胰岛素抵抗与动脉粥样硬化

随着经济高速发展 ,包括我国在内的发展中国家心脑血管病、高血压、糖尿病、肥胖病、血脂异常已成为人类致死、致残的主要原因 ,而动脉粥样硬化是这些疾病致病机制中的核心问题 ,胰岛素抵抗 (ＩＲ)与动脉粥样硬化之间的内在联系已逐层显露 ,实质上 ,ＩＲ是众多代谢性异常和心血管疾病的原始动因和致病基础。近年研究表明 ,血管内皮细胞本身也可产生ＩＲ ,引起血流减少、外周血管阻力增加。ＩＲ不仅表现为肌肉、肝、脂肪细胞对糖摄取、利用下降 ,引起血糖升高 ,同时也可引起血脂紊乱、高血压和动脉粥样硬化。英国前瞻性糖尿病研究(ＵＫＰＤＳ…     

C肽与颈动脉内膜中层厚度的相关性研究

目的通过测定不同C肽（C-P）水平患者的颈动脉内膜中层厚度（IMT）,研究C-P与动脉粥样硬化的关系。方法以正常糖代谢、糖耐量减低及2型糖尿病病程小于5年的112例患者为研究对象,根据C-P三分位间距分为A、B、C组,应用彩色多普勒超声仪测定颈动脉IMT,并测量腰围、体质指数、血糖、血脂、尿酸等,各组间进行单因素方差分析,差异有统计学意义的指标与C-P水平进行Pearson相关分析,同时记录用药情况进行行×列x^2检验。结果各组间IMT的差异有统计学意义（P〈0．05）,B组和C组高于A组（P〈0．05）;同时腰围、体质指数、尿酸、甘油三酯存在差异且与C-P呈正相关;三组间高密度脂蛋白胆固醇差异有统计学意义（P〈0．05）,C组明显低于A组（P〈0．05）,B组与A组无明显统计学差异（P〉0．05）,且HDL-C与C-P呈负相关。结论随着C-P水平的升高IMT增加,在胰岛素抵抗及病程小于5年的2型糖尿病中升高的C-P可能反映动脉粥样硬化的发生。     

血清真胰岛素、C肽水平及肥胖与老年高血压的关系

目的探讨血清真胰岛素、C肽水平及肥胖与老年高血压的关系。方法将35例老年高血压非糖尿病患者按体重指数分为肥胖组(n=20)与非肥胖组(n=15),以20例老年健康者作为对照组,采用微粒子化学发光法测定空腹血清真胰岛素、C肽,以稳态模型评估法评价胰岛素抵抗(HOMA-IR)和胰岛β细胞功能指数(HOMA-islet)。结果肥胖组和非肥胖组血清真胰岛素、C肽水平及HOMA-IR和HOMA-islet指数均高于健康对照组。相关性分析显示血清真胰岛素与C肽、FPG、LDL-C、血尿酸水平呈正相关关系。结论老年高血压非糖尿病患者,特别是伴有肥胖者,血清真胰岛素、C肽、TC、LDL-C及血UA水平较健康老年人明显增高,存在IR、高胰岛素血症及代偿性胰岛β细胞功能增高。老年高血压非糖尿病患者血清真胰岛素水平与C肽、FPG、LDL-C、血UA呈明显正相关。     

空腹C肽质量浓度与胰岛素抵抗相关性研究

目的比较C肽和胰岛素在评估胰岛素抵抗性(IR)的差异。方法依口服糖耐量试验将2003年3月至2004年3月中国医科大学附属第二医院门诊及周围社区的44例汉族人分为正常糖耐量(NGT)组、孤立空腹血糖受损(I-IFG)组、孤立糖耐量受损(I-IGT)组,联合糖耐量受损(C-IGT)组。观察葡萄糖钳夹试验测定的IR指标(葡萄糖输注速率,GIR)和其空腹胰岛素、C肽的关系。结果I-IFG、I-IGT、C-IGT组的GIR明显低于NGT(P<0.01),但各组的空腹C肽浓度差异无显著性。各组的胰岛素作用指数(IAI)、稳态模式评估法指数(HOMA-IR)、空腹胰岛素衍生的IR指标定量胰岛素敏感性检测指数(QUICKI)与GIR均呈良好相关(P<0.05),相关系数在0.766~0.498之间,但空腹C肽替代胰岛素后的IR指标与GIR无明显相关,相关系数在0.394~0.042之间(P>0.05)。结论空腹C肽质量浓度和胰岛素抵抗程度没有相关性。     

