视黄醇结合蛋白4与2型糖尿病患者下肢缺血相关

Relationship between serum retinol-binding protein 4 with lower limb ischemia in Chinese type 2 diabetic patients

目的 检测2型糖尿病（T2DM）下肢缺血患者（LLI）和非下肢缺血患者（NLLI）的血清视黄醇结合蛋白4（RBP4）水平,探讨RBP4与T2DM下肢缺血的相关性.方法 选取2011年7月至2012年6月在上海市糖尿病临床医学中心门诊就诊和住院的T2DM患者共755例为研究对象,踝肱指数（ABI） ＜0.9和下肢血管超声提示动脉狭窄〉50％诊断为LLI,参照此标准将患者分为两组：LLI组（n=105）和NLLI组（n=650）.检测所有患者体质指数（BMI）、腰围、血压、RBP4、血糖、血脂、预估肾小球滤过率（eGFR）、下肢动脉内膜厚度（IMT）等,比较两组间临床特征及RBP4水平差异.按照RBP4四分位数分组,比较各组问临床特征的差异及LLI的发生率.两两比较采用t检验,多组间比较采用单因素方差分析,采用Spearman进行相关性分析.结果 LLI组和NLLI组两组间年龄、糖尿病病程、收缩压（SBP）、总胆固醇（TC）、血清RBP4水平以及高血压、冠心病和脑梗死的发生率差异有统计学意义[分别为（72±9）比（57±12）岁,13（8～20）比8（4～13）年,（140±20）比（130±18） mmHg（1 mmHg=0.133 kPa）,（4.7±1.0）比（4.5±1.1） mmol/L,47（37～54）比43（37～51） mg/L,80％比50.7％,24.8％比10.9％,22.9％比6.8％,t=16.48、5.84、3.45、-2.07、2.16,Х^2=31.40、15.40、28.29;均P＜0.05].Spearman相关分析表明,校正了年龄、病程、eGFR、高血压后,血清RBP4与TC、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、空腹C肽、餐后2 hC肽、IMT呈正相关（r=0.27、0.37、0.12、0.17、0.24、0.10,均P＜0.05）.Logistic回归分析表明年龄、高血压和RBP4是下肢缺血的独立影响因素（OR=1.166、2.297、1.023,均P＜0.05）.按照RBP4四分位数分组,结果看到随着RBP4水平升高,BMI、腰围、SBP、IMT、TC、TG和LDL-C增加（F=4.31、7.44、8.01、2.99、15.81、28.27、3.99,均P＜0.05）.四组间LLI发生率差异具有统计学意义（Х^2=11.661,P＜0.05）.结论 RBP4和T2DM下肢缺血相关,T2DM患者高血清RBP4水平提示下肢缺血患病风险增加.

Objective This study tested serum retinol-binding protein 4 （RBP4） level in type 2 diabetic mellitus （T2DM） patients with lower limb ischemia （LLI） and non-lower limb ischemia （NLLI） to investigate the relationship between serum retinol-binding protein 4 levels and lower limb ischemia in type 2 diabetic population.Methods A total of 755 type 2 diabetic in-patients and out-patients in Shanghai Clinical Medical Center from Jul 2011 to Jun 2012 were included in this cross-sectional study.Their clinical and biochemical characteristics,ankle-brachial index （ABI）,lower extremity arterial ultrasound were detected.LLI was defined by ABI〈 0.9 and lower extremity arterial stenosis〉50% by ultrasound examination.According this standard,patients were divided to two groups：LLI group （n=105） and NLLI group （n=650）.Body mass index （BMI）,waist circumference,blood pressure,RBP4,blood glucose,serum lipid,estimated glomerular filtration rate （eGFR）,intima-meida thickness （IMT） were measured to compare the difference of clinical character and RBP4 level between two groups.The patients were grouped by the quartiles of RBP4 to compare the difference of clinical character and the incidence of LLI.Two groups of continuous variables were compared by the t test.Multiple groups of continuous variables were compared by ANOVA test.The association between RBP4 and other variables were evaluated with Spearman correlation.Results There were significant differences in age （（72 ±9） vs （57 ± 12） yrs,t=16.48,P〈0.05）,duration of diabetes （（13 （8-20） vs 8 （4-13） yrs,t=5.84,P〈0.05）,systolic blood pressure （SBP （140±20） vs （130± 18） mmHg,t=3.45 P〈0.05）,total cholesterol （TC （4.7±1.0） vs （4.5± 1.1） mmol/L,t=-2.07,P〈0.05）,serum RBP4 （（47（37-54） vs 43（37-51） mg/L,t=2.16,P〈0.05） and incidence of hypertension （80.0% vs 50.7%,Х^2=31.40,P〈0.05）,coronary artery disease （24.8% vs 10.9%,Х^2=15.40,P〈0.05）,cerebral infarction （22.9% vs 6.8%,Х^2=28.29,P〈0.05） between LLI group and NLLI group.After adjusting for age,duration,eGFR and hypertension,Spearman correlation analysis showed that serum RBP4 level was positively correlated with TC,triglyceride （TG）,low density lipoprotein-cholesterol （LDL-C）,fasting C-peptide,2 h-postprandial C-peptide,IMT （r=0.27,0.37,0.12,0.17,0.24,0.10,respectively,P〈0.05）.Logistic regression analysis showed that age,hypertension,RBP4 were independent associated factors for LLI （OR=1.166,2.297,1.023,P〈0.05 all above）.Comparisons of patients with quartiles of RBP4 revealed that the levels of BMI,waist circumference,SBP,IMT,TC,TG,LDL-C level increased with the increasing of serum RBP4 concentration （F=4.31,7.44,8.01,2.99,15.81,28.27,3.99,P〈0.05）.There was significant difference in the incidence of LLI between four groups （Х^2=11.66 P〈0.05）.Conclusions RBP4 was associated with lower limb ischemia in type 2 diabetic patients.High serum RBP4 concentration predicts the increasing risk of lower limb ischemia in type 2 diabetic patients.