血清脂联素、瘦素水平与2型糖尿病家系胰岛素抵抗的关系

目的探讨2型糖尿病（T2DM）家系正常糖耐量一级亲属（简称一级亲属）血清脂联素、瘦素水平的变化，研究脂联素、瘦素与胰岛素抵抗（IR）的关系。方法收集T2DM家系45个。在排除DM和糖耐量减退的前提下，选择一级亲属为观察组（83例），先证者或其同胞的配偶为正常对照组（76例），检测所有受试者脂联素、瘦素水平，计算胰岛素抵抗指数（HOMA—IR）。结果观察组的脂联素水平显著低于对照组（P〈0．01），HOMA—IR、瘦素显著高于对照组（P〈0．05）。相关分析显示，脂联素与瘦素呈负相关。多元线性逐步回归分析显示，脂联素、瘦素是影响T2DM家系一级亲属IR的独立危险因素。结论T2DM家系一级亲属在未发生DM时已存在IR抵抗，脂联素与瘦素都参与了IR发生过程。     

血清脂联素与新诊断2型糖尿病病人及代谢综合征患者的关系

目的对血清脂联素水平与新诊断2型糖尿病及代谢综合征患者的关系进行观察和分析。方法测定140例新诊断2型糖尿病患者与80例非糖尿病患者空腹血清脂联素及血糖、血脂、血压等指标，并分析各指标与脂联素的相关性。结果（1）新诊断2型糖尿病患者的血清脂联素水平显著降低。（2）随着代谢综合征指标的增多，脂联素含量呈下降趋势。（3）新诊断为糖尿病组中脂联素与代谢综合征、男性、体重指数呈负相关，与高密度脂蛋白胆固醇呈正相关。结论血清脂联素浓度与2型糖尿病及代谢综合征密切相关，低脂联素血症是糖尿病及代谢综合征的又一特征，在其发病中可能起重要的作用。     

Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels

Abstract: Background: Adiponectin is a hormone secreted by adipocytes and has anti‐diabetic and anti‐atherogenic properties. Hypoadiponectinemia is associated with insulin‐resistant diabetes and liver dysfunction. The aim of this study was to determine plasma adiponectin and insulin levels in patients with liver cirrhosis. Methods: Adiponectin and insulin levels were determined in 38 patients with cirrhosis and 30 healthy controls, and were correlated with various clinical and biochemical parameters. Patients included 21 with Child A, eight Child B, and nine with Child C liver cirrhosis. Results: Log adiponectin and insulin levels were significantly elevated in patients with cirrhosis compared with the control. In liver cirrhosis, the level of adiponectin increased proportionately with the Child's classification score. In control subjects, plasma adiponectin correlated inversely with insulin levels. In contrast, plasma adiponectin correlated positively with insulin levels in patients with liver cirrhosis. Plasma adiponectin levels did not correlate with age, sex, body mass index, total bilirubin, aspartate aminotransferase, and fasting blood sugar levels in both groups, while alanine aminotransferase correlated negatively with adiponectin in control subjects as reported previously. Conclusion: Our results of high plasma adiponectin in patients with liver cirrhosis could reflect an imbalance between its production by adipocytes and metabolism in the liver.     

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.     

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist increases plasma adiponectin levels in type 2 diabetic patients with proteinuria

Adiponectin appears to be an important modulator for metabolic and vascular diseases. A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2 diabetic patients with proteinuria. Sixty-four patients (mean age, 46.1±4.6 yr; 30 male, 34 female) and 26 healthy volunteers (mean age, 45.3±4.8 yr; 14 male, 12 female) were included. Patients with proteinuria were treated with 4-mg/d rosiglitazone (n = 21, 10 males, 11 females) for 4 wk. Adiponectin levels in patients were significantly lower than those of controls (p<0.001). There were significant negative correlations between adiponectin concentrations and insulin levels as well as homeostasis model assessment (HOMA) index in patient’s group (r=−0.538, p<0.001; r,=−0.393, p=0.001, respectively). There was also a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r=−0.526, p=0.002). Plasma adiponectin levels in patients with proteinuria ?(n=31; 3.91±2.57 μg/mL) were significantly lower than those without proteinuria (n=33; 10.15±1.97 μg/mL) (p<0.001). After the treatment period, adiponectin levels significantly increased (p<0.001) and proteinuria, plasma insulin, and HOMA indexes significantly decreased in treatment group (p<0.001, p<0.001, p<0.001, respectively). The results suggest that adiponectin is inversely correlated with proteinuria and treatment with peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist rosiglitazone both corrects proteinuria and increases the low adiponectin levels in diabetic patients.     

