新诊断2型糖尿病患者血清硫氧还蛋白、硫氧还蛋白相互作用蛋白与颈动脉粥样硬化的相关性

Association of serum thioredoxin and thioredoxin-interacting protein with carotid atherosclerosis in newly-diagnosed type 2 diabetic patients

摘要:

目的  探讨新诊断2型糖尿病（T2DM）患者血清硫氧还蛋白（Trx）、硫氧还蛋白相互作用蛋白（TXNIP）水平与颈动脉粥样硬化（CAS）的相关性。方法  选取2014年2月-2015年11月于河北省唐山市工人医院内分泌科就诊的新诊断T2DM患者160例作为病例组。根据颈动脉超声检查结果将患者分为T2DM伴CAS组（CAS组，n=65例）和T2DM不伴CAS组（NCAS组，n=95例）。同时从医院健康体检中心选取非糖尿病健康人群140例作为正常组。记录其年龄、性别、体重指数（BMI）、收缩压（SBP）、舒张压（DBP），收集其临床检验结果，包括空腹血糖（FPG）、空腹胰岛素（FINS）、糖化血红蛋白（HbA1C）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、同型半胱氨酸（Hcy），计算胰岛素抵抗指数（HOMA-IR）。采用酶联免疫吸附法（ELISA）检测血清Trx、TXNIP含量，采用胰岛素还原法检测血清Trx活性。结果  与正常组比较，T2DM患者FPG、HbA1c、HOMA-IR、Trx、TXNIP水平升高，Trx活性下降（均P <0.05）；T2DM患者CAS组较NCAS组年龄较大，FPG、HbA1c、SBP、Trx、TXNIP水平较高，Trx活性下降（均P <0.05）；在T2DM患者中，Trx与HbA1c呈正相关，TXNIP与HbA1c、HOMA-IR呈正相关，Trx活性与TXNIP呈负相关（均P <0.05）；在T2DM患者中，年龄、HbA1c、Trx、TXNIP及Trx活性为合并CAS的影响因素，其中年龄（■=1.134，P =0.032）、HbA1c（■=1.275，P =0.021）、Trx（■=1.532，P =0.015）、TXNIP（■=1.731，P = 0.005）为CAS发生的危险因素，而Trx活性（■=0.507，P =0.002）为CAS发生的保护因素。结论  新诊断T2DM患者血清Trx、TXNIP、Trx活性与其CAS相关，提示Trx系统可能参与了CAS的发生及发展。

Abstract:

Objective To investigate the association of serum thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP) with carotid atherosclerosis (CAS) in newly-diagnosed type 2 diabetic patients. Methods Totally 160 patients newly diagnosed as T2DM in the Department of Endocrinology of Tangshan Gongren Hospital were recruited and divided into two groups according to the result of carotid artery ultrasonography, i.e. T2DM with CAS group (CAS group, 65 cases) and T2DM without CAS group (NCAS group, 95 cases). During the same period, 140 healthy controls without T2DM from the Medical Examination Center were recruited. Data including age, sex, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), insulin (FINS), glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and homocysteine (Hcy) were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated by FPG (mmol/L) × FINS (mU/L)/22.5. Serum Trx and TXNIP were measured by enzyme-linked immunosorbent assay (ELISA), and Trx activity was measured by insulin reduction assay. Results Compared with the normal controls, FPG, HbA1c, HOMA-IR, Trx and TXNIP levels in the T2DM patients increased, but Trx activity decreased (all P < 0.05). Compared with the NCAS group, the patients in the CAS group were older, with higher FPG, HbA1c, SBP, Trx and TXNIP levels and lower Trx activity (all P < 0.05). In the T2DM patients, Trx was positively correlated with HbA1c; TXNIP was positively correlated with HbA1c and HOMA-IR, but inversely correlated with Trx activity (all P < 0.05). In the T2DM patients, age, HbA1c, Trx, TXNIP and Trx activity were the influence factors of CAS. Age (■ = 1.134, P = 0.032), HbA1c (■ = 1.275, P = 0.021), Trx (■ = 1.532, P = 0.015) and TXNIP (■ = 1.731, P = 0.005) increased the incidence of CAS, but Trx activity (■ = 0.507, P = 0.002) was a protective factor for CAS. Conclusions Serum Trx, TXNIP and Trx activity are closely correlated with carotid atherosclerosis in newly-diagnosed type 2 diabetic patients, suggesting that Trx system may be involved in occurrence and development of carotid atherosclerosis of these patients.