原发性高血压患者胰岛素抵抗指数、瘦素、脂蛋白水平的变化及意义

目的通过检测原发性高血压（EH）患者胰岛素抵抗（IR）指数及血清瘦素（Leptin）、脂蛋白水平变化,探讨EH患者IR指数与血清Leptin、脂蛋白的相关性及其临床价值。方法采用ELISA法测定EH患者及健康对照者的血清Leptin,测定IR指数（采用稳态模式评估公式HOMA-IR计算）及外周血Leptin、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平,并在不同分期及是否合并IR患者之间进行比较。结果 EH患者IR指数、血清Leptin及LDL-C水平均显著高于健康对照者,HDL-C水平显著低于健康对照者（P均〈0.05）;EHⅡ期与EHⅠ期比较,IR指数、血清Leptin及LDL-C水平均显著增高,HDL-C水平显著降低（P均〈0.05）;EH-IR者与EH非IR者比较,血清Leptin及LDL-C水平均显著增高,HDL-C水平显著降低（P均〈0.05）。EH患者IR指数与外周血Leptin、LDL-C水平呈显著正相关（r=0.572、0.416,P均〈0.05）,与HDL-C水平呈显著负相关（r=-0.313,P〈0.05）;EH患者外周血Leptin水平与LDL-C水平呈显著正相关（r=0.501,P〈0.05）,与HDL-C水平呈显著负相关（r=-0.315,P〈0.05）。结论 EH患者体内存在IR及Leptin、HDL-C、LDL-C的异常表达,其变化与血压分级有关,IR指数、Leptin与脂蛋白具有相关性。IR指数、Leptin、LDL-C及HDL-C可作为EH的辅助诊断及治疗的指标之一。     

脂肪细胞因子与非酒精性脂肪性肝病胰岛素抵抗的初步探讨

目的探讨视黄醇结合蛋白4(RBP-4)及网膜素与非酒精性脂肪性肝病(NAFLD)患者胰岛素抵抗的关系。方法选择NAFLD患者50例(NAFLD组),无NAFLD患者50例(对照组)。测定2组空腹血糖、空腹胰岛素、HDL-C、LDL-C、TC、TG、天冬氨酸转氨酶、丙氨酸转氨酶、RBP-4及网膜素,同时计算体重指数、胰岛素抵抗指数,并进行多元逐步回归分析。结果 NAFLD组体重指数、丙氨酸转氨酶、TG、空腹胰岛素、胰岛素抵抗指数及RBP-4水平明显高于对照组,HDL-C、网膜素水平明显低于对照组(P<0.05,P<0.01)。Pearson相关分析,NAFLD组胰岛素抵抗指数与年龄、血压、体重指数、空腹血糖、空腹胰岛素、TC、TG、LDL-C、RBP-4呈正相关,与HDL-C、网膜素呈负相关(P<0.05,P<0.01)。多元线性逐步回归结果进入回归方程的有RBP-4、TG、体重指数、网膜素(P<0.05,P<0.01)。结论 RBP-4和网膜素与NAFLD患者胰岛素抵抗发生、发展有关。     

妊娠期糖尿病胰岛素抵抗与铁蛋白和游离脂肪酸的相关性研究

目的探讨妊娠期糖尿病(GDM)孕妇胰岛素抵抗(IR)与铁蛋白(SF)和游离脂肪酸(FFA)的关系。方法 2011—2013年,按照随机原则选择在我院就诊的GDM孕妇71例为GDM组,正常孕妇50例为正常孕妇组,体检健康且未孕女性50例为正常非孕组。检测3组受试者血清SF、FFA、空腹血糖(FBG)及空腹胰岛素(Fins)水平,计算胰岛素抵抗指数(HOMA-IR)。结果正常非孕组、正常孕妇组及GDM组血清SF水平分别为(119.57±22.04)μg/L、(197.81±46.32)μg/L、(388.79±91.67)μg/L,差异有统计学意义(F=57.543,P0.01);GDM组血清SF水平高于正常孕妇组和正常非孕组,正常孕妇组高于正常非孕组(P0.01)。正常非孕组、正常孕妇组及GDM组血清FFA水平分别为(0.43±0.18)mmol/L、(0.67±0.14)mmol/L、(1.03±0.21)mmol/L,差异有统计学意义(F=37.619,P0.01);GDM组血清FFA水平高于正常孕妇组和正常非孕组,正常孕妇组高于正常非孕组(P0.01)。正常非孕组、正常孕妇组及GDM组HOMA-IR分别为(1.83±0.45)、(2.92±0.87)、(3.94±1.02),差异有统计学意义(F=45.071,P0.01);GDM组HOMA-IR高于正常孕妇组和正常非孕组,正常孕妇组高于正常非孕组(P0.01)。Pearson相关分析结果显示,血清SF水平(r=0.832)、血清FFA水平(r=0.759)均与HOMA-IR呈正相关(P0.01);血清SF水平与血清FFA水平呈正相关(r=0.893,P0.01)。结论 GDM孕妇存在IR及高铁蛋白血症、高游离脂肪酸血症,IR程度与血清SF、FFA水平相关,在GDM的早期干预中应重视SF和FFA的调控。     

