM, a statement from the Heart Failure Association of the European Society of Cardiology points out that HF is often unrecognized in T2DM patients [2]. An observational study indicated a very high prevalence (27.7%) of previous unknown HF and left ventricular dysfunction in patients with T2DM [9], which emphasizes the importance of an active search for subclinical disorders in cardiac structure and function in patients with T2DM.

The clinical risk variables of HF in T2DM patients have been widely studied. Glycemic control (HbA1c and fasting glucose), insulin use, increasing age and coronary artery disease are thought to be the most common clinical variables associated with significantly increased risk of HF in T2DM patients [10]. Among them, an almost linear increase in risk is observed between HbA1c and HF, where each 1% elevation in HbA1c leads to an 8% increase in the frequency of HF. Even in T2DM patients without clinical HF, HbA1c remained associated with the echocardiographic parameters of preclinical left ventricular systolic and diastolic dysfunction. Therefore, HbA1c is considered as a good predictor for the development of cardiac dysfunction in T2DM patients. However, even within the same mean HbA1c levels, individuals can vary widely in their glycemic excursions [11]. More and more studies found that HbA1c variability may be an additional risk factor, independently of mean HbA1c, for the development of the microvascular and macrovascular complications in T2DM patients [12]. To date, unfortunately, there have been no studies assessing the association between HbA1c fluctuations and cardiac dysfunction in diabetic patients.

Section snippets

Study population

This prospective, longitudinal cohort study was approved by the Institutional Review Board of the Third Affiliated Hospital, Sun Yat-sen University. The study population consisted of consecutive patients with T2DM of Chinese, Asian, who were prospectively assessed for complications at the department of Endocrinology from January 2013 to December 2014. Subjects were eligible to participate in the study if they: (1) were ≥18 y; (2) were diagnosed as T2DM according to 1999 World Health

Patients characteristics

A total of 721 consecutive patients with T2DM (420 men and 301 women) were enrolled in the study from January 2013 to December 2014. During a median of 4.7 y of follow-up, 128 participants without final echocardiography examination and 113 participants with less than five HbA1c measurements were excluded. Another 14 individuals who developed myocardial infarction during follow-up period were also excluded. Finally, the remaining 466 participants (222 men and 244 women; mean age was 59.1 ± 11.7

Discussion

We demonstrated that HbA1c variability, represented by SD-HbA1c, was associated with the adverse changes in left ventricular structure, systolic and diastolic function in patients with T2DM over a median follow-up period of 4.7 y, independently of mean glucose control status and other conventional risk factors. Our study suggested that increase in the long-term glycemic variability might additionally predict the long-term left ventricular remodeling and dysfunction in patients with T2DM.

T2DM is

Limitations

There were a few limitations in this study. First, SD of HbA1c may be overestimated among patients with variant number of HbA1c measurements. Second, the possibility of residual confusion due to unmeasured or unknown risk factors remains. Third, the observational study only show the association, clinical trials are need to investigate the beneficial effects of reducing glycemia variability to elucidate any direct causality. Finally, this was a single center study in China. The uncertainty of

Conclusion

Our study demonstrated that HbA1c variability in patients with T2DM was associated with the long-term subclinical adverse change in LV structure and function, independently of mean HbA1c. As HbA1c variability is considered as a predictor factor, a reasonable and stable glucose control by individualized treatment may be needed to prevent further cardiac damage.

CRediT authorship contribution statement

Suhua Li: Conceptualization, Writing - review & editing, Funding acquisition. Zhenda Zheng: Investigation, Data curation. Xixiang Tang: Formal analysis, Writing - original draft, Visualization. Junlin Zhong: Investigation, Resources. Xing Liu: Investigation. Yunyue Zhao: Validation. Lin Chen: Validation. Jieming Zhu: Investigation, Supervision, Project administration. Jinlai Liu: Methodology, Writing - review & editing, Funding acquisition. Yanming Chen: Conceptualization, Writing - review &

Acknowledgements

This work was supported by National Key R&D Program of China, the General Program of National Natural Science Foundation of China, the 5010 Clinical Research Projects of Sun Yat-sen University, the Science and Technology Plan Projects of Guangdong Province, the Key Special Projects of Medical and Health Collaborative Innovation of Guangzhou City, the Key Area R&D Program of Guangdong Province, the Special Scientific Research Project of Guangzhou City, the Science and Technology Plan Project of

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    These authors contributed to the work equally.

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