【作者】 车志宏；

【导师】 周智广；

【作者基本信息】 中南大学 ， 内科学， 2008， 博士

【摘要】 目的:探讨新诊断代谢综合征患者脂联素水平的变化。实验设计:横断面、病例对照研究。方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清脂联素水平,研究代谢综合征及其相关疾病脂联素水平的变化。结果:①男性脂联素水平低于女性[4.44(0.97-16.55)vs.7.591.29-23.29)ug/ml,P<0.001]。校正BMI水平后这种差别仍然存在(P<0.001)。不同年龄研究对象脂联素水平没有差别。②校正年龄和性别后,血清脂联素水平与HDL-C、ANGPTL3水平正相关(P<0.05),与BMI、WC、WHR、体脂含量、FPG、TG、UA、FINS、HOMA-IR、hsCRP水平负相关(P<0.05)。校正年龄、性别和BMI后,血清脂联素仍与HDL-C、ANGPTL3水平正相关(P<0.05),与FPG、TG、UA、FINS、HOMA-IR负相关(P<0.05),与WC、WHR、体脂含量和hsCRP水平负相关消失。TG、ANGPTL3、性别和HOMA-IR,是血清脂联素水平的独立决定因素。③无论男性还是女性,高血压患者血清脂联素水平与对照组比较,无明显差别[(4.77(1.01-23.29) vs.5.17(0.97-22.27)ug/ml,P=0.991)]。④肥胖组、超重组脂联素水平低于体重正常组[4.34(1.61-15.09)vs.4.28(0.97-22.27)vs.5.99(1.16-23.29)ug/ml,P=0.001],而超重组和肥胖组之间没有差别。⑤校正年龄和性别后,高TG组与对照组脂联素水平低于对照组[4.40(0.97-23.29)vs.6.67(1.12-22.27)ug/ml,P=0.001)]。校正年龄和性别后,低HDL-C组低于对照组脂联素水平[4.96(0.97-14.88)vs.5.18(1.12-23.29)ug/ml,P=0.005)]。⑥校正年龄和性别后,糖耐量异常和正常糖耐量组的脂联素水平高于2型糖尿病[5.05(1.06-23.29)vs.5.50(0.97-22,27 vs.3.13(1.01-13.57)ug/ml,P<0.001)],而糖耐量正常组和糖耐量异常组无明显差别。⑦校正年龄和性别后高尿酸血症组脂联素低于对照组[3.9(1.20-13.72)vs.5.4(0.97-23.29)ug/ml,P=0.004]。⑧校正性别和年龄后,NAFLD组脂联素水平低于对照组[4.18(1.01-15.09)vs.6.3(0.97-23.29)ug/ml,P<0.001]。校正年龄、性别和BMI后这种差别仍然存在(P=0.013)。⑨校正年龄和性别后代谢综合征组脂联素浓度低于对照组[4.22(1.01-23.29 vs.5.41(0.97-22.27)ug/ml,P=0.002]。不同代谢综合征定义下的代谢综合征组的脂联素水平均低于其对照组。不同代谢综合征定义的代谢综合征组的脂联素水平无差别(P=0.909)。随着代谢异常数目的增加,脂联素水平降低(P=0.001)。从2个组分开始脂联素水平就开始降低。但是2个组分以上脂联素水平的不再降低。代谢综合征合并糖耐量异常或2型糖尿病脂联素水平低于未合并血糖异常者。高浓度脂联素组代谢综合征患病率低于低浓度脂联素组(P<0.001)。结论:除了高血压,代谢综合征及其组分脂联素水平降低;高尿酸血症者脂联素水平降低。NAFLD脂联素水平降低。目的:探讨新诊断代谢综合征患者血管生成素样蛋白3(ANGPTL3)水平的变化。设计:横断面、病例对照研究方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清ANGPTL3水平,研究代谢综合征及其相关疾病ANGPTL3水平的变化。结果:①男性和女性ANGPTL3水平没有差别(418.84±140.90 vs.437.22±160.46 ng/ml,P=0.384)。男性<50岁ANGPTL3水平低于>50岁者(p=0.009),校正BMI水平后这种差别仍然存在。女性不同年龄研究对象ANGPTL3水平没有差别。②校正年龄和性别后,血清ANGPTL3水平与脂联素水平正相关(P<0.001),与FINS、HOMAIR水平负相关(P=0.026和P=0.015)。校正年龄、性别和BMI后,血清ANGPTL3水平仍与脂联素水平正相关(P<0.001),与LDL-C水平正相关(P=0.049),但与FINS、HOMAIR水平负相关消失(P=0.118和P=0.0861。脂联素是血清ANGPTL3的独立决定因素。③校正年龄和性别后高血压患者血清ANGPTL3水平与对照组无差别(423.96±143.17 vs.421.24±153.72 ng/ml,P=0.894)。④校正年龄和性别后正常组、超重组、肥胖组三组间ANGPTL3水平有差异(453.51±145.28 vs.380.47±127.80 vs.450.73±161.37 ng/ml,P<0.001)。肥胖组、体重正常组高于超重组,但正常体重组和肥胖组之间没有差别;校正年龄、性别和脂联素后三组ANGPTL3水平仍有差别(F=5.572,P=0.004)。⑤校正年龄和性别后,高TG组与对照组ANGPTL3水平(424.69±154.06 vs.421.92±138.16 ng/ml,P=0.878)无差别。校正年龄和性别后,低HDL-C组与对照组ANGPTL3水平(428.46±134.06 vs.416.94±158.81 ng/ml,P=0.531)无差别。⑥2型糖尿病、糖耐量异常和正常糖耐量组ANGPTL3水平无差别。⑦高尿酸血症组与对照组ANGPTL3水平没有差别(428.48±144.52 vs.409.09±138.0ng/ml,P=0.374)。⑧NAFLD组ANGPTL3水平与对照组无差别(414.19±143.67 vs.435.41±144.58 ng/ml,P=0.256)。