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脂肪酸结合蛋白4在2型糖尿病肾病中的诊断价值

Diagnostic value of fatty acid binding protein 4 in type 2 diabetic nephropathy

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目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂肪酸结合蛋白4(fatty acid-binding pro-tein 4,FABP4)与糖尿病肾病(diabetic nephropathy,DN)的相关性及其作为DN早期诊断的应用价值.方法:纳入T2DM患者218例及健康体检者(对照组)20名,收集受试者的一般临床资料如身高、体质量、腰围、糖尿病病程等,计算BMI;收集血糖、糖化血红蛋白、空腹胰岛素、空腹C肽、肝肾功能、血脂等指标,计算稳态模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance index,HOMA-IR).采用 ELISA 测定血清 FABP4 水平;采用联合血肌酐(serum creatinine,Scr)和胱抑素C(cystatin C,Cys C)的慢性肾脏病流行病学协作方程式计算肾小球滤过率;测定尿白蛋白和肌酐水平,计算尿微量蛋白与肌酐比值(urinary albumin to creatinine ratio,UACR).根据估算的肾小球滤过率(estimated glomeruilar filtration rate,eGFR)水平将T2DM患者分为肾功能正常组(eGFR≥90 mL/min/1.73 m2)、轻度肾功能不全组(eGFR 60~<90 mL/min/1.73 m2)和中度肾功能不全组(eGFR 30~<60 mL/min/1.73 m2);根据UACR水平分为正常蛋白尿组(UACR<30 mg/g)、微量蛋白尿组(UACR 30~<300 mg/g)和大量蛋白尿组(UACR≥300 mg/g).采用回归分析评估FABP4与eGFR、UACR严重程度的相关性.结果:(1)与对照组相比,T2DM患者的血清FABP4显著升高.(2)在根据eGFR分层的3个亚组中,随着eGFR的下降,血清FABP4水平显著增加(P<0.001).但在UACR亚组中差异无统计学意义(P=0.382).(3)Spearman 相关分析显示 FABP4 与 eGFR 呈负相关(r=-0.203,P=0.001),与 UACR 无相关性(r=0.130,P=0.055).(4)多元线性回归表明,FABP4与eGFR呈独立负相关(r=-0.211,P<0.001),与UACR无相关性(r=-0.047,P=0.534).(5)ROC曲线显示FABP4诊断DN的最佳截断值为103.9 μg/L,AUC为0.745(灵敏度51.2%,特异度92.7%).结论:T2DM患者血清FABP4水平升高与DN发生发展相关,有可能作为DN早期诊断的生物标志物.
Objective:To explore the association of fatty acid-binding protein 4(FABP4)with type 2 diabetic nephropathy(DN)and the value of FABP4 for early diagnosis of DN.Methods:218 type 2 diabetic mellitus(T2DM)patients and 20 healthy controls(control group)were recruited.The general clinical and anthropometric information of participants,such as height,weight,waist circumference,duration of diabetes were recorded at baseline,and calculate BMI.Plasma glucose,glycosylated hemoglobin,fasting insulin and C-peptide,liver and kidney function,blood lipids and other indicators were measured.Homeostasis model assessment-insulin resistance index(HOMA-IR)was calculated.Serum FABP4 levels were measured by ELISA.The glomerular filtration rate was estimated using a collaborative epidemiological equation for chronic kidney diseasa using a combination of serum creatinine(Scr)and cystatin C(Cys C).Urinary albumin to creatinine ratio(UACR)was calculated as the ratio of urinary albumin level to urinary creatinine level.According to estimated glomerular filtration rate(eGFR),all T2DM patients were divided into three subgroups:normal renal function group(eGFR ≥90 mUmin/1.73 m2),mild renal dysfunction group(60 mUmin/1.73 m2≤eGFR<90 mL/min/1.73 m2),and moderate renal dysfunction group(30 mL/min/1.73 m2≤eGFR<60 mL/min/1.73 m2).According to UACR,subgroups were:normal albuminuria group(UACR<30 mg/g),microalbuminuria group(30 mg/g≤UACR<300 mg/g),and macroalbuminuria group(UACR ≥300 mg/g).Multivariate regression analyses were employed to assess the correlation between FABP4 and eGFR and UACR.Results:(1)Comparing with the control group,serum FABP4 levels in T2DM patients were significantly higher.(2)Among three subgroups stratified according to eGFR,serum FABP4 levels increased significantly as eGFR decreased(P<0.001).No significant differences were observed among UACR subgroups(P=0.382).(3)Spearman correlation analysis showed that serum FABP4 was negatively correlated eGFR(r=-0.203,P=0.001),but not with UACR(r=0.130,P=0.055).(4)Multiple linear regression showed that FABP4 was negatively correlated with eGFR(r=-0.211,P<0.001),but not with UACR(r=-0.047,P=0.534).(5)The best cut-off value of FABP4 for diagnosing DN was 103.9 μg/L,the AUC was 0.745(sensitivity 51.2%,specificity 92.7%).Conclusion:The elevated serum FABP4 level in T2DM patients is associated with the development of DN.It may be used as a biomarker for early diagnosis of DN.

type 2 diabetes mellitusdiabetic nephropathyfatty acid-binding protein 4early diagnosisbiomarkers

赵小芹、黄萍、王鑫蕾、孙燚、王心薇、顾云娟

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南通大学附属医院内分泌科,江苏 226001

2型糖尿病 糖尿病肾病 脂肪酸结合蛋白4 早期诊断 生物标志物

江苏省研究型医院项目江苏省研究型医院项目

YJXYY202204-XKB09YJXY202204-YSB39

2024

南通大学学报(医学版)
南通大学

南通大学学报(医学版)

影响因子:0.637
ISSN:1674-7887
年,卷(期):2024.44(1)
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