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Chinese Journal of Hepatology logoLink to Chinese Journal of Hepatology
. 2018 Jul 20;26(7):524–529. [Article in Chinese] doi: 10.3760/cma.j.issn.1007-3418.2018.07.009

非酒精性脂肪性肝病患者营养状态和能量代谢特点

Nutritional status and energy metabolism characteristics in patients with nonalcoholic fatty liver disease

Ye Qing 1, Liu Fang 1, Wang Xin 2, Han Tao 1,通信作者:, Qi Yumei 2, Wang Fengmei 1,
Editor: 金 生
PMCID: PMC12769346  PMID: 30317776

Abstract

Objective

To study the nutritional status and energy metabolic characteristics of patients with nonalcoholic fatty liver disease (NAFLD), and to provide evidence for clinical evaluation and intervention.

Methods

A total of 359 NAFLD patients diagnosed on ultrasound from June 2015 to March 2017 were selected as study subjects and divided into mild, moderate to severe fatty liver disease group and 50 healthy subjects as control group. The changes of ICW, ECW, body fat, skeletal muscle, protein and visceral fat area (VFA) of patients and controls were analyzed by using body composition analyzer. The energy metabolism index was measured by the oxidation rate of resting energy expenditure(REE), respiratory quotient (RQ), and the oxidation rates of the three nutrients (CHO %, FAT %, and PRO %). According to different types of data, non-parametric tests like Kruskal-Wallis or x2 were used for this analysis.

Results

Compared with the mild fatty liver group and the control group, the moderate and severe fatty liver group the BMI, waist circumference, waist-hip ratio were significantly elevated (P-value<0.001), and their serum alanine aminotransferase, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, FBS levels were significantly increased (P value<0.05). The Body composition analysis showed that there was no significant difference in skeletal muscle content between the three groups (P=0.067). The ICW, ECW, protein, body fat content of moderate and severe fatty liver group were significantly higher than those of mild fatty liver group and control group (P<0.01), but there was no significant difference between the mild fatty liver group and the control group. There was significant difference in the VFA between the three groups, while VFAin the moderate and severe fatty liver group was significantly increased. Metabolic results showed that the RQ of patients with moderate-severe fatty liver and mild fatty liver were 0.72±0.08 and 0.78±0.06, respectively, which were lower than those of the control group (0.80±0.02), P=0.004. Resting energy expenditure (REE) was not significantly different between moderate and severe fatty liver group and mild fatty liver group (P=0.207), but both were significantly higher than those of the control group (P<0.001). The percentages of CHO, FAT and PRO in moderate and severe fatty liver group were 19.49%±9.71%, 66.23%±12.54% and 14.22%±6.11% respectively. Compared with the control group, CHO % decreased, and FAT % increased.

Conclusion

NAFLD patients have different extent of nutritional imbalance and energy metabolism disorders, the use of Body Composition analyzer and metabolic cart can comprehensively assess and monitor NAFLD patient's nutrition and energy metabolism status, to provide a basis for clinical intervention.

Keywords: Nonalcoholic fatty liver disease, Bioelectric impedance analysis, Resting energy expenditure, Respiratory quotient


近年随着肥胖、糖尿病及高脂血症等的高发,非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)的患病率有明显增高的趋势,日趋超越病毒性肝炎和酒精性肝病(alcoholic liver disease, ALD),已成为全球普遍关注的医学问题和社会问题。在我国,普通成人NAFLD患病率已高达20%~30%,其中20%~30%为非酒精性脂肪性肝炎(nonalcoholic steatohepatitis, NASH)[1,2,3]。NAFLD不但与肝细胞癌(hepatocellular carcinoma, HCC)、肝衰竭和移植肝NASH复发密切相关,而且显著增加代谢和心血管相关并发症的发病率[3,4,5]。目前,NAFLD已越来越被认识到是导致肝脏相关性致残和死亡的重要原因[6,7]

NAFLD与肥胖、糖尿病、高脂血症等代谢综合征密切相关[8]。有研究者认为NAFLD为代谢综合征在肝脏的表现[9,10]。NAFLD患者以营养过剩和代谢紊乱为特点,因此评估和监测NAFLD患者的营养和代谢状态,有着重要的临床意义[11]