糖尿病大血管并发症与血清高分子质量脂联素水平的相关性

目的探讨2型糖尿病大血管并发症与血清高分子质量脂联素（HMM-ADPN,H-ADPN）水平之间的相关性。方法选取2010年12月至2012年12月接受治疗的106例2型糖尿病患者,分为单纯2型糖尿病组（A组,n=66）和2型糖尿病合并大血管病变组（B组,n=40）。测量所有受试者的身高、体质量、血压,同时分别测定高密度脂蛋白胆固醇（HDL．C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）、总胆固醇（TC）、糖化血红蛋白（HbAlc）、空腹血糖（FBG）、高敏C．反应蛋白（hs-CRP）、血清总脂联素（ADPN）、H．ADPN、空腹胰岛素（FINS）、颈动脉内膜中层厚度（CIMT）等。结果两组间血清H-ADPN水平差异有统计学意义（P〈0．05）,多因素logisticl回归分析显示,调整年龄、性别、体质量指数（BMI）及hs．CRP等因素后血清H．ADPN水平与HDL-C水平呈显著正相关（P〈0．05）,与收缩压及CIMT呈负相关（P〈0．05）.结论血清H．ADPN水平在糖尿病动脉粥样硬化过程中可能起重要作用,与2型糖尿病大血管并发症的发生和发展相关。     

Lower plasma adiponectin is correlated to higher alanine aminotransferase independent of metabolic factors and hepatitis B virus carrier status

Background: Adiponectin has been linked to the metabolic syndrome and coronary artery disease in recent years. The animal and human data also suggest that adiponectin may be beneficial for liver functions. The aim of this study was to investigate the correlation between plasma adiponectin level and liver function tests in adults with or without chronic hepatitis B virus (HBV) infection. Methods: We analysed the blood levels of liver enzymes and adiponectin in 140 apparently healthy adults, including 21 HBV carriers. Results: We found that the plasma adiponectin levels were inversely correlated to aspartate aminotransferase (r = −0.314, P = 0.000) and alanine aminotransferase (ALT) (r = −0.430, P = 0.000). Among the HBV carriers, the ALT correlated with the plasma adiponectin levels (r = −0.521, P = 0.015). In linear regression models adjusting for age, sex and the other metabolic variables, the ALT was independently related to the plasma adiponectin levels (β = −0.371 ± 0.134, P = 0.007), even in HBV carriers (β = −1.143 ± 0.482, P = 0.034). The ALT was also independently correlated to the plasma adiponectin levels (β = 0.552 ± 0.132, P < 0.001) with adjustment for age, sex and insulin‐resistance index by homeostasis model assessment, even in HBV carriers (β = −1.202 ± 0.562, P = 0.048). The subjects with normal ALT had a significantly higher least square mean of plasma adiponectin than those with abnormal ALT (4.01 ± 0.19 vs 3.30 ± 0.30, P = 0.014) with adjustment for age, sex, homeostasis model assessment insulin resistance and HBV status. Conclusion: ALT was inversely related to adiponectin levels, independent of the metabolic factors and HBV status. Whether there is any potential prognostic and therapeutic value of adiponectin in human liver diseases remains to be investigated.     