空腹C肽质量浓度与胰岛素抵抗相关性研究

目的比较C肽和胰岛素在评估胰岛素抵抗性（IR）的差异。方法依口服糖耐量试验将2003年3月至2004年3月中国医科大学附属第二医院门诊及周围社区的44例汉族人分为正常糖耐量（NGT）组、孤立空腹血糖受损（I—IFG）组、孤立糖耐量受损（I—IGT）组，联合糖耐量受损（C—IGT）组。观察葡萄糖钳夹试验测定的IR指标（葡萄糖输注速率，GIR）和其空腹胰岛素、C肽的关系。结果I—IFG、I—IGT、C—IGT组的GIR明显低于NGT（P〈0．01），但各组的空腹C肽浓度差异无显著性。各组的胰岛素作用指数（IAI）、稳态模式评估法指数（HOMA—IR）、空腹胰岛素衍生的IR指标定量胰岛素敏感性检测指数（QUICKI）与GIR均呈良好相关（P〈0．05），相关系数在0.766～0．498之间，但空腹C肽替代胰岛索后的IR指标与GIR无明显相关，相关系数在0．394～0．042之间（P〉0．05）。结论空腹C肽质量浓度和胰岛素抵抗程度没有相关性。     

脂联素与胰岛素抵抗、动脉粥样硬化及心血管疾病

脂联素是脂肪细胞特异性细胞因子,其血浆水平与胰岛素抵抗、肥胖症、2型糖尿病以及动脉硬化疾病的发病有关。血浆脂联素在血管损伤的早期和晚期均具有终止炎症反应,阻止动脉粥样硬化发生的作用。此外,脂联素还可通过增强胰岛素的敏感性,纠正高胰岛素和高糖血症所致的高血压;通过调节代谢降低导致心血管疾病的多种危险因素。     

非酒精性脂肪性肝病与动脉粥样硬化之间关系的研究进展

非酒精性脂肪性肝病( NAFLD)常与肥胖、糖尿病、高血脂、高血压以及代谢综合征合并存在,认为是代谢综合征的肝脏表现。NAFLD的患病率约20％～30％,在2型糖尿病人群中NAFLD患病率更高。NAFLD与心血管疾病(CVD)关系密切,NAFLD患者的主要死亡原因是CVD。NAFLD和动脉粥样硬化(AS)关系密切,其机制可能涉及氧化应激、炎症反应、脂代谢紊乱、脂肪激素水平的变化和胰岛素抵抗等方面。本文就NAFLD和AS间的关系以及可能机制进行综述。     

ApoCⅢ与动脉粥样硬化性心血管疾病相关性的研究进展

载脂蛋白CⅢ(Apo CⅢ)不仅通过脂代谢紊乱参与动脉粥样硬化(As)等心血管疾病的发生、发展,近年来还作为一个独立的促炎和致As角色被重新认识,不仅临床研究发现Apo CⅢ与心血管疾病相关,其与心血管疾病的相关细胞效应也在基础研究中得到证实。值得庆幸的是,除了传统治疗策略,如生活方式的改变和降脂药物治疗,专门针对Apo CⅢ-m RNA的反义寡核苷酸药物(ASO)开启了降低Apo CⅢ及心血管疾病治疗的新时代。文章就有关Apo CⅢ的临床意义及未来治疗方向进行以下综述。     

C肽研究进展

Ｃ肽是胰岛素原的裂解产物，长期以来一直认为它没有生物功能，近年来人们发现Ｃ肽对Ⅰ型糖尿病有一定的治疗作用。本文就Ｃ肽对ＩＤＤＭ患者的肾病，眼底病，神经病及糖代谢紊乱的治疗作用及可能机制作一简单复习。     

炎性体在动脉粥样硬化等心血管疾病中的作用及机制

炎性体是一个识别多种固有免疫系统激活物的多蛋白复合体,它可以促进白细胞介素1β（IL-1β）和白细胞介素18（IL-18）等炎症因子的生成,参与多种心血管疾病（CVD）的炎症反应,如动脉粥样硬化、缺血性心脏病、缺血再灌注损伤、高血压和心肌病变等。炎性体激活及其下游产物生成的调控机制已成为CVD研究领域新的热点。此外,炎性体作为固有免疫系统的一部分,为CVD治疗提供了新的药物靶点。     