但是NAFLD患者的能量代谢特点和具体的营养状况,目前临床上相关数据还不足。本研究拟通过人体成分分析仪和代谢车来评估NAFLD的营养状况和能量代谢特点,以期为临床干预提供依据。

资料与方法

一、研究对象

选取2015年6月至2017年3月于天津市第三中心医院就诊的B型超声(B超)检查结果符合脂肪肝的NAFLD患者359例为研究对象,其中男性190例,女性169例,年龄38~70岁,平均54.2岁。

入组标准:NAFLD入选对象均符合2010年中华医学会肝脏病学分会脂肪肝和酒精性肝病学组修订的《非酒精性脂肪性肝病诊疗指南》[12]。根据指南,脂肪肝诊断标准符合B超检查结果:(1)肝区近场回声弥漫性增强(强于肾脏和脾脏),远场回声逐渐衰减;(2)肝内管道结构显示不清;(3)肝脏轻至中度肿大,边缘角圆钝;(4)彩色多普勒血流显象提示肝内彩色血流信号减少或不易显示,但肝内血管走向正常;(5)肝右叶包膜及横膈回声显示不清或不完整。具备上述第1项及第2~4项中一项者为轻度脂肪肝;具备上述第1项及第2~4项中两项者为中度脂肪肝:具备上述第1项以及2~4项中两项和第5项者为重度脂肪肝。

排除标准:(1)长期饮酒史,酒精量男>30g/d,女>20g/d,连续5年以上;(2)合并病毒性肝炎;(3)合并肝硬化及肝脏恶性肿瘤;(4)妊娠和哺乳期妇女;(5)合并自身免疫性和遗传性肝病、甲状腺疾病;(6)合并感染、贫血、严重心、肺、肾等重要脏器疾病。(7)近1个月内服用任何影响糖、脂代谢的药物者。

二、方法

1.生物化学指标测定:上述人员均在禁食12h后,于晨起空腹状态下,采集外周静脉血,用于临床指标的检测:血糖、血脂总胆固醇、甘油三酯,肝肾功能,肝炎标志物,肿瘤标志物,甲状腺功能。

2.人体测量学指标的测量:上述人员均在禁食12h后,于晨起空腹状态下,排空大、小便后,着单衣,赤足,由2名经过培训的医师共同测量患者的身高、体质量、腰围(取通过腋中线肋弓最低点和髂前上嵴最高点的中点沿腰围一周的距离)、臀围(沿臀部最膨隆处测量的距离)。并计算出腰/臀比及体质量指数(body mass index, BMI),BMI=体质量(kg)/身高(m)2

3.人体成分分析测定:采用韩国产Bios Pace Inbody 720型人体成分分析仪(多频生物电阻抗法)测定细胞内水(intracellular water, ICW)、细胞外水(extracellular water, ECW)、蛋白质、脂肪、骨骼肌含量、内脏脂肪面积(visceral fat area, VFA)情况;

检测方法:测试对象于晨起空腹状态进行测量,并排空大小便,除去电子物品及金属物品;用酒精棉球擦拭电极;嘱测试对象赤足平卧于检测床上,双臂向外张开15度,不与身体接触,连接电极,待机器显示体质量后输入被测者基本资料(年龄、性别、身高),保持1~2min接受测量。

人体成分分析仪由全身四电极接触的方法,使用多频阻抗分析仪在1kHz施加交流电100mA,此后在800mA交流电下运行频率分别为5、50、100kHz。

4.代谢车的测定:采用美国Sensor Medics公司生产的Vmax229全自动肺功能诊断及代谢检测系统(简称代谢车)进行测定。

检测方法:测试前要求患者禁食8h以上,安静休息30min后平卧位,环境温度24~26℃,湿度为45%~60%。测定时室内保持安静,连续监测20min。整个试验过程要求受试者保持清醒状态并要求尽量安静不动。