OxLDL对动脉粥样硬化血栓作用研究的进展

动脉粥样硬化(AS)是心血管疾病的主要病理生理基础,也是导致心血管疾病死亡的主要病因.氧化低密度脂蛋白(oxLDL)在AS斑块的发生发展和AS血栓的形成中起重要作用.OxLDL及其组分通过多种途径直接或间接促进促凝血活动及AS血栓的形成.本文就oxLDL及其组分对促进血栓形成的相关细胞和通路的影响作一综述.     

A型胰岛素抵抗综合征胰岛素分泌变化的七年随访

目的 对1例A型胰岛素抵抗综合征患者随访7年,观察血糖及胰岛素分泌变化.方法 患者初诊年龄16岁,分别于基线、第3、6、7年进行临床随访,观察患者延长口服葡萄糖耐量试验(OGTT)及同步胰岛素、C肽的分泌,比较各随访年血糖、胰岛素、C肽曲线下面积(AUC);比较基线与第7年静脉葡萄糖耐量试验急性胰岛素分泌反应(AIR)的变化;将延长OGTT各时间点胰岛素分泌速率用体表面积标化后,与相应血浆葡萄糖作出剂量反应曲线,比较各随访年胰岛β细胞对葡萄糖的分泌反应.结果 患者7年间糖化血红蛋白均维持正常(4.6%～5.5%),葡萄糖AUC无增加,胰岛素及C肽AUC呈下降趋势;第7年胰岛素AIR较基线时减少56%;胰岛β细胞对葡萄糖的分泌反应随时间推移而呈下降趋势.结论 随着青春期结束,该患者总体胰岛素分泌水平呈下降趋势,因不伴血糖的进行性恶化,考虑为青春期过后生理性胰岛素敏感性恢复,而非真正意义的胰岛β细胞分泌功能衰退.

Abstract：

Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.     

支链氨基酸代谢与胰岛素抵抗及2型糖尿病研究进展

<正>胰岛素是维持机体内葡萄糖稳态的最主要激素,组织细胞保持对胰岛素的敏感性是维持健康新陈代谢的重要因素。目前,诱发胰岛素抵抗的具体机制并未研究清楚。支链氨基酸(branched-chain amino acid,BCAA)属于必需氨基酸,通过直接和间接的方式作用于代谢信号通路。尽管有报道称BCAA有益于健康的新陈代谢,然而,血浆BCAA水平升高与胰岛素抵抗、代谢紊乱及2型糖尿病密切相关。我们就     

经典1型糖尿病患者胰岛素抵抗的高胰岛素正葡萄糖钳夹研究

目的 应用高胰岛素正葡萄糖钳夹技术评价1 型糖尿病(T1DM)患者胰岛素抵抗程度.方法 选择新诊断T1DM患者8例,初诊未治2型糖尿病(T2DM)患者8例,均经2周胰岛素强化治疗后进行高胰岛素正葡萄糖钳夹检测胰岛素敏感性指数(ISI),并与正常糖耐量志愿者10例进行比较.结果 T1DM组的年龄、BMI、空腹胰岛素(FIns)及空腹C-肽等各项参数显著低于正常对照组(P＜0.05),而腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、TC、TG、LDI-C、HDL-C均与正常对照组差异无统计学意义.T1DM组与T2DM组比较,年龄、BMI、WHR、FIns、空腹C-肽、SBP、TC、TG均显著低于T2DM组(P＜0.05).正常对照组、T1DM组、T2DM组ISI分别为12.83±1.09、9.95±0.50、3.80±0.20,3组间ISI差异有统计学意义(P＜0.05).结论 高胰岛素正葡萄糖钳夹检测结果显示,TIDM患者的ISI显著低于正常人,但高于T2DM患者.     

