非酒精性脂肪肝胰岛素抵抗及血清瘦素和脂联素水平的研究

[目的]研究非酒精性脂肪肝(NAFLD)患者胰岛素抵抗指数(IRI)、瘦素和脂联素水平的变化,探讨疾病发病中胰岛素抵抗(IR)、瘦素和脂联素的作用.[方法]测定体检和住院人群中NAFLD并肥胖(NAFLD)组、单纯性肥胖(肥胖)组和正常对照组空腹血糖、空腹血清胰岛素,采用稳态模型法计算IRI,同时检测瘦素和脂联素水平.[结果]NAFLD组空腹胰岛素水平和IRI显著高于肥胖组和对照组(P＜0.05);NAFLD组和肥胖组的瘦素水平显著高于对照组(P＜0.05);NAFLD组和肥胖组的脂联素水平显著低于对照组(P＜0.05);直线相关分析后,IRI与血清瘦素水平呈显著正相关(r=0.169 3,P＜0.01);而与血清脂联素水平呈显著负相关(r=-0.218 7,P＜0.01).[结论]IR可能是NAFLD发生、发展的基础,IR构成NAFLD患者基本特征之一,中央型肥胖是NAFLD的危险因素;NAFLD患者瘦素水平升高而脂联素水平降低,瘦素和脂联素通过不同机制参与了IR的发生、发展,进而影响NAFLD的发病.     

非酒精性脂肪性肝病患者血清瘦素、脂联素的变化

目的:探讨非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患者血清瘦素、脂联素的变化.方法:选取NAFLD患者60例,与健康组60例相对照.ELISA法测定血清瘦素、脂联素水平,并与体质量指数(BMI)、腰臀比(WHR)、甘油三脂(TG)、总胆固醇(Tchol)、高密度脂蛋白胆固醇(HDL-C)、血糖(FBG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)相结合,从而判定瘦素、脂联素在NAFLD中的作用.结果:NAFLD组与正常对照组相比,血清瘦素水平升高(12.37±1.99μg/L vs 5.20±41.03 μg/L,P<0.01),脂联素水平降低(12.69±2.83 mg/Lvs 22.83±4.61 mg/L,P<0.01).Logistic多因素回归分析显示瘦素与WHR、HOMA-IR、FBG呈独立正相关(β=8.175,0.974,0.564,P<0.01).脂联素与HOMA-IR、BMI呈独立负相关(β=-0.495,-0.3 14,P<0.01).结论:NAFLD患者血清瘦素水平升高,脂联素水平降低,这两种细胞因子均与胰岛素抵抗相关.     

血脂联素和瘦素水平对老年男性高血压的预测作用

目的:研究脂联素、瘦素水平对老年男性高血压的预测作用。方法:93例老年非高血压男性患者入选,采用放射免疫法测定其血脂联素、瘦素水平。随访中位时间为56(四分位间距:47.5,61.0)个月。结果:①基线水平脂联素/瘦素比值的中位数为1.449,入选患者按脂联素/瘦素比值分为≤1.449组(低比值组)与1.449组(高比值组),低比值组体质量指数(body mass index, BMI)、糖化血红蛋白(glycated hemoglobin, HbA_(1c))、三酰甘油(triglyceride,TG)及随访56个月后的高血压发病率明显高于高比值组,高密度脂蛋白胆固醇水平则明显低于高比值组(P0.05)。②随访56个月后,93例患者中48例进展为高血压。高血压组年龄、BMI、收缩压、空腹胰岛素水平及稳态模型的胰岛素抵抗指数(homeostasis model assessment-insulin resistance,HOMA-IR)均明显高于非高血压组,而稳态模型的胰岛素敏感指数(HOMA-insulin sensitivity,HOMA-IS)及脂联素/瘦素比值则明显低于非高血压组(P0.05)。③Logistic单因素回归分析提示基线年龄、收缩压水平、BMI及血瘦素水平是老年男性高血压发生的风险因素,而HOMA-IS是老年男性发生高血压的保护性因素(P0.05)。Logistic多因素回归分析提示基线收缩压水平是老年男性高血压发生的风险因素(P0.05)。④脂联素/瘦素比值与HOMA-IR负相关(r=-0.236, P=0.034),与HOMA-IS正相关(r=0.350, P=0.001)。结论:血脂联素、瘦素水平对老年男性高血压的发生有一定的预测作用。     