测定前,代谢车主机需开机预热30min,然后进行气体流量定标和气体定标,通过后方可测试。将面罩罩在测试者头上并做好密闭,经气体分析装置分析吸进及呼出的气体中O2和CO2浓度,计算出该时间段内的耗氧量(VO2)和二氧化碳的产生量(VCO2),同时精确计算出吸入气和呼出气的体积、O2和CO2的浓度,从而计算出呼吸商(respiratory quotient, RQ),即平均CO2产生量与O2消耗量的比值。输入24h尿总氮数值,根据Weir公式:静息能量消耗(rest energy expenditure, REE)(kcal/d)=[3.941(VO2)+1.11(VCO2)]×1.44-2.17(UN)计算出实测REE及三大营养物质氧化率:碳水化合物氧化率(carbohydrate oxidation rate, CHO%)、脂肪氧化率(fat oxidation rate, FAT%)及蛋白质氧化率(protein oxidation rate, PRO%)。

5.统计学方法:采用SPSS16.0(SPSS公司,美国)统计软件进行统计学分析。首先对各组指标的正态性和方差齐性进行检验,符合正态分布的计量资料用均数±标准差(Inline graphic±s)表示,不符合正态分布的应用中位数表示;各组间比较采用单因素方差分析,若方差齐,应用LSD法进行多重比较;若方差不齐,应用Dunnett's T3法进行多重比较。对不符合方差分析的指标进行K-W非参数检验。率的比较用x2检验,以P<0.05为差异有统计学意义。

结果

1.NAFLD患者及对照组的血清学及人体测量学指标:根据腹部B型超声检测结果,将NAFLD患者分为轻度脂肪肝组和中重度脂肪肝组,其身高、体质量、腰围、臀围、腰/臀比、BMI、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、甘油三酯、总胆固醇、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-c)、低密度脂蛋白胆固醇(low-density lipogrotein cholesterol, LDL-c)、空腹血糖等生物化学指标,结果见表1

表1. 非酒精性脂肪性肝病患者和对照的测量学和生物化学指标检测结果比较.

组别 例数 性别(男/女) 年龄(岁) 身高(cm) BMI(kg/m  2 腰围 腰臀比 ALT(U/L) 甘油三酯(mmol/L) 总胆固醇(mmol/L) HDL-c(mmol/L) LDL-c(mmol/L) 空腹血糖(mmol/L)
轻度脂肪肝组 221 115/106 54.32±8.12 166.17±8.23 26.19±3.98 93.45±9.95 0.93±0.07 26(19~41) 2.09(1.85~2.32) 4.76±1.22 1.02±0.31 2.64±0.97 8.07±2.64
中重度脂肪肝组 138 75/63 54.72±6.89 167.13±9.13 28.35±5.01a 97.85±11.30a 0.95±0.07a 37(29~56)a 2.88(2.12~3.46)a 5.83±1.15 1.03±0.23 2.63±0.91 8.76±2.81
对照组 50 29/21 52.36±4.29 165.46±8.09 24.13±3.95ab 85.12±9.45ab 0.85±0.01ab 16(11~26)ab 1.41(1.10~2.43)ab 4.51±0.15b 1.31±0.05ab 2.01±0.17ab 5.20±1.45ab
统计量值 0.637 1.875 0.595 34.43 25.01 30.94 12.573 9.986 5.952 12.987 5.991 71.74
P 0.727 0.117 0.161 <0.001 <0.001 <0.001 <0.001 <0.001 0.027 <0.001 0.013 <0.001

注:ALT:丙氨酸氨基转移酶;HDL-c:高密度脂蛋白胆固醇;LDL-c:低密度脂蛋白胆固醇;符合正态分布的计量资料用均数±标准差(x¯±s)表示,不符合正态分布者应用中位数表示;对于符合方差分析的指标进行方差分析,对不符合方差分析的指标进行K-W非参数检验;a与轻度脂肪肝组比较, P<0.01;b与中重度脂肪肝组比较, P<0.01

