血清网膜素-1与糖尿病周围神经病变的相关性

DOI: 10.3969/j.issn.1005-82.2019.14.025文章编号： 1005-82（2019）14-0114-04

血清网膜素-1与糖尿病周围神经病变的相关性

裴翔，欧阳茹，黎宗保

（海南省第三人民医院，海南 三亚 572000）

摘要：目的 探讨血清网膜素-1与糖尿病周围神经病变（DPN）的相关性。方法 选取2016年6月— 2017年10月海南省第三人民医院收治的100例2型糖尿病患者，根据是否合并周围神经病变，将其分为DPN和无DPN组，各50例。另选取同期该院健康体检者50例作为对照组。测量各组的体重、身高、腰围、臀围，计算体重指数（BMI）及腰臀比（WHR）；检测空腹血糖（FPG）、空腹胰岛素（Fins）、糖化血红蛋白（HbA1C）、24 h尿白蛋白排泄率（24 hUAER）、胱抑素C（Cys-C）、胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）及血清网膜素-1水平，计算胰岛素抵抗指数（HOMA-IR）和胰岛β细胞功能指数（HOMA-β）。结果 各组BMI、WHR、TG、Fins、FPG、HOMA-IR、HbAlc、血清网膜素-1、HDL-C及HOMA-β比较，差异有统计学意义（P <0.05），DPN组和无DPN组患者血清网膜素-1水平均低于对照组（P <0.05），DPN组患者血清网膜素-1水平均低于无DPN组（P <0.05）。血清网膜素-1水平与HOMA-β呈正相关（r =0.496，P =0.000），与病程、WHR、TG、Cys-C、FPG、HbA1c及24 hUAER呈负相关（r =-0.323、-0.127、-0.173、-0.326、-0.449、-0.328和-0.331，P =0.009、0.013、0.035、0.000、0.000、0.000和0.023）。Logistic回归分析结果表明血清网膜素-1是影响DPN发生的危险因素[O^R=1.011（95%CI：1.003，1.019），P =0.013]。结论 DPN的发生、发展可能与血清网膜素-1水平降低有关。

关键词：  糖尿病神经病变；糖尿病，2型；Logistic模型

中图分类号：  R587.1                                               文献标识码：  A

Correlation between serum omentin-1 and diabetic

peripheral neuropathy

Xiang Pei, Yang-ru Ou, Zong-bao Li

(the Third People’s Hospital of Hainan Province, Sanya, Hainan 572000, China)Abetract: Objective To investigate the relationship between serum omentin-1 and diabetic peripheral neuropathy. Methods Totally 100 patients with type 2 diabetes mellitus (T2DM) admitted to our hospital from June 2016 to October 2017 were divided into non-diabetic peripheral neuropathy (Non-DPN) group and diabetic peripheral neuropathy (DPN) group, 50 patients of each group. Another 50 healthy subjects were selected as the control group. The body mass, height, waist circumference and hip circumference of each group were measured and body mass index (BMI) and waist-hip ratio (WHR) were calculated. The levels of fasting blood glucose (FPG), fasting insulin (Fins), HbA1C, 24 hours urinary albumin (Cys-C), cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) and serum omentin-1 were detcected. The calculated insulin resistance index (HOMA-IR) and pancreatic β-cell function index (HOMA-β) were calculated. Results There were significant differences in BMI, WHR, TG, Fins, FPG, HOMA-IR, HbAlc, serum omenin-1, HDL-C and HOMA-beta among groups (P < 0.05). Serum retinal-1 levels in patients with DPN and Non-DPN were higher than those in the control

收稿日期：2019-01-19

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group (P < 0.05). Serum retinal-1 levels in the DPN group were lower than those in the Non-DPN group (P < 0.05). The level of serum omentin-1 was positively correlated with HOMA-β (P < 0.05), and negatively correlated with duration, WHR, TG, Cys-C, FPG, HbA1c and 24hUAER (P < 0.05). Logistic regression analysis showed that serum

omentin-1 is a risk factor of diabetic peripheral neuropathy (O^R=1.011, 95% CI: 1.003, 1.019). Conclusions The decrease of serum omentin-1 level may be involved in the development of diabetic peripheral neuropathy.

