Objective: To explore the relationship between serum cystatin-C (Cys-c) levels and vibrating perception threshold (VPT) in patients with Type 2 diabetes mellitus (T2DM).
Methods: According to the symptoms, signs and results of lab examination, a total of 352 patients with T2DM were divided into a diabetic peripheral neuropathy group (DPN group, n=107) and a non-diabetic peripheral neuropathy group (NDPN group, n=245). Serum Cys-c levels were measured by radioimmunoassay method. The relationship between serum Cys-c levels and VPT, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), glucose and blood pressure and other parameters were also analyzed by correlation and multiple regression analysis. All T2DM patients were divided into a high Cys-c levels group (n=89) and a low Cys-c levels group (n=263) according to the upper quartile of Cys-c, and the incidence of DPN and VPT levels in each group were compared. Risk factors of DPN in T2DM patients were analyzed by binary logistic regression analysis and receiver operating characteristic (ROC) curve was used to identify the optimal cutoff of serum Cys-c levels for predicting DPN in patients with T2DM.
Results: Serum Cys-c levels were significantly higher in the DPN group than that in the NDPN group [(1.04±0.43) vs (0.80±0.25) mg/L, P<0.01]. Correlation analysis showed that serum Cys-c levels were positively correlated with age, body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), ACR, VPT, pulse pressure (PP), white blood cell( WBC) , red cell distribution width (RDW), hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) (r=0.410, 0.115, 0.613, 0.433, 0.291, 0.300, 0.156, 0.129, 0.282, 0.314, 0.236, respectively, P<0.05 or P<0.01); and negatively correlated with diastolic blood pressure (DBP), eGFR and indirect bilirubin (IBIL) (r=-0.135, -0.647, -0.114, respectively, P<0.05 or P<0.01). Serum Cys-c levels in T2DM patients were positively correlated with VPT after adjusting for gender, age, BMI, ACR and eGFR (r=0.235, P<0.01). Multiple regression analysis revealed that VPT, age, SCr, eGFR, PP, ACR and HbA1C were independent related factors affecting serum Cys-c levels in T2DM patients. Compared with those in the low Cys-c levels group, the prevalence rate and VPT value was increased in the high Cys-c levels group (all P<0.01). Binary logistic regression analysis found that age, Cys-c and HbA1C were independent risk factors for predicting DPN in T2DM patients (all P<0.01). ROC curve analysis revealed that the optimal cutoff of Cys-c to predict DPN in T2DM patients was 0.996 mg/L, the sensitivity was 43.9%, the specificity was 83.7%, and the area under curve was 0.663.
Conclusion: Serum Cys-c levels are well correlated with VPT in patients with T2DM. When the serum Cys-c levels>0.996 mg/L, the predicts have high risk of DPN in T2DM patients, which might be related to diabetic nephropathy, oxidative stress and inflammatory reaction induced by advanced age, hyperglycemia and hypertension.
目的：探讨2型糖尿病(Type 2 diabetes mellitus，T2DM)患者血清胱抑素C(cystatin-C，Cys-c)与振动感觉阈值(vibrating perception threshold，VPT)之间的关系。方法：选择352例T2DM 患者，根据症状、体征和实验室检查分为神经病变组(DPN组，n=107)和非神经病变组(NDPN组，n=245)，采用放射免疫分析法测定血清Cys-c水平，分析Cys-c与VPT，预估肾小球滤过率(estimated glomerular filtration rate，eGFR)﹑尿微量白蛋白/肌酐(urinary albumin-to-creatinine ratio，ACR)和血糖血压等指标的关系。将T2DM患者以Cys-c上四分位为切点分为高Cys-c组(n=89)和低Cys-c组(n=263)，比较两组间神经病变患病率及VPT水平。应用Binary logistic回归分析T2DM患者发生周围神经病变的危险因素。采用受试者工作特征(receiver operating characteristic，ROC)曲线评估Cys-c预测T2DM患者发生周围神经病变的最佳界值。结果：DPN组血清Cys-c水平明显高于NDPN组(1.04±0.43 vs 0.80±0.25 mg/L，P<0.01)。T2DM患者血清Cys-c与年龄，体质量指数(body mass index，BMI)，血肌酐(serum creatinine，SCr)，血尿素氮(bloold urea nitrogen ，BUN) ，ACR，VPT﹑脉压(pulse pressure，PP)，白细胞计数(white blood count，WBC)，红细胞分布宽度(red blood cell distribution width，RDW)，糖化血红蛋白(hemoglobin A1c，HbA1C)和空腹血糖(fasting blood glucose，FBG)呈正相关(分别r=0.410，0.115，0.613，0.433，0.291，0.300，0.156，0.129，0.282，0.314，0.236，分别P<0.05或P<0.01)；与舒张压(diastolic pressure，DBP)，eGFR和间接胆红素(indirect bilirubin，IBIL)呈负相关 (r=−0.135，−0.647，−0.114，分别P<0.05或P<0.01)。校正性别，年龄，BMI，ACR和eGFR后，T2DM患者Cys-c与VPT仍呈明显正相关(r=0.235，P<0.01)。VPT，年龄，SCr﹑eGFR，PP ，ACR和HbA1C是影响T2DM患者血清Cys-c水平的独立相关因素。高Cys-c组周围神经病变患病率和VPT水平明显高于低Cys-c组(均P<0.01)。Logistic回归分析显示年龄、Cys-c和HbA1C是预测T2DM患者周围神经病变发病的独立危险因素(均P<0.01)。ROC曲线显示：Cys-c界值为0.996 mg/L时，预测T2DM发生DPN的敏感度为43.9%，特异度为83.7%，ROC曲线下面积为0.663。结论：糖尿病肾病患者血清Cys-c水平与VPT关系密切，Cys-c>0.996 mg/L者发生周围神经病变的风险增加，其机制可能与糖尿病肾病、高龄及高血糖或高血压所致的氧化应激和炎症反应有关。.