轻度脂肪肝组、中重度脂肪肝组及对照组,其性别、年龄、身高差异均无统计学意义(P>0.05);中重度脂肪肝组较轻度脂肪肝组及对照组的BMI、腰围、腰臀比均显著升高(均P<0.001)。中重度脂肪肝组与轻度脂肪肝组及对照相比,其血清ALT、甘油三酯、总胆固醇、HDL-c、LDL-c、空腹血糖的水平显著升高(均P<0.05)。

2. NAFLD患者与对照组的人体成分分析结果:应用人体成分分析仪测量不同组别的ICW、ECW、骨骼肌、蛋白质、体脂肪、VFA,评估患者的体成分变化,结果见表2。骨骼肌含量在三组间差异无统计学意义,P=0.067;中重度脂肪肝组患者的ICW、ECW、蛋白质、体脂肪较轻度脂肪肝组及对照组均明显增加(均P<0.01),但在轻度脂肪肝组和对照组之间差异均无统计学意义;三组间VFA差异则均有统计学意义。

表2. 非酒精性脂肪性肝病患者和对照的体成分及代谢指标比较(%).

组别 例数 ICW ECW 蛋白 脂肪 骨骼肌 VFA RQ REE
轻度脂肪肝组 221 20.99±3.96 13.44±2.35 9.05±2.80 23.04±7.80 25.32±5.40 101.21±20.31 0.78±0.06 1766.21±317.12
中重度脂肪肝组 138 23.80±4.89a 15.48±2.83a 10.90±2.11a 29.13±9.23a 26.64±6.29 114.84±21.18a 0.72±0.08a 1807.87±374.40
对照组 50 19.66±2.14b 12.21±1.25b 8.67±1.84b 20.75±7.64b 25.69±5.37 85.00±16.37ab 0.80±0.02ab 1407.31±314.29ab
检验值 16.922 17.884 16.492 23.93 1.076 23.72 5.640 37.89
P <0.001 <0.001 <0.001 <0.001 0.067 <0.001 0.004 <0.001

注:ICW:细胞内水;ECW:细胞外水;VFA:内脏脂肪面积;RQ:呼吸商;REE:静息能量消耗;a与轻度脂肪肝组比较, P<0.01;b与中重度脂肪肝组比较, P<0.01

3.NAFLD患者与对照组的代谢状态比较:应用代谢车检测三组受试者的RQ、REE。将24h尿总氮数值输入机器,自动得出三大营养物质氧化率CHO%、FAT%及PRO%,结果见表3图1。本组研究显示轻度脂肪肝组及中重度脂肪肝组RQ(分别为0.78±0.06及0.77±0.08)均低于健康对照组(0.81±0.02),P=0.004。REE在轻度脂肪肝组及中重度脂肪肝组间差异无统计学意义(P=0.207),但均明显高于对照组(均P<0.001)。中重度脂肪肝组CHO%、FAT%、PRO%分别为19.49%±9.71%、66.23%±12.54%、14.22%±6.11%,与对照组相比较,存在营养物质代谢障碍,表现为碳水化合物氧化率下降,脂肪的氧化率上升。

表3. 非酒精性脂肪性肝病患者和对照组的三大物质氧化率比较.

指标 轻度脂肪肝组( n =221) 中重度脂肪肝组( n =138) 对照组( n =50) F P
CHO% 27.77±7.81 19.49±9.71a 26.46±9.26b 6.805 0.001
FAT% 58.09±12.09 66.23±12.54a 58.48±18.47b 7.165 0.001
PRO% 14.00±4.07 14.22±6.11a 14.82±5.55b 0.387 0.680

注:CHO %:碳水化合物氧化率;FAT %:脂肪氧化率;PRO %:蛋白质氧化率;a与轻度脂肪肝组比较, P<0.01;b与中重度脂肪肝组比较, P<0.01

图1. 非酒精性脂肪性肝病患者与对照组三大营养物氧化率比较.

