Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in Patients with T2DM: A Cross-Sectional Controlled Study

Diabetes Ther https://doi.org/10.1007/s13300-018-0519-9 ORIGINAL RESEARCH Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in Patients with T2DM: A Cross-Sectional Controlled Study Lingling Xu . Xiaopu Lin . Meiping Guan . Yingshan Liu Received: August 22, 2018 Ó The Author(s) 2018 ABSTRACT Introduction: Early detection of diabetic peripheral neuropathy (DPN) is critical in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted therapy for DPN. We have investigated the relationship between different stages of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria can be used as an early warning signal of DPN progression. Methods: A total of 217 T2DM patients who met the inclusion criteria were recruited from the Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016. These patients were placed in groups based on Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.7133672. Lingling Xu and Xiaopu Lin contributed equally to this work. L. Xu (&) Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen, China e-mail: X. Lin Department of Huiqiao Building, Nanfang Hospital, Southern Medical University, Guangzhou, China M. Guan
Y. Liu Department of Endocrinology, Nanfang Hospital, Southern Medical University, Guangzhou, China urinary albumin excretion rate (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the Semmes–Weinstein monofilament test (SWMT) and the vibration perception threshold (VPT) test were conducted. Multiple linear regression analysis, multivariate logistic regression and receiveroperating characteristic (ROC) analysis were performed to investigate the relationship between different stages of diabetic nephropathy and DPN in these patients. Results: Significant differences were observed in the conduction velocity (CV) and amplitude of sensory/motor nerve potential among the T2DM patients at different stages of diabetic nephropathy (all p \ 0.05). The UAER and duration of diabetes were found to be independent factors associated with the mean CV and amplitude of sensory/motor nerve potential (all p \ 0.05). A disease duration of [ 10 years (p = 0.025) and a higher total cholesterol value (p = 0.024) were found to be significantly associated with abnormal SWMT results. A UAER of [ 300 mg/24 h (p = 0.007) and a diastolic blood pressure of [ 100 mmHg (p = 0.042) were associated with a higher risk for abnormal VPT. A UAER of [ 300 mg/24 h (p \ 0.001) and a disease duration of[10 years (p = 0.02) were observed to be significantly correlated with DPN. The ROC analysis showed that the optimal cutoff values of UAER and duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both p \ 0.001). Diabetes Ther Conclusions: The results suggest that diabetic nephropathy is closely associated with the development of DPN in T2DM patients and that UAER and disease duration can be used as warning indicators of DPN progression. Chinese Clinical Trials Register Number: ChiCTR-ROC-16007701. Keywords: Diabetic nephropathy; peripheral neuropathy; Urinary excretion rate Diabetic albumin INTRODUCTION Type 2 diabetes mellitus (T2DM) is a group of chronic and systemic metabolic diseases, the prevalence of which has reached epidemic proportions worldwide [1]. Due to microvascular and macrovascular complications, T2DM is associated with increased morbidity and mortality [2]. Nephropathy and neuropathy are two common complications of T2DM that seriously affect patients’ quality of life; they are also the leading causes of disability and death in T2DM patients. The clinical treatment of T2DM patients prioritizes stratification of the risk of various complications at the preclinical stage, during which time the damage is incipient and clinical interventions are likely to be the most effective in preventing progression to more advanced stages. For example, the urinary albumin excretion rate (UAER) at the microalbuminuria stage is considered to be a marker of incipient renal injury in diabetes, and its measurement as a prognostic marker has become firmly entrenched in clinical practice [3]. It has also been noted that once microalbuminuria is present, the average reduction in the creatinine clearance rate in untreated T2DM patients is approximately 10–12 mL/min per year [4]. Thus, determination of the presence or absence of microalbuminuria affects the choice of interventions that may prevent progression to further kidney injury several years before its actual development. Diabetic peripheral neuropathy (DPN) also appears before the onset of symptoms. This condition is known to be the main initiation factor for foot ulceration and lower extremity amputation [5]. About one-third of patients with DPN develop pain, which has severe consequences on the quality of life [5, 6]. Despite DPN being the most common complication of diabetes, many of its underlying pathophysiological mechanisms are unknown, and there is a lack of targeted therapy. Consequently, early diagnosis and treatment initiation are critical, with identification at an early stage likely providing an opportunity for effective intervention [7, 8]. Thus, objective tests and prognostic markers that can be used to identify DPN during its early stage are critical. Nerve conduction studies (NCSs) are considered to be the most accurate and reliable methods for detecting DPN [9–11] and ideally should be performed routinely in all patients with T2DM. However, NCSs are extremely costly in terms of financial and human resources, thus limiting their routine use. Screening for albuminuria is a routine clinical examination and commonly carried out in T2DM patients at admission to the hospital. The primary aim of this study was to evaluate the possible close correlation between different stages of diabetic nephropathy and the occurrence of DPN. Additionally, we attempted to elucidate whether albuminuria can be used as a warning signal of DPN progression, with the aim to select T2DM patients at high risk of DPN for early screening and intervention. METHODS Study Design This was a cross-sectional, open-label, controlled clinical study, with the aim to investigate the association between different stages of diabetic nephropathy and neuropathy. All procedures performed in the study are in accordance with the Ethics Committee of Nanfang Hospital, Southern Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. The Diabetes Ther Chinese Clinical Trials Registration Number of the present study is ChiCTR-ROC-16007701. Participants A total of 259 patients with T2DM were initally recruited from the Department of Endocrinology of Nanfang Hospital between January 2016 an (...truncated)