视黄醇结合蛋白4与糖脂代谢指标及胆汁胆固醇饱和指数之间的相关性

Correlation of retinol binding protein 4 with metabolic indexes of glucose and lipid, bile cholesterol saturation index

目的:探讨血清及胆汁中视黄醇结合蛋白4(retinol binding protein 4,RBP4)的浓度与胰岛素抵抗、血脂异常、胆汁胆固醇饱和指数(cholesterol saturation index,CSI)之间的关系。方法:将住院手术治疗胆囊结石的患者随机分为糖尿病组和对照组,每组30例。采用ELISA法检测糖尿病组和对照组血清及胆汁中RBP4的浓度,酶比色法测定胆汁胆固醇、胆汁酸和磷脂的含量,采用Carey表计算胆汁CSI,分析血清及胆汁中RBP4水平与各项指标的相关性,并对相关指标进行多元线性回归分析。结果:糖尿病组血清及胆汁中RBP4的浓度均显著高于对照组(均P<0.01)。两组血清总胆汁酸(total bile acid,TBA),TG,HDL,以及胆汁TBA,TC,磷脂及CSI之间的差异均无统计学意义(均P>0.05)。糖尿病组血清TC,LDL,空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)以及稳态模型评估的胰岛素抵抗指数(homeostasis model assessment for insulin resistance index,HOMA-IR)均高于对照组,差异均有统计学意义(均P<0.05)。校正年龄影响后的偏相关分析表明:胆汁RBP4与体质量指数(body mass index,BMI),腰围(waist circumference,WC),空腹血清胰岛素(fast serum insulin,FINS),FBG,TC,LDL,HOMA-IR呈正相关(分别r=0.283,0.405,0.685,0.667,0.553,0.424,0.735);血清RBP4与WC,FINS,FBG,TC,LDL,HOMA-IR呈正相关(分别r=0.317,0.734,0.609,0.528,0.386,0.751);逐步法多元线性回归分析表明HOMA-IR,BMI,WC与胆汁RBP4水平独立相关(回归方程如下:Y胆汁RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813);HOMA-IR,WC与血清RBP4水平独立相关(回归方程如下:Y血清RBP4=2.832XHOMA-IR+0.235XWC-20.128),HOMA-IR与RBP4的相关性最强。结论:糖尿病组血清及胆汁中RBP4的浓度显著高于对照组;HOMA-IR,BMI,WC与胆汁RBP4呈独立相关;HOMA-IR,WC与血清RBP4呈独立相关;HOMA-IR与RBP4的相关性最强。RBP4可能在2型糖尿病合并胆囊结石的发展过程中起着重要作用。

Objective: To measure retinol binding protein 4(RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index(CSI). Methods: A total of 60 patients with gallstone were divided into a diabetes group(n=30) and a control group(n=30). The concentrations of RBP4 in serum and bile were detected by enzymelinked immunosorbent assay(ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.Results: The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group(both P<0.01). There was no significant difference in the serum total bile acid(TBA), serum triglyceride(TG), serum high-density lipoprotein(HDL), bile TBA, bile total cholesterol(TC), bile phospholipids and bile CSI between the 2 groups(all P>0.05); but the serum TC, low density lipoprotein(LDL), fasting blood glucose(FBG), fasting insulin(FINS), and homeostasis model assessment for insulin resistance(HOMAIR) in the diabetes group were significantly increased compared to those in the control group(all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index(BMI), waist circumference(WC), FINS, FBG, TC, LDL and HOMA-IR(r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR(r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4(multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently(multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations showed that HOMA-IR was the strongest correlation factor with RBP4.Conclusion: RBP4 concentrations in serum and bile in the diabetes group are significantly higher than those in the control group. HOMA-IR, BMI and WC are independently correlated with the level of bile RBP4. HOMA-IR and WC are independently correlated with the serum RBP4 level. HOMA-IR is the strongest correlation factor with RBP4. RBP4 might play an important role in the course of gallstone formation in Type 2 diabetes mellitus.