图1

讨论

本研究结果显示,BMI、腰围、腰臀比、ALT、甘油三酯、总胆固醇、HDL-c、LDL-c及空腹血糖在轻度脂肪肝组、中重度脂肪肝组及对照组之间差异均有统计学意义。提示脂肪肝与腹型肥胖、糖脂代谢紊乱关系密切,是代谢综合征的典型表现,这与国内外报道相一致。有研究结果提示,肥胖者NAFLD患病率明显增加,在体质量指数正常的个体,腹型肥胖是NAFLD的重要危险因素[13]

人体成分分析即测量人体肌肉、蛋白和脂肪、细胞内外水等不同成分的含量。在临床上,最常用的是人体成分分析仪来进行测定和分析,即利用生物电阻抗法(BIA法)。与应用CT或MRI评估营养状态如骨骼肌和脂肪的方法相比,BIA技术更简便、便宜和安全,可作为一个可靠的评价营养状态的无创工具[14]。本研究结果可清晰显示患者身体成分的变化,主要表现为细胞内、外水的增加及蛋白、脂肪组织的增加,这可能与患者肥胖致全身细胞总数增加有关。其中VFA在三组间差异均有统计学意义,轻度脂肪肝组患者的VFA较正常组有明显升高,提示VFA可能是一个更为敏感的评估指标。

REE是决定能量消耗、预防及治疗肥胖的重要的监控指标[15]。“经典的”理论认为,肥胖人群的代谢相对缓慢[16],但近年来,出现了越来越多的相反的声音,认为肥胖人群的REE更高[17,18,19,20]。我们的研究显示,中重度脂肪肝组其REE较对照组有明显升高,这与先前的研究相一致。这可能与其体质量明显增加有关[21]

REE受多种因素的影响。有研究显示,REE与脂肪含量明显相关[22]。还有研究认为,REE的主要决定因素是人体组成,特别是代谢活性高的组织,如去脂体质量(fat-free mass, FFM)。FFM包括骨、骨骼肌含量和高代谢活性器官,如脑、心脏、肝脏、肾脏及胃肠道[23]。因此不同的身体组成直接影响REE。大多数研究中观察到的肥胖人群,其REE较高是由于人体组成的失衡[24,25]

在氧化过程中,脂肪、蛋白质、碳水化合物的呼吸商分别约为0.7、0.8和0.95~1。易肥胖的人群,其肌肉的交感神经活性低,可能影响呼吸商[26]。有研究显示,RQ与体质量呈负相关,体质量越低,呼吸商越高[27]。这与本研究的结果相一致。还有研究认为,RQ的升高,可以作为病情恢复的评价指标[28]

从三大营养物质的氧化率上看,中重度脂肪肝患者CHO%下降,FAT%升高,PRO%变化无明显差异。碳水化合物的氧化率明显降低,提示葡萄糖利用障碍,这可能与胰岛素抵抗有关[29],肝脏疾病越重,其碳水化合物的氧化率越低而脂肪和蛋白质的氧化率越高[28]。这从营养学角度再次证实了脂肪肝和胰岛素抵抗的密切关系。

综上所述,本研究显示NAFLD患者营养失衡和能量代谢紊乱状态明显。内脏脂肪含量明显增加,REE升高、呼吸商减低,三大营养物的氧化率失衡,主要表现在碳水化合物氧化率的下降和脂肪氧化率的升高。应用人体成分分析仪及代谢车可以综合评估NAFLD患者的营养及能量代谢状态,可以为临床干预及监测病情提供依据。但本研究尚存在一定不足,首先,本研究为单中心研究,还需大数据的进一步补充以减少偏倚;其次,本研究为横断面的观察性研究,尚缺乏干预及进一步的机制研究,这将在今后的研究中进一步深入探讨。

利益冲突

作者贡献声明

叶青:酝酿和设计实验,起草文章,统计分析;刘芳:采集数据,分析/解释数据,对文章的知识性内容作批评性审阅,支持性贡献;王昕:采集数据,统计分析;齐玉梅:分析/解释数据,对文章的知识内内容作批评性审阅,行政、技术或材料支持;韩涛:酝酿和设计实验,对文章的知识性内容作批评性审阅,指导;王凤梅:酝酿和设计实验,对文章的知识性内容作批评性审阅,行政、技术或材料支持,指导

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