⑨代谢综合征组ANGPTL3水平与对照组相比,无差别(418.81±148.45 vs.426.49±144.10 ng/ml,P=0.674)。结论:血清ANGPTL3与脂联素水平独立正相关,而与TG和HDL-C无关,血清脂联素水平是ANGPTL3的独立决定因素。超重者ANGPTL3水平降低。目的:探讨新诊断代谢综合征患者血清视黄醇结合蛋白4水平的变化。方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫法反应测定血清视黄醇结合蛋白4(RBP4)水平,研究代谢综合征及其相关疾病RBP4水平的变化。结果:①男性RBP4水平高于女性(54.11±17.08 vs.38.72±12.46ug/ml,P<0.001);②校正年龄和性别后,血清RBP4水平与BMI、腰围、WHR、PBG,TG,CHOL、LDL、SBP、DBP、FINS、HOMA-IR、脂肪百分比和尿酸正相关(P<0.05),与HDL-C水平负相关(P=0.012);⑧TG、性别(男性=1,女性=2)、DBP、尿酸是血清RBP4的独立决定因素;④高四分位胰岛素抵抗者RBP4水平高于低四分位者(P=0.029);⑤男性高血压者RBP4水平高于无高血压者(61.96±19.16vs.51.28±15.38 ug/ml,P<0.001),女性高血压患者血清RBP4水平与对照组比较,无差别(P=0.551);校正年龄和性别后,超重组和肥胖组RBP4水平均高于体重正常组(45.75±16.11 vs.52.45±17.79 vs。55.60±16.94 ug/ml,P=0.026),但是超重组和肥胖组之间没有差别(P=0.274);校正年龄和性别后,高TG组RBP4水平高于对照组(55.22±17.72 vs.45.21±17.72 ug/ml,P<0.001);2型糖尿病组RBP4水平与糖耐量正常组、糖耐量异常组无差别(50.10±20.04 vs.48.38±14.67vs.53.96±19.23 ug/ml,P=0.074);⑥校正年龄和性别后高尿酸血症组RBP4浓度高于对照组(57.62±15.69 vs.48.43±16.88 ug/ml,P=0.032);⑦校正年龄和性别后,NAFLD组RBP4水平高于对照组(55.22±17.99 vs.47.44±15.24ug/ml,P=0.019);⑧校正年龄和性别后,代谢综合征组的RBP4水平高于对照组(54.79±18.32 vs.47.23±15.96ug/ml,P=0.002);随着代谢异常数目的增加,RBP4水平增加(P<0.001);高浓度RBP4组代谢综合征患病率高于低浓度组(P=0.002)。结论:RBP4与肥胖和代谢综合征相关,TG、性别、DBP和尿酸是血清RBP4的独立决定因素。高尿酸血症、非酒精性脂肪性肝病RBP4水平升高。目的:探讨新诊断代谢综合征患者血清中性粒细胞明胶酶相关脂笼蛋白2水平的变化。设计:横断面、病例对照研究方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清中性粒细胞明胶酶相关脂笼蛋白(LCN2)水平,研究代谢综合征及其相关疾病LCN2水平的变化。结果:①男性和女性LCN2水平没有差别[30.37(9.25-123.25 vs.26.37(9.75-82.5)ug/L,P=0.541]。不同年龄研究对象LCN2水平没有差别。②校正年龄和性别后,血清LCN2水平与BMI、腰围、体脂含量、hsCRP正相关(P<0.05),与HDL-C水平负相关(P=0.001)。校正年龄、性别和BMI后,血清LCN2水平与hsCRP正相关(P<0.05),与HDL-C水平负相关(P=0.023)。但是与腰围、体脂含量的正相关消失。HDL-C和hsCRP是血清LCN2的独立相关因素。③高血压患者血清LCN2水平与对照组无差别[29.25(10.75-123.25) vs.28(9.25-92.25)ug/L,P=0.741]。④正常组、超重组和肥胖组三组间LCN2水平有差异[29.0(10.75-82.50) vs. 26.75(9.25-86.5) vs.36.37(13-123.25)ug/L,P=0.018]。肥胖组LCN2水平高于正常体重组和超重组,但正常体重组和超重组之间没有差别。校正hsCRP、HDL-C水平后三个不同BMI组别之间LCN2水平仍有差异(P=0.046)。⑤校正年龄和性别后,高TG组与对照组LCN2水平无差别[29.0(10.75-86.5)vs.29.0(9.25-123.25)ug/L;P=0.676]。校正年龄和性别后,低HDL-C组LCN2水平高于对照组[32.62(9.75-82.50) vs.26.37(9.25-123.25)ug/L,P=0.001];校正BMI、hsCRP后,这种差别仍然存在(F=8.27,P=0.004)。⑥糖耐量正常、糖耐量异常和2型糖尿病组LCN2水平有差异[32.5(9.75-89.5) vs.32.25(9.25-92.25) vs.27.0(10.75-123.25)ug/L,P=0.008],2型糖尿病组LCN2水平高于糖耐量正常组(P=0.024),糖耐量异常组高于糖耐量正常组(P=0.006),但是其水平在2型糖尿病组与糖耐量异常组无差别(P=0.945)。校正年龄和性别后三组比较F=4.29,P=0.015;校正年龄、性别、BMI后三组比较F=2.876,P=0.058。⑦高尿酸血症组与对照组LCN2水平无差别[29.12(9.25-130.25) vs.30(13-123.25)ug/L,P=0.247]。⑧NAFLD组LCN2水平与对照组无差别[32.37(9.25-130.25)vs.28.37(10.75-123.25)ug/L,P=0.134]。⑨校正年龄和性别后代谢综合征组LCN2水平高于对照组[32.37(9.25-156.5)vs.28(10.75-118.25)ug/L,P=0.032]。不同代谢综合征定义下的代谢综合征组的LCN2水平均高于其对照组。不同代谢综合征定义的代谢综合征组的LCN2水平无差别(P=0.987)。随着代谢异常数目的增加,LCN2水平增加没有达到统计学意义(校正年龄性别后, F=1.891,P=0.096)。随着LCN2浓度增加,代谢综合征患病率增加没有达到统计学意义(P=0.081)。结论:血清LCN2水平与hsCRP独立正相关,可以作为新的与肥胖和代谢综合征相关的炎症指标。低HDL-C血症者、2型糖尿病、糖耐量异常者、肥胖者与对照组比较,LCN2水平升高。代谢综合征患者LCN2水平升高。更多还原

