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糖尿病肾病(DN)是糖尿病(DM)最常见的微血管并发症,发病机制与长期持续高血糖、胰岛素抵抗(IR)、脂代谢紊乱、炎症因子、衰老等因素密切相关[1-2]。DN病情隐匿,一旦进入临床蛋白尿期病情难以控制,但DN的早期肾脏形态和功能变化是可以逆转的,是否可以寻找一种新的临床指标,有助于临床早期诊断DN而逆转肾功能?Betotraphin是一种新发现的肝源性激素,研究[3-5]表明它参与了葡萄糖和脂质代谢;用S961治疗的小鼠通过过表达betatrophin[6]可引起IR,说明它与IR亦存在关联。先前EBERT等[7-8]研究显示betatrophin水平与肾功能相关。台湾研究者CHEN等[9]也首次发现betatrophin可能是一种新的内分泌调节因子,参与了DN的发展。目前国内研究betatrophin与DN的相关报道较少,此次研究通过对DN不同蛋白尿期的betatrophin测定,分析betatrophin与2型DN相关性,旨在为DN的早期诊断提供理论依据。
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与对照组比较,正常白蛋白尿组betatrophin、收缩压(SBP)、舒张压(DBP)、FPG、FIns、HOMA-IR、糖化血红蛋白(HbA1c)、TG、LDL-C明显升高(P < 0.05),年龄、体质量指数(BMI)、FCP、TC、HDL-C、eGFR差异无统计学意义(P>0.05);微量白蛋白尿组betatrophin、SBP、DBP、FPG、FIns、HOMA-IR、HbA1c、FCP、TG、TC、LDL-C明显升高(P < 0.05),年龄、BMI、HDL-C、eGFR差异无统计学意义(P>0.05);大量白蛋白尿组betatrophin、SBP、DBP、FPG、FIns、HOMA-IR、HbA1c、FCP、TG、TC明显升高,eGFR降低(P < 0.05),年龄、BMI、LDL-C、HDL-C差异无统计学意义(P>0.05)(见表 1)。
指标 对照组(n=45) 正常蛋白尿组(n=30) 微量蛋白尿组(n=33) 大量蛋白尿组(n=19) F P MS组内 性别/(男/女) 22/23 15/15 19/14 9/10 — — — 年龄/岁 52.16±8.78 53.43±8.34 52.70±10.81 54.30±9.63 0.34 >0.05 90.331 SBP/mmHg 118.07±9.71 130.53±11.64△ 130±14.25△ 127.96±16.29△ 8.70 < 0.01 161.859 DBP/mmHg 78.29±6.06 86.80±8.72△ 83.94±8.37△ 85.09±9.75△ 8.59 < 0.01 64.036 BMI/(kg/m2) 24.94±2.11 25.63±3.29 25.99±3.07 25.94±3.56 1.49 >0.05 8.432 FPG/(mmol/L) 5.11±0.43 8.86±4.44△ 10.65±3.31△ 12.51±5.80△※ 28.08 < 0.01 12.904 UACR/(mg/g) 12.98±6.04 13.00±5.14 111.21±61.99△* 407.39±182.56△*# 465.14 < 0.01 2 364.351 betatrophin/(pg/mL) 312.43±119.73 829.56±180.65△ 903.44±152.55△ 930.85±199.12△* 139.26 < 0.01 23 970.950 TG/(mmol/L) 1.00±0.33 2.08±1.33△ 2.16±1.08△ 2.88±2.22△ 14.58 < 0.01 1.557 TC/(mmol/L) 4.57±0.64 4.90±1.13 5.19±1.12△ 5.06±1.09△ 3.18 < 0.05 0.969 HDL-C/(mmol/L) 1.73±0.44 1.57±0.53 1.53±0.42 1.62±0.51 1.76 >0.05 0.210 LDL-C/(mmol/L) 2.31±0.56 2.85±0.93△ 2.97±1.06△ 2.41±1.18*# 5.42 < 0.01 0.799 eGFR/(mL/min) 109.80±19.22 103.98±24.47 102.54±24.71 94.16±20.87△ 2.31 >0.05 500.134 FIns/(uIU/mL) 4.82(4.29,5.44) 7.53(6.32,9.33)△ 7.94(6.34,13.09)△ 10.79(7.25, 13.89)△* — — — HOMA-IR 1.08(0.96,1.22) 2.76(2.07,3.74)△ 3.50(2.85,7.50)△* 5.26(3.53, 7.91)△* — — — HbA1c/% 5.26±0.92 9.09±2.05△ 8.82±2.13△ 8.46±1.97△ 43.03 < 0.01 3.031 FCP/(ng/mL) 1.76±0.35 1.82±0.91 2.40±1.55△ 2.47±0.96△* 4.44 < 0.05 1.016 Cr/(μmol/L) 63.40±13.30 61.13±12.24 65.85±16.57 69.83±13.42* 1.82 >0.05 192.978 与正常组比较△P < 0.05;与正常蛋白组比较*P < 0.05;与微量蛋白组比较#P < 0.05 表 1 一般资料及实验室检测指标比较[x±s;M(P25, P75)]