Keywords: diabetic neuropathies; diabetes mellitus, type 2; logistic models

临床研究显示，>90%糖尿病患者为2型糖尿病（type 2 diabetes mellitus, T2DM）。糖尿病性周围神经病变（diabetic peripheral neuropathy, DPN）为糖尿病常见并发症。有研究认为DPN与代谢紊乱、氧化应激、神经营养因子缺乏、血管损伤、细胞因子异常及免疫功能异常等有关

[3-4]

[2]

[1]

仪检测空腹血糖（fasting plasmaglucose, FPG）、糖化血红蛋白（glycated hemoglobin, HbA1C）、胱抑素C（cystatin C, Cys-C）、总胆固醇（total cholesterol, TC）、甘油三酯（Triacylglycerol, TG）、高密度脂蛋白（high density lipoprotein cholesterol, HDL-C）水平及低密度脂蛋白（low density lipoprotein cholesterol, LDL-C）；采用免疫比浊法测定24 h尿白蛋白排泄率（24 hour urinary albumin, 24 hUAER）；采用放射免疫法测定空腹胰岛素（fasting insulin, Fins）；采用酶联免疫吸附法（enzyme linked immunosorbent assay, ELISA）检测血清网膜素-1水平；并采用稳态模型评估法计算胰岛β细胞功能指数（islet β-cell function index, HOMA-β）和胰岛素抵抗指数（insulin resistance index, HOMA-IR），HOMA-β=20×Fins/FPG-3.5，HOMA-IR=FPG×Fins/22.5。

。网膜素是一种由网膜脂

肪组织特异性分泌的蛋白质，血清网膜素-1具有增强胰岛素敏感性、调节机体代谢平衡及舒张血管等作用

[5-7]

。因此，本研究旨在探讨血清网膜素-1与DPN

的相关性。

1 资料与方法1.1 临床资料

选取2016年6月—2017年10月海南省第三人民医院收治的100例T2DM患者。纳入标准：①T2DM的诊断符合WHO（1999年）糖尿病诊断标准

[8]

；②DPN的诊断符合《中国T2DM防治指南》

[9]

1.3 统计学方法

数据分析采用SPSS 18.0统计软件。计量资料以均数±标准差（x±s）表示，比较用t检验或方差分析，进一步的两两比较用LSD-t检验；相关分析用Pearson法；危险因素采用Logistic回归分析，P <0.05为差异有统计学意义。

（2013年）标准；③感觉神经定量检测仪检测结果

显示感觉过敏或减退；④同意签署临床研究知情同意书。排除标准：①其他类型糖尿病患者；②合并糖尿病急性并发症患者；③合并其他疾病所致神经病变患者；④严重心、肝、肾功能障碍患者；⑤长期接触可能导致周围神经损害药物患者；⑥长期酗酒者。根据是否合并周围神经病变，将患者分为无DPN组和DPN组，每组50例。其中无DPN组男性27例，女性23例；年龄43～71岁，平均（55.4±9.2）岁。DPN组男性26例，女性24例；年龄42～73岁，平均（54.9±10.1）岁。另选同期本院体检健康群众50例作为对照组。其中，男性27例，女性23例；年龄40～72岁，平均（54.6±10.1）岁。本研究得到本院伦理委员会审查批准。

2 结果

2.1 各组生化及代谢指标比较

各组BMI、WHR、TG、Fins、FPG、HOMA-IR、 HbAlc、血清网膜素-1、24 hUAER、HDL-C及HOMA-β比较，差异有统计学意义（P <0.05），DPN组血清网膜素-1低于无DPN组（P <0.05）。见 表1。

1.2 方法

测量各组体重、身高，计算体重指数（body mass index, BMI）=体重/身高，测量腰围、臀围，计算腰与臀比例（waist-to-hip ratio, WHR）=腰围/臀围；采集各组清晨空腹静脉血5 ml，采用全自动生化分析

2.2 血清网膜素-1与各项指标的相关性分析

血清网膜素-1水平与HOMA-β呈正相关（r =0.496，P =0.000），与病程、WHR、TG、Cys-C、FPG、HbA1c及24 hUAER呈负相关（r =-0.323、 -0.127、-0.173、-0.326、-0.449、-0.328和-0.331，