冠心病患者冠状动脉循环氧化低密度脂蛋白水平与内皮损伤的关系

目的探讨冠心病患者氧化低密度脂蛋白(ox-LDL)变化与冠状动脉(冠脉)内皮损伤及相关临床表现的关系。方法54例冠心病患者均经冠脉造影证实有明显冠脉狭窄,测定其冠状窦和外周血中ox-LDL、一氧化氮(NO)及循环内皮细胞(CEC)数量,分为不稳定型心绞痛(UA)组和稳定型心绞痛(SA)组,比较两组与正常对照组(20例)间相同和不同部位之间指标的差异。结果UA组、SA组患者冠状窦血中NO含量较对照组明显降低,ox-LDL和CEC均明显增高。冠状窦血中NO含量均明显低于外周血,ox-LDL和CEC均明显高于外周血。对照组冠状窦与外周血相比三项指标均未见明显差别。结论冠心病患者冠脉局部ox-LDL升高与冠脉内皮损伤相关,并与冠心病病情严重程度一致,可能参与了冠心病病情恶化以及急性冠脉事件的发生。     

丙型肝炎病毒所致胰岛素抵抗相关分子的研究进展

慢性丙型肝炎（CHC）患者易发生胰岛素抵抗（IR）。实验表明CHC相关IR不但与肝脂肪变性、肝纤维化、食管静脉曲张、肝细胞肝癌、肝癌扩散及一些肝外临床表现有关,还降低了以干扰素（IFN）联合利巴韦林为基础的抗病毒治疗早期及持续应答率。已有较多实验利用各种模型分析了丙型肝炎病毒（CHV）导致IR的发病机制,现对当前研究已知的几个分子及其机制做一综述。     

低密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值与急性冠脉综合征及冠脉病变程度相关性研究

目的探讨血清低密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值（LDL-C/HDL-C值）与急性冠脉综合征（ACS）以及冠状动脉病变程度之间的关系。方法对我院冠状动脉造影118例患者临床资料进行回顾分析。结果 ACS患者的LDL-C/HDL-C值与冠状动脉病变的程度具有良好的相关性,两级之间的LDL-C/HDL-C值差异有统计学意义（P〈0.05）结论ACS患者LDL-C/HDL-C值可作为判断ACS的严重程度的生化指标之一。     

胰岛素在阿尔茨海默病发病中的作用

许多研究表明 ,胰岛素水平及其敏感性异常与阿尔茨海默病的发病机制及其临床表现相关 ,提示通过提高胰岛素的水平和 (或 )敏感性有助于该病的治疗。     

吉非罗齐对高甘油三酯合并低高密度脂蛋白患者胰岛素敏感性的影响

目的 :观察高甘油三酯 (TG)合并低高密度脂蛋白胆固醇 (HDL- C)患者在服用吉非罗齐治疗的同时对胰岛素敏感性的影响。方法 :测定 46例高 TG合并低 HDL- C血症而不伴有高血压及冠心病的患者应用吉非罗齐治疗 12周前后及 40例健康人 (正常对照组 )血 TG、HDL- C、血糖 (SG)及胰岛素 (INS)变化 ,并计算胰岛素敏感性指数 (ISI)。结果 :吉非罗齐治疗前 ,治疗组 INS显著升高 (P <0 .0 1) ,ISI明显降低 (P <0 .0 1) ,两组 SG无明显差异 (P >0 .0 5 )。吉非罗齐治疗 12周后 ,治疗组 INS明显下降 (P <0 .0 5 ) ,ISI显著增高 (P <0 .0 5 ) ,TG明显降低 (P <0 .0 1) ,HDL - C明显增高 (P <0 .0 5 )。结论 :高 TG合并低 HDL - C血症患者存在胰岛素抵抗 (ISR) ,吉非罗齐治疗后 ,在改善血脂代谢的同时 ,也改善机体 ISR     

骨骼肌线粒体异常在胰岛素抵抗形成中的作用

胰岛素抵抗及其相关疾病与机体的各种代谢异常密切相关.线粒体是调控代谢通路的重要细胞器,其功能的改变可对机体代谢产生极大影响.骨骼肌是胰岛素刺激葡萄糖利用的主要器官,同时也是富含线粒体和依赖氧化磷酸化供能的组织.因此,骨骼肌线粒体异常可能与胰岛素抵抗高度相关,其机制有待阐明.     

Liver plays a central role in asymmetric dimethylargininemediated organ injury

Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.     