2型糖尿病患者非糖尿病后代心率变异性与血清脂联素水平的相关性研究

目的旨在探讨血清脂联素浓度降低是否与2型糖尿病(T2DM)患者非糖尿病后代心率变异性(heart rate variability,HRV)改变有关.方法31例(男16例,女15例)T2DM患者,所有子女(91例)排除已进行药物治疗的T2DM患者14例,其余空腹静脉取血测定血浆葡萄糖,排除≥7.0 mmol/L者3例,排除5.6~7.0 mmol/L之间者7例.选择其空腹血糖≤5.6 mmol/L后代行口服葡萄糖耐量试验,均未达到T2DM诊断标准,分为正常葡萄糖耐量组(NGT,n=32),葡萄糖耐量异常组(IGT,n=35),对照组(n=32)为无糖尿病家族史的健康查体者.行24 h动态心电图检查测定HRV,指标包括:全部正常窦性R-R间期值的标准差(SDNN);全程按5 min分成连续的时间段,先计算每5 min正常R-R间期的平均值,再计算所有平均值的标准差(SDANN);全部相邻R-R间期差的均方根(rMSSD);总功率(TP);低频功率(LF);高频功率(HF).ELISA法测定血清脂联素.结果T2DM非糖尿病后代血清脂联素水平与其体重指数(BMI)、空腹胰岛素负相关,与高密度脂蛋白胆固醇(HDL-c)、SDNN、SDANN、rMSSD、TP、LF、HF正相关.对照组、NGT组、IGT组之间血清脂联素逐渐降低、空腹胰岛素、SDNN、SDANN、rMSSD、TP、LF、HF逐渐升高.IGT组BMI、血清三酰甘油高于HDL-c,低于对照组和NGT组.结论自主神经平衡的改变与胰岛素抵抗和血清脂联素水平改变具有相关性.     

糖耐量正常的2型糖尿病一级亲属血清脂联素与胰岛素抵抗、血管内皮功能的关系

目的分析糖耐量正常的2型糖尿病患者一级亲属（FDR s）的血清脂联素与胰岛素抵抗（IR）、血管内皮功能之间的关系,探讨糖尿病早期内皮损伤的发病机制。方法选取正常对照组31例和FDR s组57例,其中FDR s组肥胖者26例,非肥胖者31例,分别测定血糖、血脂、胰岛素、血清脂联素、FFA水平,评估胰岛素敏感性,并用二维超声成像扫描法测定血管内皮功能。结果与正常对照组比较,FDR s组内皮依赖性血管舒张功能、胰岛素敏感指数、血清脂联素水平降低,且肥胖组显著低于非肥胖组,差异均有统计学意义（P均〈0.05）结论糖耐量正常的FDR s已经存在IR和血管内皮功能受损,低脂联素水平、IR与血管内皮功能失调之间关系密切。     

High molecular weight form of adiponectin levels of Japanese patients with chronic hepatitis C virus infection

Aim: The aim of the present study was to clarify the correlation between serum adiponectin level and the properties of hepatitis C virus (HCV). Methods: A meal test was carried out for insulin resistance assessment in 81 patients with chronic HCV infection. Blood samples were taken before and after the test to measure serum insulin and plasma glucose (PG). The adiponectin level was measured by enzyme-linked immunosorbent assay in each patient. Results: Serum adiponectin levels were significantly correlated with the area under the insulin curve (AUC-insulin)during the meal test and with serum HCV-RNA level. Multiple regression analysis showed age to be a significant independent parameter associated with an increased adiponectin level, whereas male sex, fasting insulin, and serum HCV-RNA level were significant independent parameters associated with a decreased adiponectin level. Conclusion: It is possible that insulin resistance in patients with chronic HCV infection is related to adiponectin secretion.     

Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population.

AIMS: To investigate any association between Type 2 diabetes mellitus and two single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T, in the Korean population. METHODS: We genotyped 427 non-diabetic controls and 493 Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured plasma adiponectin concentrations, and examined clinical parameters in Koreans. RESULTS: There were no statistically significant differences in allele frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12 for SNP276). The genotype distributions of these SNPs had no association with the risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma levels of adiponectin were not statistically different according to T45G and G276T either, in both control and Type 2 diabetic subjects. CONCLUSION: The T45G and G276T of the adiponectin gene may not be an important determinant of Type 2 diabetes or insulin resistance in Korean subjects.     