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中国现代医学杂志 第29卷

表1 各组生化及代谢指标比较 （n =50，x±s）

组别对照组无DPN组DPN组

病程/年-5.91±2.166.22±2.450.6710.50424 hUAER/（mg/24 h）-47.25±11.11.13±17.2415.1000.000BMI/（kg/m）22.14±2.3525.81±2.4726.46±2.522.0190.0372WHR0.86±0.030.92±0.040.93±0.041.9760.043TC/（mmol/L）TG/（mmol/L）4.07±0.244.41±0.734.±0.630.8360.102HOMA-β95.11±28.2844.92±12.0930.12±7.0811.0360.0001.08±0.352.42 ±0.422.53±0.512.5370.029HDL-C/ （mmol/L）1.29±0.151.02 ±0.141.08±0.092.2040.032LDL-C/ （mmol/L）2.74±0.323.07±0.723.69±0.870.6290.317HbA1C/%4.79±0.328.93±0.997.87±0.635.2490.000Cys-C/（mg/L）0.97±0.051.02±0.041.06±0.071.0120.226血清网膜素-1/（μg/L）47.61±9.1326.82±7.7217.45±6.027.0420.000F值P值组别对照组无DPN组DPN组

Fins/（μIU/ml）FPG/（mmol/L）6.32±1.6711.08±2.1810.09±2.344.0610.0004.22±0.249.53±1.7112.76±2.913.1790.012HOMA-IR1.50 ±0.1.14±0.434.34±0.323.7120.000F值P值P =0.009、0.013、0.035、0.000、0.000、0.000和0.023），与BMI无相关性（r =-0.062，P =0.496）。

TG、Cys-C、24 hUAER、FPG、HbAlc、Fins、HOMA-IR及血清网膜素-1作为自变量，进行Logistic回归分析，结果表明血清网膜素-1是影响DPN发生的危险因素（P <0.05）。见表2。

2.3 DPN危险因素的Logistic回归分析

将有DPN作为因变量，将病程、BMI、WHR、

表2 DPN危险因素的Logistic回归分析参数

自变量血清网膜素-1b0.011Sb0.005Wald χ6.2482P值0.013O^R1.01195% CI下限1.003上限1.0193 讨论

神经病变为糖尿病患者最为常见的并发症，可累及自主神经、周围神经、颅神经及脑及脊髓。其中DPN是糖尿病神经病变最常见的一种，约占75%左右。最近的流行病学调查研究显示，随着糖尿病患者病程的延长，糖尿病周围神经病变的发病率呈逐渐上升趋势。迄今为止，DPN的确切病因及发病机制尚不清楚，普遍认为DPN是多因素共同作用的结果。有研究报道，DPN的发生与遗传因素、氧化应激、代谢紊乱（如多元醇途径、糖基化终末产物形成）、神经营养因子缺乏、血管损伤、细胞因子异常及免疫功能异常等密切相关

[14-15]

[13]

[12]

[11]

[10]

是近年来发现的一种表达于机体网膜脂肪组织的脂肪因子，其是在机体代谢失衡状态下分泌的一种保护性因子

[18]

。有研究发现，血清网膜素-1可通过增强胰

岛素信号通路中蛋白激酶B磷酸化，以促进脂肪细胞对胰岛素介导的葡萄糖的摄取，同时兼具调节代谢平衡、舒张血管及抗炎等多种生物学作用

[19-21]

。

本研究结果显示，DPN组和无DPN组患者血清网膜素-1水平低于对照组，相关性分析结果显示，血清网膜素-1水平与HOMA-β呈正相关，与病程、WHR、TG、Cys-C、FPG、HbA1c、24 hUAER呈负相关，这与AMINILARI等

[17]

学者的研究结果类似，提示血

。清网膜素-1可能是一种保护性的脂肪因子，不仅可增强胰岛素活性，改善胰岛素抵抗，调节糖代谢，还在脂代谢中发挥重要作用。此外，Logistic回归分析结果显示，血清网膜素-1是影响DPN发生的危险因素，

既往研究显示，脂肪因子在机体胰岛素抵抗、脂代谢、免疫、炎症、代谢综合征、心血管疾病及T2DM的发生发展过程中发挥重要作用

[16-17]

。网膜素

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这提示血清网膜素-1可能参与了DPN的发生发展，这与ELSAID等

[22]

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levels and diabetic peripheral neuropathy in patients with type 2 diabetes: a cross-sectional study using electronic health records[J]. J Diabetes Res, 2017, 2017(2): DOI: 10.1155/2017/2835981.[16] NANDA B, MAHAPATRA S, DEVI N, et al. Study of serum

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（李科 编辑）

学者的研究报道一致。

综上所述，DPN患者血清网膜素-1水平的降低可能参与了DPN的发生发展过程。同时，本研究也存在不足之处，由于本研究样本量偏少，今后仍需加大相关样本量的收集，进行深入探究，以期为临床提供更有价值的参考。

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