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与正常白蛋白尿组比较,微量白蛋白尿组HOMA-IR明显升高(P < 0.05),其余各指标差异无统计学意义(P>0.05)。与正常白蛋白尿组比较,大量白蛋白尿组betatrophin、FPG、FIns、HOMA-IR、FCP、LDL-C、Cr明显增高(P < 0.05),SBP、DBP、BMI、TG、TC、HDL-C、HbA1c差异无统计学意义(P>0.05)。与微量白蛋白尿组比较,大量蛋白尿组LDL-C明显升高(P < 0.05),其余各指标差异无统计学意义(P>0.05)(见表 1)。
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T2DM病人血清betatrophin水平与TG、FPG、HOMA-IR、UACR水平呈正相关(P < 0.01);UACR值与betatrophin、FPG、TG、HOMA-IR呈正相关(P < 0.05~P < 0.01),与eGFR呈负相关(P < 0.05)(见表 2)。
变量 UACR betatrophin 变量 UACR betatrophin 年龄 0.093 0.053 FPG 0.349** 0.287 SBP -0.071 -0.055 FIns 0.131 0.164 DBP -0.031 -0.069 HDMA-IR 0.284** 0.292** BMI 0.031 0.204 HbA1c 0.044 0.075 UACR - 0.319** FCP 0.144 0.077 GFR -0.223* 0.162 TC 0.137 0.124 betatrophin 0.319 - HDL-C 0.045 -0.149 TG 3.242* 0.425** LDL-C -0.182 0.078 注:*P < 0.05,**P < 0.01 表 2 T2DM病人betatrophin、UACR与临床各指标的相关性分析(r)
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以UACR为因变量,TG、FPG、LDL-C、HDL-C、betatrophin、FIns、HOMA-IR、HbA1c、FCP为自变量进行多元逐步回归分析,结果显示betatrophin、LDL-C是影响UACR的独立危险因素;回归方程为Y=-157.38+0.25×betatrophin -42.91×LDL-C (P < 0.05)。以betatrophin为因变量,UACR、TG、FPG、LDL-C、HDL-C、FIns、HOMA-IR、HbA1c、FCP为自变量进行多元逐步回归分析,结果显示UACR、TG是影响betatrophin的独立危险因素;回归方程为Y=568.18+0.23×UAER+41.82×TG (P < 0.05) (见表 3~4)。
自变量 B SE β t P 常量 -157.383 282.476 — -0.56 >0.05 TG 17.177 14.456 0.142 1.19 >0.05 FPG 6.456 9.051 0.159 0.71 >0.05 LDL-C -42.906 19.008 -0.239 -2.26 < 0.05 betatrophin 0.248 0.123 0.231 2.02 < 0.05 FIns -4.143 7.145 -0.194 -0.58 >0.05 HOMA-IR 10.056 15.706 0.251 0.64 >0.05 HbA1c 0.358 10.348 0.004 0.04 >0.05 FCP 14.839 20.613 0.097 0.72 >0.05 TC 33.505 18.445 0.196 1.82 >0.05 HDL-C 49.955 41.113 0.123 1.22 >0.05 Cr 1.527 2.013 0.116 0.76 >0.05 BMI -3.689 6.936 -0.063 -0.53 >0.05 表 3 T2DM病人中UACR的多元线性回归分析
自变量 B SE β t P 常量 568.178 263.055 — 2.16 < 0.05 TG 41.824 13.079 0.371 3.20 < 0.01 FPG 2.607 8.720 0.069 0.30 >0.05 LDL-C 35.721 18.426 0.214 1.94 >0.05 UACR 0.228 0.113 0.245 2.02 < 0.05 FIns -2.304 6.874 -0.116 -0.34 >0.05 HOMA-IR 7.923 15.100 0.212 0.53 >0.05 HbA1c -1.258 9.938 -0.014 -0.13 >0.05 FCP -1.516 19.872 -0.011 -0.08 >0.05 TC -14.611 18.054 -0.092 -0.81 >0.05 HDL-C -19.458 39.845 -0.052 -0.49 >0.05 Cr 0.467 1.941 0.038 0.24 >0.05 BMI 0.239 6.675 0.004 0.04 >0.05 表 4 T2DM病人中betatrophin的多元线性回归分析
血清betatrophin水平与2型糖尿病肾病的相关性研究
Correlation between serum betatrophin level and type 2 diabetic nephropathy
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摘要:
目的探讨血清betatrophin水平在2型糖尿病肾病病人的临床价值。 方法选取45名健康体检者为对照组,82例门诊及住院2型糖尿病(T2DM)病人为T2DM组。T2DM组分为3组:正常白蛋白尿组[尿白蛋白肌酐比(UACR) < 30 mg/g],微量白蛋白尿组(UACR 30~300 mg/g)和大量白蛋白尿组(UACR>300 mg/g);采用酶联免疫吸附法测定血清betatrophin水平,同时检测血糖、血脂等指标。 结果T2DM病人各组的betatrophin、空腹血糖(FPG)、空腹胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR)、糖化血红蛋白(HbA1c)、三酰甘油(TG)均明显高于对照组,且大量蛋白尿组betatrophin、FPG、FIns、HOMA-IR、C肽(FCP)明显高于正常白蛋白尿组(P < 0.05)。T2DM组的betatrophin水平与TG(r=0.425)、UACR(r=0.319)、FPG(r=0.287)、HOMA-IR(r=0.292)显著正相关(P < 0.01)。多元逐步回归分析显示betatrophin、低密度脂蛋白胆固醇是影响UACR的独立危险因素;UACR、TG是影响betatrophin的独立危险因素。 结论血清betatrophin水平在2型糖尿病肾病病人中显著升高,随着病情加重,betatrophin水平也逐渐升高,提示betatrophin可能参与了糖尿病肾病的发生发展。 -
关键词:
- 2型糖尿病肾病 /
- betatrophin /
- 尿白蛋白肌酐比值
Abstract:ObjectiveTo explore the clinical value of serum betatrophin level in patients with type 2 diabetic nephropathy. MethodsA total of 45 healthy outpatients were enrolled as the control group.Eighty-two patients with T2DM were set as the T2DM group, and were subdivided into the normal albuminuria group [urinary albumin creatinine ratio(UACR) < 30 mg/g], microalbuminuria group(UACR at 30-300 mg/g) and macroalbuminuria group(UACR>300 mg/g).The serum level of betatrophin was measured using enzyme linked immunosorbent assay, and the levels of blood glucose and blood lipid were measured simultaneously. ResultsThe levels of betatrophin, FPG, FIns, HOMA-IR, HbA1c and TG in T2DM group were significantly higher than those in control group(P < 0.05), and the levels of betatrophin, FPG, FIns, HOMA-IR and FCP in macroalbuminuria group were significantly higher than those in normal albuminuria group(P < 0.05).The serum level of betatrophin in T2DM patients was positively correlated with the TG(r=0.425), FPG(r=0.287), UACR(r=0.319) and HOMA-IR(r=0.292) (P < 0.01).The results of stepwise multiple regression analysis showed that betatrophin and LDL-C were the independent relevant factors affecting UACR, and the UACR and TG were the independent relevant factors affecting betatrophin level. ConclusionsThe serum level of betatrophin in patients with type 2 diabetic nephropathy increases significantly, and gradually increases with the aggravation of the disease, which suggest that betatrophin may be involved in the occurrence and development of diabetic nephropathy. -
表 1 一般资料及实验室检测指标比较[x±s;M(P25, P75)]
指标 对照组(n=45) 正常蛋白尿组(n=30) 微量蛋白尿组(n=33) 大量蛋白尿组(n=19) F P MS组内 性别/(男/女) 22/23 15/15 19/14 9/10 — — — 年龄/岁 52.16±8.78 53.43±8.34 52.70±10.81 54.30±9.63 0.34 >0.05 90.331 SBP/mmHg 118.07±9.71 130.53±11.64△ 130±14.25△ 127.96±16.29△ 8.70 < 0.01 161.859 DBP/mmHg 78.29±6.06 86.80±8.72△ 83.94±8.37△ 85.09±9.75△ 8.59 < 0.01 64.036 BMI/(kg/m2) 24.94±2.11 25.63±3.29 25.99±3.07 25.94±3.56 1.49 >0.05 8.432 FPG/(mmol/L) 5.11±0.43 