沉默信息调节因子1对早期2型糖尿病大鼠脂联素的调节作用

目的检测脂联素水平及沉默信息调节因子1(SIRT1)在早期糖尿病(DM)大鼠肝脏组织中的表达变化,探究SIRT1对脂联素的调控作用。方法 Sprague-Dawley大鼠42只,分为4组:正常对照组(n=10)、DM组(n=10)、DM+白藜芦醇(RES)组(n=11)和DM+尼克酰胺(NIA)组(n=11)。高脂饮食联合链脲佐菌素建立2型DM大鼠模型。进行基础代谢和血清学检测,HE染色法观察肝脏病理结构变化,酶联免疫吸附试验(ELISA)试剂盒检测血清脂联素水平;Western blotting和逆转录-聚合酶链反应法检测肝组织SIRT1和脂联素受体(AdipoR)等表达变化。采用SPSS 19.0软件进行数据处理。组间比较采用方差分析及t检验。结果与DM组相比,空腹血糖(FBG)在DM+RES组显著降低(P0.05);总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)在DM+RES组显著降低(P0.01),在DM+NIA组显著升高(P0.05);甘油三酯(TG)在DM+RES组显著降低(P0.05);高密度脂蛋白胆固醇(HDL-C)在DM+RES组显著升高(P0.01)。与DM组相比较,DM+RES组的脂联素水平略有升高(P0.05),DM+NIA组血清脂联素水平显著降低(P0.05)。显微镜下,DM组大鼠肝脏可见不同程度炎细胞浸润、甚至变性,DM+RES组大鼠肝脏脂肪变性减轻,DM+NIA组大鼠肝脏肝细胞散在小泡性脂滴。与DM组相比较,DM+RES组AdipoR2和SIRT1蛋白表达显著增加(均P0.05),WISP-1蛋白表达显著降低(P0.05),而DM+NIA组AdipoR2和SIRT1蛋白表达显著降低。与DM组比较,AdipoR2和SIRT1 mRNA在DM+RES组表达显著增加(P0.01),WISP-1 mRNA表达显著降低(P0.01);而DM+NIA组AdipoR2表达显著降低(P0.05)。结论在早期DM肝损伤的发生发展过程中,SIRT1信号分子可能通过调节AdipoR的表达来调控脂联素的水平,参与DM内分泌系统的病理生理演变。     

Raised alanine transaminase and decreased adiponectin are features of the metabolic syndrome in patients with type 2 diabetes

AIM: The aim of the study was to investigate the relationship between the metabolic syndrome (MS), adiponectin and abnormal liver enzymes in patients with type 2 diabetes. METHODS: Fasting serum was collected from 189 patients with type 2 diabetes, adiponectin was measure using radioimmunoassay and features of the MS were assessed. RESULTS: Mean ALT was significantly higher in patients with the MS and higher ALT was associated with lower adiponectin levels. As the number of features of MS increased, ALT increased and adiponectin decreased independent of glycaemic control. CONCLUSION: Hypoadiponectinemia and the MS may be linked with liver injury in patients with type 2 diabetes.     

吡格列酮与二甲双胍治疗2型糖尿病的疗效比较

在4个临床中心观察吡格列酮(104例)和二甲双胍(104例)治疗12周对2型糖尿病的闻疗效并进行比较,结果显示这两种药物均使空腹和餐后血糖、HbA_(1c)明显下降(均P<0.05),两组疗效相似。两组不良事件发生率相似。     

Effects of insulin administration in a group of high-risk, non-diabetic, first-degree relatives of Type 1 diabetic patients: an open pilot trial.

AIMS: To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve beta-cell rest, in a group of high-risk, non-diabetic first-degree relatives of Type 1 diabetic patients. METHODS: Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8+/-9.6 years) defined as: first-degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) > or =20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test < or =10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR. RESULTS: Three out of five subjects in both groups developed Type 1 DM during follow-up: after 21, and 32-57 months in the insulin-treated group and after 4, and 18-60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA-DR3 or DR4 alleles, whereas only one of the non-progressors had these parameters (P < 0.05). During follow-up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups. CONCLUSION: The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high-risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the development of overt disease. The efficacy and safety of insulin used at either a different dose or by a different route, as well as its potential effect in the early phases of prediabetes, warrants further investigation.     

预防性应用吡格列酮改善胰岛素抵抗的脂肪内分泌机制

目的探讨吡格列酮改善胰岛素抵抗过程中脂肪内分泌功能的改变。方法45只W istar雄性大鼠随机分为对照组、胰岛素抵抗组和吡格列酮组。胰岛素抵抗动物模型成功建立后,分析各组抵抗素、脂联素和脂联素受体的表达。结果与胰岛素抵抗组比较,吡格列酮组大鼠的体质量、空腹血糖、游离脂肪酸差异不明显,但胰岛素、胰岛素抵抗指数、葡萄糖耐量和胰岛素耐量明显改善（P〈0.01）,脂联素表达明显增高（P〈0.05）。结论脂肪内分泌功能紊乱在高脂诱导胰岛素抵抗的发生中起着重要的作用,预防性应用吡格列酮可明显延缓大鼠胰岛素抵抗的发生,改善脂肪内分泌功能。