非酒精性脂肪性肝病患者血清瘦素和脂联素与胰岛素抵抗的关系

目的 探讨非酒精性脂肪性肝病(NAFLD)患者血清瘦素、脂联素的变化及其与胰岛素抵抗的关系. 方法 选取NAFLD患者60例,同期门诊体检健康者60名为对照组,ELJSA法测定血清瘦素、脂联素水平,并检测体质量指数、腰臀比、甘油三酯、总胆固醇、高密度脂蛋白胆固醇(HDL-C)、空腹血糖、ALT、AST、γ-谷氨酰转肽酶(GGT),稳态模型评估的胰岛素抵抗指数(HOMA-IR).采用SPSS10.0软件包进行统计学分析,计量资料差异性比较用方差分析和t检验,多因素相关性用Spearman分析和Logistic回归分析. 结果 血清瘦素、脂联素水平NAFLD组分别为(12.37±1.99)μg/L和(12.69±2.83)mg/L,对照组分别为(5.20±1.03)μg/L和(22.83±4.61)mg/L,t值分别为24.661和14.516,P值均<0.01;HOMA-IR,NAFLD组为4.86±0.63,对照组为1.91±0.41,t值为30.451,P<0.01.Logistic多因素回归分析显示瘦素与腰臀围之比、HOMA-IR、空腹血糖呈独立正相关,β值分别为8.175、0.974和0.564,P值均<0.01;脂联素与HOMA-IR、体质量指数呈独立负相关,β值分别为-0.495和-0.314,P值均<0.01.结论 NAFLD患者血清瘦素、脂联素的变化与胰岛素抵抗有关.     

非酒精性脂肪性肝病患者血清脂联素和瘦素水平变化

目的研究血清脂联素和瘦素水平与非酒精性脂肪性肝病(NAFLD)的关系。方法应用放射免疫分析法检测56例NAFLD患者和42例健康人血清脂联素、瘦素、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白ApoA、ApoB、胰岛素、胰岛素抵抗指数、体质量指数。结果对照组和NAFLD患者血清脂联素分别为12.4±3.2mg/L和6.1±1.9mg/L(P<0.01),高密度脂蛋白胆固醇为1.2±0.3mmol/L和1.0±0.3mmol/L(P<0.05),瘦素为5.3±1.4μg/L和9.2±2.1μg/L(P<0.01),胰岛素为9.4±4.2IU/L和18.5±7.8IU/L(P<0.01),甘油三酯为1.0±0.5mmol/L和2.4±1.2mmol/L(P<0.01),低密度脂蛋白胆固醇为2.2±0.6mmol/L和2.8±0.7mmol/L(P<0.05),体质量指数为21.5±2.1kg/m2和28.3±3.2kg/m(2P<0.01),胰岛素抵抗为1.1±0.4IU/mmol和3.8±2.21u/mmo(lP<0.01);脂联素水平与瘦素、体质量指数和胰岛素抵抗呈负相关(r=-0.552,-0.497,-0.513,P均<0.01)。结论 NAFLD患者血清脂联素水平下降,瘦素水平升高,且与胰岛素抵抗相关。     