8.86±4.44△ 10.65±3.31△ 12.51±5.80△※ 28.08 < 0.01 12.904 UACR/(mg/g) 12.98±6.04 13.00±5.14 111.21±61.99△* 407.39±182.56△*# 465.14 < 0.01 2 364.351 betatrophin/(pg/mL) 312.43±119.73 829.56±180.65△ 903.44±152.55△ 930.85±199.12△* 139.26 < 0.01 23 970.950 TG/(mmol/L) 1.00±0.33 2.08±1.33△ 2.16±1.08△ 2.88±2.22△ 14.58 < 0.01 1.557 TC/(mmol/L) 4.57±0.64 4.90±1.13 5.19±1.12△ 5.06±1.09△ 3.18 < 0.05 0.969 HDL-C/(mmol/L) 1.73±0.44 1.57±0.53 1.53±0.42 1.62±0.51 1.76 >0.05 0.210 LDL-C/(mmol/L) 2.31±0.56 2.85±0.93△ 2.97±1.06△ 2.41±1.18*# 5.42 < 0.01 0.799 eGFR/(mL/min) 109.80±19.22 103.98±24.47 102.54±24.71 94.16±20.87△ 2.31 >0.05 500.134 FIns/(uIU/mL) 4.82(4.29,5.44) 7.53(6.32,9.33)△ 7.94(6.34,13.09)△ 10.79(7.25, 13.89)△* — — — HOMA-IR 1.08(0.96,1.22) 2.76(2.07,3.74)△ 3.50(2.85,7.50)△* 5.26(3.53, 7.91)△* — — — HbA1c/% 5.26±0.92 9.09±2.05△ 8.82±2.13△ 8.46±1.97△ 43.03 < 0.01 3.031 FCP/(ng/mL) 1.76±0.35 1.82±0.91 2.40±1.55△ 2.47±0.96△* 4.44 < 0.05 1.016 Cr/(μmol/L) 63.40±13.30 61.13±12.24 65.85±16.57 69.83±13.42* 1.82 >0.05 192.978 与正常组比较△P < 0.05;与正常蛋白组比较*P < 0.05;与微量蛋白组比较#P < 0.05 表 2 T2DM病人betatrophin、UACR与临床各指标的相关性分析(r)
变量 UACR betatrophin 变量 UACR betatrophin 年龄 0.093 0.053 FPG 0.349** 0.287 SBP -0.071 -0.055 FIns 0.131 0.164 DBP -0.031 -0.069 HDMA-IR 0.284** 0.292** BMI 0.031 0.204 HbA1c 0.044 0.075 UACR - 0.319** FCP 0.144 0.077 GFR -0.223* 0.162 TC 0.137 0.124 betatrophin 0.319 - HDL-C 0.045 -0.149 TG 3.242* 0.425** LDL-C -0.182 0.078 注:*P < 0.05,**P < 0.01 表 3 T2DM病人中UACR的多元线性回归分析
自变量 B SE β t P 常量 -157.383 282.476 — -0.56 >0.05 TG 17.177 14.456 0.142 1.19 >0.05 FPG 6.456 9.051 0.159 0.71 >0.05 LDL-C -42.906 19.008 -0.239 -2.26 < 0.05 betatrophin 0.248 0.123 0.231 2.02 < 0.05 FIns -4.143 7.145 -0.194 -0.58 >0.05 HOMA-IR 10.056 15.706 0.251 0.64 >0.05 HbA1c 0.358 10.348 0.004 0.04 >0.05 FCP 14.839 20.613 0.097 0.72 >0.05 TC 33.505 18.445 0.196 1.82 >0.05 HDL-C 49.955 41.113 0.123 1.22 >0.05 Cr 1.527 2.013 0.116 0.76 >0.05 BMI -3.689 6.936 -0.063 -0.53 >0.05 表 4 T2DM病人中betatrophin的多元线性回归分析
自变量 B SE β t P 常量 568.178 263.055 — 2.16 < 0.05 TG 41.824 13.079 0.371 3.20 < 0.01 FPG 2.607 8.720 0.069 0.30 >0.05 LDL-C 35.721 18.426 0.214 1.94 >0.05 UACR 0.228 0.113 0.245 2.02 < 0.05 FIns -2.304 6.874 -0.116 -0.34 >0.05 HOMA-IR 7.923 15.100 0.212 0.53 >0.05 HbA1c -1.258 9.938 -0.014 -0.13 >0.05 FCP -1.516 19.872 -0.011 -0.08 >0.05 TC -14.611 18.054 -0.092 -0.81 >0.05 HDL-C -19.458 39.845 -0.052 -0.49 >0.05 Cr 0.467 1.941 0.038 0.24 >0.05 BMI 0.239 6.675 0.004 0.04 >0.05 -
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