【Abstract】 Object: To evaluate serum adiponectin distribution and its association with metabolic syndrome.Design: Cross-sectional and case control study.Methods: 111 MetS cases and 152 controls were measured serum adiponectin levels with sandwich ELISA.Results:①Serum adiponectin levels in men were significantly lower than those in women [4.44(0.97-16.55) vs. 7.59(1.29-23.29) ug/ml, P<0.001].The difference did not disappear after adjusted for BMI (P<0.001). No age-associated difference in serum adiponectin levels was observed.②Serum adiponectin concentrations were positively correlated with HDL-C and ANGPTL3 (P<0.05) after adjusted for age and sex. Serum adiponectin concentrations were negatively correlated with BMI, WC, WHR, fat percentage, FPG,TG,UA, FINS, HOMAIR, and hsCRP (P<0.05). TG, ANGPTL3, sex, and HOMA-IR were found to be independent determinants for serum adiponectin concentrations.③No difference in serum adiponectin levels was observed between the hypertension and the control group [(4.77(1.01-23.29) vs. 5.17(0.97-22.27) ug/ml, P=0.991)].④Serum adiponectin concentrations were lower in the obesity and overweight groups than in the lean group [4.34(1.61-15.09) vs. 4.28(0.97-22.27) vs. 5.99(1.16-23.29) ug/ml , P=0.001]. No difference in serum adiponectin levels was observed between the overweight and the obesity group.⑤Serum adiponectin concentrations were significantly lower in the hypertriglyceridemia than in the control group [4.40(0.97-23.29) vs. 6.67(1.12-22.27) ug/ml, P=0.001)]. Serum adiponectin concentrations were significantly lower in the hypo-high density lipoproteinemia than in the control group [4.96(0.97-14.88) vs. 5.18(1.12-23.29) ug/ml, P=0.005)].⑥Serum adiponectin concentrations were significantly lower in the T2DM than in the NGT and IGT groups [5.05(1.06-23.29) vs. 5.50(0.97-22.27) vs. 3.13(1.01-13.57) ug/ml, P<0.001]. No difference in serum adiponectin levels was observed between the NGT and the IGT groups.⑦Serum adiponectin concentrations were significantly lower in the hyperuricemia than in the control group [3.9(1.20-13.72) vs. 5.4(0.97-23.29) ug/ml, P=0.004].⑧Serum adiponectin concentrations were significantly lower in the NAFLD than in the control group [4.18(1.01-15.09) vs. 6.3(0.97-23.29) ug/ml, P<0.001].