基质金属蛋白酶8在动脉粥样硬化中的研究进展

基质金属蛋白酶8(matrix metalloproteinase-8,MMP-8)是基质金属蛋白酶家族的重要成员之一。最新研究发现,MMP-8通过降解胶原蛋白及其他活性物质,调节内皮细胞、平滑肌细胞、中性粒细胞及干细胞的功能,促进了动脉粥样硬化斑块的发生发展及不稳定性。MMP-8与冠心病的发生及预后密切相关,其基因多态性与动脉粥样硬化的发生和发展紧密联系。本文就MMP-8与动脉粥样硬化疾病相关的最新研究进展进行综述,讨论MMP-8在动脉粥样硬化中的作用机制,为动脉粥样硬化寻找生物标志物及潜在治疗靶点提供思路。     

慢性肾脏病患者动脉粥样硬化危险因素的研究进展

心血管疾病是慢性肾脏病患者最常见的并发症,而动脉粥样硬化是心血管疾病最主要的病因。对动脉粥样硬化程度及其相关危险因素进行控制,可以缓解慢性肾脏病患者的病情,降低其死亡率,在临床上有重要意义。     

Mathematical modelling of changes in circulating insulin and C-peptide concentrations

Summary A simple mathematical model is proposed to assess the validity of methods currently used in clinical investigation to detect short-term or long-term alterations in insulin and/or C-peptide clearance. This model draws attention to unwarranted conclusions which resulted from the analysis of insulin and C-peptide plasma concentrations.     

非糖尿病腹膜透析患者胰岛素抵抗与颈动脉粥样硬化的相关性

目的探讨非糖尿病腹膜透析患者胰岛素抵抗与动脉粥样硬化的关系。方法选择非糖尿病腹膜透析的成年患者64例,对其临床资料包括胰岛素抵抗指数(HOMA-IR)进行分析。采用高分辨二维超声对双侧颈总动脉内膜中膜厚度(IMT)及颈动脉粥样斑块进行测量。按IMT厚度及有无斑块分为两组:无颈动脉硬化组(IMT1.0 mm)和颈动脉硬化组(IMT≥1.0 mm和/或已发现有颈动脉斑块)。结果颈动脉硬化组餐后2 h血糖(2h PBG)、低密度脂蛋白胆固醇(LDLC)、高敏C反应蛋白(hs-CRP)、甘油三酯(TG)和HOMA-IR高于无颈动脉硬化组(P0.05),而血浆白蛋白则低于无颈动脉硬化组(P0.01);颈动脉硬化组胰岛素抵抗患者占53.49%,而无颈动脉硬化组胰岛素抵抗患者仅占4.76%(P0.01)。相关分析显示非糖尿病腹膜透析患者动脉硬化与年龄、2h PBG、LDLC、hs-CRP、TG和HOMA-IR呈正相关(r=0.375、0.373、0.420、0.345、0.351、0.458,P0.05);Logistic回归分析发现,年龄、HOMA-IR、2h PBG、hs-CRP是非糖尿病腹膜透析患者发生动脉粥样硬化的危险因素。结论在非糖尿病腹膜透析患者中HOMA-IR水平与颈动脉粥样硬化正相关,HOMA-IR可能促进了动脉粥样硬化的发生。     

Haemolysis affects insulin but not C-peptide immunoassay

Summary Venous blood was taken at the end of a glucose infusion test in 19 individuals and divided into four aliquots, 3 of which were variably haemolysed by repeated passage through a 23-gauge needle to simulate traumatic venepuncture. Plasma insulin (measured by both a charcoal separation and a double-antibody method), C-peptide, and haemoglobin were measured in each aliquot, and haemolysis was also assessed visibly. A significant loss of immuno-assayable plasma insulin was found in samples with only a trace of visible haemolysis, with up to 90% lost in severely haemolysed samples. Plasma C-peptide was unaffected by haemolysis. This represents an additional advantage for the use of plasma C-peptide in assessing insulin secretion.     

