Neutrophil-to-lymphocyte ratio is associated with diabetic peripheral neuropathy in type 2 diabetes patients

https://doi.org/10.1016/j.diabres.2017.05.008Get rights and content

Highlights

  • T2DM patients with higher NLR levels tend to have higher NVC and VPT results.

  • T2DM patients with higher NLR levels are more likely to develop DPN.

  • NLR is related to DPN, VPT, NCV, age and FPG in T2DM patients.

  • NLR could be a predictor of DPN.

Abstract

Objective

Diabetic peripheral neuropathy (DPN) had been demonstrated as a chronic inflammation state and one of the most common complications of type 2 diabetes mellitus (T2DM). Neutrophil-to-lymphocyte ratio (NLR) is a novel marker to reflect many kinds of chronic inflammation disease including diabetes. We aim to evaluate the association between NLR and DPN and to determine whether NLR could be a new indicator of DPN in type 2 diabetes patients.

Methods

We retrospect the consecutive medical files of T2DM patients. Nerve conduction velocity (NCV), vibration perception threshold (VPT) and the data for complete blood count were recorded. Patients were divided into tertiles based on admission NLR values. Clinical parameters were firstly compared among groups. Then, logistic regression and ROC analysis were performed.

Results

Percentages of DPN were 42.60%, 54.97% and 65.50%, in the low, middle and high tertile, respectively (n = 72, 94 and 112, p < 0.05). VPT values were 13.75 ± 7.97, 15.01 ± 9.60 and 16.78 ± 10.92, respectively, (p < 0.05). NCV in different nerves decreased with the increase of NLR (p < 0.05). After adjusting potential related factors, NLR was still related to status of DPN in the logistic regression (r = 1.743, p = 0.001). Area under ROC was 0.619 (p < 0.001).

Conclusion

The present study showed that T2DM patients with higher NLR levels might be more likely to develop peripheral neuropathy complication. NLR levels grow with the increase of NCV and VPT results. As a predictor of DPN, NLR could be used in clinical practice to help doctors understand the level of DPN progression.

Introduction

Type 2 diabetes (T2DM) is a major public health problem worldwide. It is estimated that 366 million people will be affected by T2DM till the year of 2030 [1], [2]. Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes. The lifetime incidence of DPN is approximately 45% for patients with type 2 diabetes mellitus and 54–59% for patients with type 1 diabetes mellitus [3], [4]. In China, peripheral neuropathy is demonstrated to be popular among diabetics, pre-diabetics and even among normal population [5]. Therefore, emphasis should be laid on effective surveillance, early detection and diagnosis of DPN.

Pathological researches and laboratory studies have shown that low-level systemic inflammation has been implicated as the underlying mechanism responsible for the development of T2DM and subsequent complications [6], [7], [8]. However, the costs and technical difficulties associated with detecting these inflammatory markers in daily clinical practice have limited their use. Recently, a novel inflammatory biomarker has been generated to reflect both innate immune response (mediated by neutrophils) and adaptive immune response (mediated by lymphocytes) [9]. As an easily measurable laboratory index, neutrophil-to lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammation [10], [11], a risk factor of mortality after a major cardiac event and a predictor of cancer outcome [12], [13]. It was also defined as a potential biomarker of inflammation in diabetes and its complications, such as macro-vascular and nephropathy disease [14], [15].

The progression in DPN was traditionally clinically characterized by the development of vascular abnormalities. We therefore want to see if NLR could reflect DPN progression as well as vascular complications. To date, as far as we know, no study has specifically evaluated the relationship between NLR and DPN. Since the degree of DPN is assessed by nerve conduction velocity (NCV, detected by electromyogram (EMG)) and vibration perception threshold (VPT), we hypothesized that the NLR is associated with the results of VPT and EMG and could be increased during the progression of DPN. Hence, the purpose of the present study was to evaluate the association between NLR and DPN and to determine whether NLR could be a new indicator of DPN in type 2 diabetes patients.

Section snippets

Study design and patients

We retrospect the consecutive medical files of patients recorded during January 2015–February 2017 in Endocrinology and Metabolism Department of Huashan Hospital, Fudan University with the diagnosis of T2DM. For achieving data integrity, we included patients with all VPT value, EMG results and complete blood count, which were essential for the present study to identify the association between the NLR and the progression of DPN. This study was conducted under the program of Screening of Diabetic

Patient characteristics

Finally, a total number of 511 T2DM patients, who had reliable, complete and accessible medical records, were involved in our study. Patients’ demographic characteristics and laboratory findings are shown in Table 1. Patients were divided into tertiles based on admission NLR values. The first (low), second (medium), and third (high) tertiles were defined as NLR  1.52 (n = 169), 1.52 < NLR  2.20 (n = 171), and NLR > 2.20 (n = 171), respectively. Percentage of DPN patients in different NLR groups was shown

Discussion

To our best of knowledge, the present study is the first to discuss the relation between NLR and DPN. The main finding of our study is that, among T2DM patients, NLR could be a strong predictor to reflect the severity of DPN. This association remained significant even after adjusting for DPN related factors associated to NLR.

T2DM had been demonstrated as an inflammatory disease and a dysfunction status of immune system, as well as its complications [19], [20]. Inflammation, endothelial

Ethics approval

This study was conducted under the program of Screening of Diabetic Neuropathy and approved by the ethics committee of Huashan Hospital (Approval No.: 2014-250).

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Funding

The present study was supported by grants from the National Natural Science Foundation of China (81370884, to B. Lu), the Shanghai New Excellent Youth Program (XYQ2013120, to B. Lu), Fudan Zhuoxue Project (to B Lu), Pudong program from Pudong Municipal Commission of Health and Family Planning (PW2013D-2, to HL Shi and PW2014D-2, to B Lu), and Shanghai Science and Technology Committee Program (14411962200, to YM Li).

Authors’ contribution

Siying Liu and Hangping Zheng wrote the manuscript. Xiaoming Zhu and Fei Mao analyzed the data. Shuo Zhang, Hongli Shi revised the study and manuscript. Bin Lu and Yiming Li conducted the study design and quality control. All authors read and approved the final manuscript.

Disclosure

The authors declare no conflict of interest.

Acknowledgments

We thank Doctor Xintong Zhang for data collection during the revision procession.

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    These authors contributed equally to this work.

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