⑨Serum adiponectin concentrations were significantly lower in the metabolic syndrome than in the control group [4.22(1.01-23.29) vs. 5.41(0.97-22.27) ug/ml, P=0.002]. Serum adiponectin concentrations were all significantly lower in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There were no differences in adiponectin levels among metabolic syndrome groups by different definitions (P=0.909) . Serum adiponectin concentrations were significantly lower with more metabolic disorders. In the highest adiponectin tertile, the MetS risk was significantly lower than in the lowest tertile.Conclusion: Each component of metabolic syndrome, except for blood pressure, showed significantly lower serum adiponectin concentrations for both men and women. Serum circulating adiponectin concentrations are decreased in human subjects with hyperuricemia. Object: To evaluate serum angiopoietin -like protein 3 (ANGFTL3) distributions and its association with metabolic syndrome.Design: Cross-sectional and case control study.Methods: 111 MetS cases and 152 controls were measured serum ANGPTL3 levels with sandwich ELISA.Results:①No gender-associated difference in serum ANGPTL3 levels was observed(418.84±140.90 vs. 437.22±160.46 ng/ml, P=0.384). Serum ANGPTL3 levels in men > 50 years were significantly higher than those <50 years.②Serum ANGPTL3 concentrations were positively correlated with adiponectin (P<0.05) after adjusted for age and sex. Serum ANGPTL3 concentrations were negatively correlated with FINS and HOMA-IR (P<0.05). Adiponectin was found to be independent determinant for serum ANGPTL3 concentrations.③No difference in serum ANGPTL3 levels was observed between the hypertension and the control group (423.96±143.17 vs. 421.24±153.72 ng/ml, P=0.894).④Serum ANGPTL3 concentrations were lower in the overweight group than in the lean and obesity group (453.51±145.28 vs. 380.47±127.80 vs. 450.73±161.37ng/ml,P<0.001).⑤Serum ANGPTL3 concentrations were no significantly difference between hypertriglyceridemia and control group (424.69±154.06 vs. 421.92±138.16ng/ml, P=0.878). No difference in serum ANGPTL3 levels was observed between the hypo-high density lipoproteinemia and the control group (428.46±134.06 vs. 416.94±158.81 ng/ml, P=0.531).⑥No difference in serum ANGPTL3 levels was observed among NGT, IGT and T2DM groups.⑦No difference in serum ANGPTL3 levels was observed between the hyperuricemia and the control group (428.48±144.52 vs. 409.09±138.0ng/ml, P=0.374).⑧No difference in serum ANGPTL3 levels was observed between the NAFLD and the control group (414.19±143.67 vs. 435.41±144.58 ng/ml, P=0.256).