血清脂联素与老年人非酒精性脂肪肝的相关性研究

目的探讨血清脂联素水平、胰岛素抵抗与老年人NAFLD及其合并代谢紊乱的相关性。方法随机选取NAFLD合并代谢紊乱患者89例，NAFLD患者95例，正常对照80例，测定BMI及临床生化指标并进行肝脏B超检查。放射免疫法测定空腹胰岛素水平，计算HOMA指数，同时ELISA法测定血清脂联素水平。将老年组与青年组、老年肥胖组与非肥胖组进行比较。结果老年人NAFLD存在胰岛素抵抗及血脂、血糖及肝功能代谢异常，脂联素水平降低，合并代谢紊乱者脂联素水平更低。老年人NAFLD合并代谢紊乱者血清脂联素水平高于年轻患者。老年肥胖及年轻NAFLD容易发生肝功能异常。多元回归分析表明，脂联素与BMI、性别及HOMA相关。结论老年人NAFLD及其合并代谢紊乱患者胰岛素抵抗严重，脂联素水平降低；老年肥胖NAFLD患者更容易发生ALT异常。血清脂联素水平与BMI、性别及HOMA相关，与年龄无显著相关性。     

不同血糖水平老年人脂联素、瘦素水平及其比值与胰岛素抵抗的相关性

目的研究不同血糖水平老年人脂联素、瘦素水平的变化,脂联素瘦素比值与胰岛素抵抗的相关性。方法选取不同血糖水平老年人146例,包括对照组:糖耐量正常的健康人群52例,研究组:糖耐量异常(IGT)患者39例,新近诊断糖尿病(T2DM)患者55例。研究脂联素、瘦素水平以及其比值和胰岛素抵抗指数、体重指数、腰臀比、血脂等指标的相关性。结果 IGT组和T2DM组的腰臀比、体重指数、甘油三酯、瘦素、胰岛素抵抗指数较正常对照组显著增加,脂联素水平较正常组明显下降;脂联素/瘦素与腰围、腰臀比、体重指数、空腹胰岛素、甘油三酯、低密度脂蛋白、HO-MA-IR负相关,与高密度脂蛋白正相关。Logistic回归结果显示脂联素/瘦素是胰岛素抵抗指数的独立危险因素。结论不同血糖水平老年人中,脂联素/瘦素比值与胰岛素抵抗密切相关。     

2型糖尿病合并非酒精性脂肪肝患者的胰岛素、血脂及脂联素的变化

对2型糖尿病合并非酒精性脂肪肝患者的脂联素、空腹血糖、胰岛素及甘油三酯、胆固醇进行监测,并与不合并非酒精性脂肪肝2型糖尿病组及正常对照组进行比较.结果糖尿病组脂联素、胰岛素敏感指数较正常对照组降低(P均<0.05);合并脂肪肝组与不合并脂肪肝组比较,脂联素水平、胰岛素敏感指数明显降低,甘油三酯、胆固醇水平明显增高;差异均有统计学意义(P均<0.05).认为2型糖尿病合并非酒精性脂肪肝与脂联素、胰岛素抵抗、脂代谢紊乱有关.     

脂联素与维吾尔族非酒精性脂肪肝病的关系

目的:探讨脂联素与维吾尔族非酒精性脂肪肝病(non-alcoholic fatcy liver disease,NAFLD)的关系.方法:选择非酒精性脂肪肝患者260人(脂肪肝组)和健康对照129人(正常对照组),均为维吾尔族,检测血压、身高、体质量,抽取空腹及OGTT的2h静脉血,检测血脂、胰岛素、血糖及脂联素水平,计算BMI、HOMA-IR,分析脂联素与NAFLD及上述指标的关系.结果:在校正性别、年龄、BMI、SBP、DBP、TC、HDL、LDL、TG、FBG、PBG、FINS、PINS的影响因素后,与正常组相比,脂肪肝组血清脂联素水平降低,差异具有统计学意义;而脂肪肝组患病率、BMI、SBP、DBP,TC,HDL,LDL,TG,FBG,PBG,FINS、HOMA-IR水平随着血清脂联素的增高呈现下降趋势(P＜0.05);Logistic回归分析结果提示在校正了性别、年龄、BMI、SBP、DBP、HOMA-IR、TC、HDL、LDL、TG、FBG、PBG、FINS、PINS的影响的情况下,以血清脂联素四分位最低层为对照,第二、三、四分位层时患脂肪肝的OR值分别为0.460(P=0.03 1)、0.449(P=0.022)、0.099(P=0.000).结论:维吾尔族NAFLD脂联素水平降低,亦是其独立危险因素.     