A comparison of serum C-peptide response to intravenous glucagon, and urine C-peptide, as indexes of insulin dependence

Serum C-peptide (SCPR) at fasting and after intravenous injection of glucagon was evaluated in diabetic patients with various degrees of insulin dependence, and compared with 24 h urine C-peptide (UCPR). Fasting SCPR did not differ between healthy subjects and sulfonylurea-treated patients (SU) who were considered to have definite non-insulin-dependent diabetes (NIDDM); but was significantly lower in patients with insulin-dependent diabetes (IDDM) (0.24 +/- 0.10 ng/ml in IDDM vs. 1.43 +/- 0.61 ng/ml in SU, P less than 0.001). SCPR reached a peak at 6 min after glucagon injection, except for the IDDM group. The SCPR response at 6 min after 1 mg glucagon injection was significantly lower in the SU (NIDDM) group than in the normal group (2.86 +/- 1.21 v. 4.69 +/- 1.47 ng/ml, P less than 0.001). In the IDDM group, there was no increase of SCPR after glucagon injection. Among diabetic patients, SCPR response to glucagon correlated positively to the amounts of UCPR (P less than 0.001). By analysis of the distribution patterns of SCPR response to intravenous glucagon, SCPR of 1.0 ng/ml and the increment of SCPR of 0.5 ng/ml at 6 min are to be used as cut-off points to differentiate IDDM and NIDDM. These values correspond roughly to the UCPR values below 20 micrograms/day and above 30 micrograms/day, which we previously proposed as indexes to differentiate insulin-dependent and non-insulin-dependent diabetes.     

高胰岛素血症与动脉粥样硬化研究现状与进展

糖尿病血管病变是糖尿病的一个最常见的慢性并发症,可累及全身的大血管及微血管,其中大血管病变导致的心脑血管疾病是2型糖尿病患者首要的死亡原因,约占2型糖尿病死因的50％.糖尿病合并大血管病变是目前糖尿病并发症研究的热点,但其具体机制至今尚未完全阐述清楚.本文综述了高胰岛素血症与动脉粥样硬化研究现状与进展,并探讨其引发动脉粥样硬化的可能机制.     

Association of C-peptide with diabetic vascular complications in type 2 diabetes

AimFasting serum C-peptide is a biomarker of insulin production and insulin resistance, but its association with vascular complications in type 2 diabetes mellitus (T2DM) has never been fully elucidated. This study aimed to investigate whether C-peptide is associated with cardiovascular disease (CVD) and diabetic retinopathy (DR).MethodsA total of 4793 diabetes patients were enrolled from seven communities in Shanghai, China, in 2018. CVD was defined as a self-reported combination of previous diagnoses, including coronary heart disease, myocardial infarction and stroke. DR was examined using fundus photographs. Logistic regression analyses were performed, and multiple imputed data were used to obtain stabilized estimates.ResultsPrevalence of CVD increased with increasing C-peptide levels (Q1, Q2, Q3 and Q4: 33%, 34%, 37% and 44%, respectively; P_{for trend} < 0.001), whereas DR prevalence decreased with increasing C-peptide quartiles (Q1, Q2, Q3 and Q4: 21%, 19%, 15% and 12%, respectively; P_{for trend} < 0.001). On logistic regression analysis, C-peptide levels were significantly associated with CVD prevalence (1.27, 95% CI: 1.13–1.42; P < 0.001) and C-peptide quartiles (Q1: reference; Q2: 1.31, 95% CI: 1.00–1.70; Q3: 1.53, 95% CI: 1.16–2.01; Q4: 1.76, 95% CI: 1.32–2.34; P_{for trend} < 0.001). Given the interaction between C-peptide and BMI and the association between C-peptide and CVD (P_{for interaction} = 0.015), study participants were divided into two subgroups based on BMI which revealed that the association persisted despite different BMI statuses. However, DR prevalence decreased with increasing C-peptide levels (0.73, 95% CI: 0.62–0.86; P < 0.001) and quartiles (Q1: reference; Q2: 1.00, 95% CI: 0.76–1.33; Q3: 0.69, 95% CI: 0.50–0.94; Q4: 0.51, 95% CI: 0.36–0.72; P_{for trend} < 0.001).ConclusionC-peptide was positively associated with CVD, but inversely associated with DR progression. The association between C-peptide and CVD could be due to associated metabolic risk factors.