⑨No difference in serum ANGPTL3 levels was observed between the metabolic syndrome and the control group (418.81±148.45 vs. 426.49±144.10 ng/ml, P=0.674).Conclusions: Serum ANGPTL3 concentrations were independently positively correlated with adiponectin, but not correlated with TG and HDL-C. Object: To evaluate serum Retinol-binding protein 4 (RBP4) distributions and its association with metabolic syndrome.Design: Cross-sectional and case control study.Methods: 111 MetS cases and 152 controls were measured serum RBP4 levels with sandwich ELISA.Results:①Serum RBP4 levels in men were significantly higher than those in women (54.11±17.08 vs. 38.72±12.46 ug/ml, P<0.001). No age-associated difference in serum RBP4 levels was observed.②Serum RBP4 concentrations were positively correlated with BMI, WC, WHR, PBG,TG,CHOL, LDL, SBP, DBP, FINS, HOMA-IR, fat percentage and UA(P<0.05)after adjusted for sex and age. Serum RBP4 concentrations were negatively correlated with HDL-C (P<0.05). TG,sex(male=1, female=2), DBP and UA were found to be independent determinants for serum RBP4 concentrations.③Serum RBP4 concentrations were higher in the hypertension in men than the control group [61.96±19.16 vs. 51.28±15.38ug/ml, P<0.001].④Serum RBP4 concentrations were higher in the obesity and overweight groups than in the lean group (45.75±16.11 vs. 52.45±17.79 vs. 55.60±16.94ug/ml, P=0.026). No difference in serum RBP4 levels was observed between the overweight and the obesity group (P=0.274).⑤No difference in serum RBP4 levels was observed among the NGT, IGT and T2DM groups (50.10±20.04 vs. 48.38±14.67 vs. 53.96±19.23ug/ml, P=0.074).⑥Serum RBP4 concentrations were significantly higher in the hypertriglyceridemia than in the control group (55.22±17.72 vs. 45.21±17.72ug/ml, P<0.001).⑦Serum RBP4 concentrations were significantly higher in the hyperuricemia than in the control group (57.62±15.69 vs.48.43±16.88, P=0.032).⑧Serum RBP4 concentrations were significantly higher in the NAFLD than in the control group (55.22±17.99 vs. 47.44±15.24ug/ml, P=0.019).⑨Serum RBP4 concentrations were significantly higher in the_metabolic syndrome than in the control group (54.79±18.32 vs. 47.23±15.96 ug/ml , P=0.002). Serum RBP4 concentrations were all significantly higher in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There was no difference in RBP4 levels among metabolic syndrome groups by different definitions. Serum RBP4 concentrations were significantly higher with more metabolic disorders. In the highest RBP4 tertile, the MetS risk was significantly higher than in the lowesttertile.Conclusion: Each component of metabolic syndrome, except forblood glucose, showed significantly higher serum RBP4 concentrations for both men and women.serum