Metabolism of high density lipoprotein apolipoprotein A-I and cholesteryl ester in insulin resistant dog: a stable isotope study

AIMS: In reverse cholesterol transport (RCT), hepatic Scavenger Receptor class B type I (SR-BI) plays an important role by mediating the selective uptake of high-density lipoprotein cholesteryl ester (HDL-CE). However, little is known about this antiatherogenic mechanism in insulin resistance. HDL-CE selective uptake represents the main process for HDL-CE turnover in dog, a species lacking cholesteryl ester transfer protein activity. We therefore investigate the effects of diet induced insulin resistance on RCT. METHODS: Five beagle dogs, in healthy and insulin resistant states, underwent a primed constant infusion of [1,2(13)C(2)]acetate and [5,5,5-(2)H(3)]leucine, as labelled precursors of CE and apolipoprotein (apo) A-I, respectively. Data were analysed using modelling methods. RESULTS: HDL-apo A-I concentration did not change in insulin resistant state but apo A-I absolute production rate (APR) and fractional catabolic rate (FCR) were both higher (2.2- and 2.4-fold, respectively, p < 0.05). HDL-CE levels were lower (1.2-fold, p < 0.05). HDL-CE APR and FCR were both lower (2.3- and 2-fold, respectively, p < 0.05), as well as selective uptake (2.6-fold, p < 0.05). CONCLUSIONS: Lower HDL-CE selective uptake suggests that RCT is impaired in obese insulin resistant dog.     

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.     

糖尿病病合并高血压或高脂血症的胰岛素敏感性探讨

目的:探讨2型糖尿病患者在合并高血压或高脂血症时的胰岛索抵抗(IR)。方法:采用胰岛素敏感指数(空腹血糖、空腹胰岛素乘积的倒数),对37例糖尿病合并高血压组和31例糖尿病合并高脂血症组及63例单纯糖尿病组进行比较。结果:糖尿病合并高血压组胰岛素敏感指数大于单纯糖尿病组(P<0.05)。结论:本研究提示糖尿病合并高血压的患着比未合并高血压的患者存在着更为显著的胰岛素抵抗。     

胰岛素抵抗高血压大鼠血清瘦素水平与胰岛素抵抗的关系

目的:探讨胰岛素抵抗高血压大鼠血清瘦素水平与胰岛素抵抗的关系。方法:以高果糖饲料喂养雄性SD大鼠复制胰岛素抵抗高血压大鼠模型,测定其收缩压(SBP)、空腹皿糖(FBG)、空腹血清胰岛素(FINS)和瘦素(LP)水平,用稳态模型(HOMA)评估胰岛素抵抗(IR),分析血清瘦素水平与胰岛素抵抗的相关性及与血压等其他指标的关系。结果:与对照组相比,模型鼠组SBP、FINS、HOMA-IR明显升高(P<0.01,P<0.01,P<0.05),FBG无明显变化(P>0.05);LP显著升高(P<0.05);模型鼠组的LP与FINS、SBP、HOMA-IR呈显著正相关(P<0.05)。结论:高果糖饲料喂养SD大鼠能形成胰岛素抵抗及高血压,并有高瘦素血症。瘦素与胰岛素抵抗的形成关系密切。     

不同胰岛素抵抗状态的初诊2型糖尿病患者短期胰岛素强化疗效观察

对62例不同胰岛素抵抗状态的初诊2型糖尿病患者进行2周胰岛素强化治疗,结果显示胰岛素强化治疗降糖效果确切,能改善β细胞功能,但有明显胰岛素抵抗的患者治疗效果欠佳。     

胰岛素抵抗高血压大鼠心肌纤维化的研究

目的　探讨胰岛素抵抗时心肌纤维化形成的可能机制。方法　以高蔗糖喂养形成的胰岛素抵抗高血压大鼠(IRHR)和正常对照 SD大鼠为研究对象 ,观察其心肌纤维化指标 (心肌组织羟脯氨酸含量及胶原容积分数 ) ,并进行相关性分析及形态学观察。结果　 IRHR组血压、血清胰岛素、左心室相对重量、心肌组织羟脯氨酸含量及胶原容积分数均明显高于对照组 ,其胰岛素敏感指数明显降低。形态学观察发现其心肌间质胶原纤维明显增多。相关分析发现左心室相对重量、心肌组织羟脯氨酸含量及胶原容积分数均与血清胰岛素呈明显正相关 ,与胰岛素敏感指数呈负相关。结论　高蔗糖饲料喂养 SD大鼠可以形成胰岛素抵抗和高血压 ,其心肌纤维化的形成与胰岛素抵抗、代偿性高胰岛素血症有关 ,胰岛素抵抗可能是高血压心肌纤维化发生的机制之一