瘦素与妊娠糖尿病患者胰岛素抵抗及胎儿发育的相关性

目的 探讨瘦素及可溶性瘦素受体(sLR)在妊娠糖尿病发病及胎儿发育中的作用.方法 选取2014年1月至12月在厦门大学附属成功医院连续产检并分娩的673名孕妇为研究对象,跟踪随访至孕晚期.根据糖耐量试验结果,采用随机抽样法选取50例血糖控制良好的妊娠糖尿病患者纳入妊娠糖尿病组,根据一般资料进行匹配选取50名糖耐量试验结果阴性者纳入正常妊娠组.根据妊娠周数分为孕早期和孕晚期亚组,比较两组不同孕期血清及脐血瘦素、sLR、脂联素、抵抗素及生化指标水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR),精确测量新生儿生长发育指标,使用多元Logistic回归分析孕早期胰岛素抵抗的危险因素,同时采用Spearman相关性分析血清瘦素与sLR、脂联素、抵抗素及生化指标水平的相关性.结果 与正常妊娠组相比,妊娠糖尿病组孕早期血清瘦素、甘油三酯、总胆固醇、低密度脂蛋白-胆固醇(LDL-C)、空腹胰岛素(FINS)、HOMA-IR明显升高(t=0.938～6.864,P均＜0.05),sLR、脂联素显著降低(t=9.237、2.216,P均＜0.05),抵抗素、高密度脂蛋白-胆固醇(HDL-C)、空腹血糖差异无统计学意义(P均＞0.05).与正常妊娠组相比,妊娠糖尿病组孕晚期血清瘦素、抵抗素、空腹血糖、FINS、甘油三酯、总胆固醇、LDL-C、HOMA-IR明显升高(t=0.429 ～ 13.787,P均＜0.05),sLR、脂联素显著降低(t=2.216、5.623,P均＜0.05),HDL-C差异无统计学意义(P＞0.05).与正常妊娠组相比,妊娠糖尿病组脐血瘦素、抵抗素明显升高(t=1.007、11.857,P均＜0.05),sLR、脂联素显著降低(t=0.201、4.558,P均＜0.05).多元Logistic回归分析显示,瘦素(OR =1.288,95％ CI:1.137 ～4.370)、抵抗素(OR=1.223,95％CI:1.035～ 1.570)、总胆固醇(OR=1.216,95％CI:1.026 ～1.823)、甘油三酯(OR=1.357,95％CI:1.008～ 3.572)、LDL-C (OR=1.634,95％ CI:1.251～3.764)是妊娠糖尿病组孕早期发生胰岛素抵抗的独立危险因素,sLR (OR =0.714,95％ CI:0.161～0.893)、脂联素(OR =0.352,95％CI:0.112 ～0.510)是妊娠糖尿病组孕早期发生胰岛素抵抗的保护性因素.妊娠糖尿病组孕晚期母体血瘦素含量与sLR、脂联素均呈负相关(r=-0.16、-1.13,P均=0.000),与抵抗素呈正相关(r=0.269,P=0.019).妊娠糖尿病组脐血瘦素含量与sLR、脂联素均呈负相关(r=-0.147、-1.250,P均=0.000),与抵抗素、体重、Ponderal 指数均呈正相关(r =0.410、0.673、0.301,P均＜0.05),与头围、身长无关(P均＞0.05).结论 瘦素及sLR与妊娠糖尿病患者胰岛素抵抗存在相关性,但与胎儿宫内生长和发育无关.     

Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease

OBJECTIVES: To explore associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND PATIENTS: In a cross-sectional study, we enrolled 60 consecutive NAFLD patients and 60 age-, sex- and body mass index (BMI)-matched healthy controls. MEASUREMENTS: NAFLD (by liver biopsy), plasma adiponectin concentrations, insulin resistance (by homeostasis model assessment, HOMA-IR) and metabolic syndrome (MetS) features. RESULTS: NAFLD patients had a marked decrease in plasma adiponectin concentration (6.1 +/- 2.8 vs. 13.6 +/- 3.8 microg/ml, P < 0.001) compared with matched controls. MetS, as defined by the Adult Treatment Panel III (ATP III) criteria, and its individual components were more frequent among NAFLD patients. The marked differences in adiponectin concentrations that were observed between the groups were little affected by adjustment for age, sex, BMI, HOMA-IR score and MetS components. Notably, decreased adiponectin levels were closely associated with the degree of hepatic steatosis, necroinflammation and fibrosis (P < 0.001 for all) among NAFLD patients. By logistic regression analysis, low adiponectin levels independently predicted hepatic steatosis [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.5-5.8, P < 0.001] and necroinflammation (OR 3.1, 95% CI 1.9-7, P < 0.001), but not fibrosis (P = 0.07), after adjustment for age, sex, BMI, HOMA-IR and MetS components. CONCLUSIONS: NAFLD patients have markedly lower plasma adiponectin concentrations than control subjects. Low adiponectin levels are strongly associated with the severity of liver histology, thus further supporting the hypothesis that adiponectin might be involved in the development of NAFLD.     

Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity

Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) histological features at liver biopsy (n = 116). When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender, and plasma high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R(2), 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R(2), 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R(2), 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.     

Leptin in nonalcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. Methods: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student’s t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. Results: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). Conclusion: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.     

女性非酒精性脂肪性肝病脂联素水平与胰岛β细胞功能及胰岛素抵抗的相关性

目的探讨女性非酒精性脂肪性肝病（NAFLD）脂联素水平与胰岛β细胞功能、胰岛素抵抗之间的关系。方法应用高葡萄糖钳夹技术检测了9例NAFLD组和7例正常对照组（C）胰岛β细胞功能和胰岛素敏感性,采用梯度回波化学位移MRI评估了肝脏inphase（IP）值和outphase（OP）值,并测定了皮下脂肪面积（SA）、内脏脂肪面积（VA）。用酶联免疫法测定脂联素（adiponectin）水平。结果 NAFLD组空腹胰岛素（FINS）、胰岛素分泌第一时相（1Ph）、葡萄糖代谢清除率（M）、胰岛素敏感指数（ISI）和脂联素水平低于C组（P〈0.05）。Spearman相关分析显示,脂联素与M（r=0.526,P=0.036）、ISI（r=0.682,P=0.005）、1Ph（r=0.676,P=0.003）、肝脏OP值（r=0.682,P=0.004）和肝脏OP/IP（r=0.594,P=0.015）呈正相关。结论女性NAFLD患者脂联素水平降低,低脂联素血症可能与胰岛素抵抗、胰岛功能早期损害密切相关。     

Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients

CONTEXT: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. OBJECTIVE: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. DESIGN, SETTING, AND PARTICIPANTS: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). MAIN OUTCOME MEASURES: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. RESULTS: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels. CONCLUSIONS: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.     

Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease

BACKGROUND/AIMS: Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD) remains undefined. We aimed at determining the relation between leptin and liver fibrosis in human NAFLD. METHODS: Human plasma leptin and several indicators of insulin resistance were measured in 88 NAFLD patients and matched controls. RESULTS: Leptin levels were significantly greater in patients with more advanced fibrosis (P = 0.005). By multivariate analysis, the significant association between leptin and fibrosis was abolished (adjusted P = 0.3) when controlling for confounders including age, gender, BMI, diabetes and insulin resistance. Only age (adjusted P = 0.006) and insulin sensitivity (adjusted P = 0.04) correlated significantly with fibrosis stage. A second liver biopsy was performed in 39 out of the 88 patients at 27.9 +/- 16 months. Leptin levels were not significantly different between patients who had fibrosis progression (n = 10) and those who did not (n = 29). CONCLUSIONS: In human NAFLD, no relationship between leptin levels and fibrosis stage was demonstrated. The correlation of leptin and fibrosis severity seems to be an indicator of the factors that determine leptin production.     

Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.