circulating RBP4 concentrations are elevated in human subjects with hyperuricemia. Serum circulating RBP4 concentrations are elevated in human subjects with NAFLD. Object: To evaluate serum lipocalin 2 (LCN2) distributions and its association with metabolic syndrome.Design: Cross-sectional and case control study.Methods: 111 MetS cases and 152 controls were measured serum LCN2 levels with sandwich ELISA.Results:①No gender, sex-associated difference in serum LCN2 levels was observed.②Serum LCN2 concentrations were positively correlated with BMI, WC, fat percentage, and hsCRP (P<0.05) after adjusted for sex and age. Serum LCN2 concentrations were negatively correlated with HDL-C (P<0.05). HDL-C and hsCRP were found to be independent determinants for serum LCN2 concentrations.③No difference in serum LCN2 levels was observed between the hypertension and the control group [29.25(10.75-123.25) vs. 28(9.25-92.25) ug/L, P=0.741].④Serum LCN2 concentrations were higher in the obesity group than in the lean and overweight groups [36.37(13-123.25) vs. 29.0(10.75-82.50) vs. 26.75(9.25-86.5) ug/L, P=0.018]. No difference in serum LCN2 levels was observed between the overweight and the lean groups.⑤Serum LCN2 concentrations were no significantly difference between hypertriglyceridemia and control group [29.0(10.75-86.5) vs. 29.0(9.25-123.25)ug/L, P=0.676]. Serum LCN2 concentrations were significantly higher in the hypo-high density lipoproteinemia than the control group [32.62(9.75-82.50) vs. 26.37(9.25-123.25), P=0.001].⑥Serum LCN2 concentrations were higher in the IGT and T2DM groups than in the NGT group [32.5(9.75-89.5) vs. 32.25(9.25-92.25) vs. 27.0(10.75-123.25)ug/L, P=0.008].⑦No difference in serum LCN2 levels was observed between the hyperuricemia and the control group [29.12(9.25-130.25) vs. 30(13-123.25)ug/L, P=0.247].⑧No difference in serum ANGPTL3 levels was observed between the NAFLD and the control group [32.37(9.25-130.25) vs. 28.37(10.75-123.25)ug/L , P=0.134].⑨Serum LCN2 concentrations were significantly higher in the metabolic syndrome than in the control group [32.37(9.25-156.5) vs. 28(10.75-118.25) ug/L, P=0.032]. Serum LCN2 concentrations were all significantly higher in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There was no difference in LCN2 levels among metabolic syndrome groups by different definitions.Conclusion: Serum LCN2 concentrations were higher in obesity, T2DM, and metabolic syndrome. Serum lipocalin-2 is independently positively correlated with hsCRP, and can be a useful new marker for evaluating inflammatory status in obesity and MetS.更多还原