内脏脂肪素与肥胖、胰岛素抵抗

内脏脂肪素（visfatin）是新近发现的主要由内脏脂肪组织表达的一种脂肪细胞因子，与内脏脂肪量呈正相关，在内脏脂肪组织丰度极高，在肥胖的发展过程中表达亦升高。内脏脂肪素具有Ins模拟效应，能降低糖尿病小鼠的血浆葡萄糖水平，并与胰岛素受体（InsR）相结合，通过Ins信号传导．途径的活化发挥积极的作用。其发现为肥胖和胰岛素抵抗（IR）的研究提供了新的方向。现就内脏脂肪素的分泌、调控以及与Ins的联系，与IR之间的关系及其可能的机制作一综述。     

内脏脂肪素与糖尿病及胰岛素抵抗的关系研究进展

脂肪组织一直被认为只是贮备能量的终末分化器官.近年研究证实脂肪组织可以分泌20多种具有生物活性的脂肪细胞因子如瘦素(leptin)、抵抗素(resistin)、脂联素(adiponectin)、网膜素(omentin)等等[1].目前人们已认识到脂肪组织还具有旺盛的内分泌功能[2].2005年1月日本大阪大学的Fukuhara 等[3]利用差异显示方法又发现了一种新的由内脏脂肪组织分泌的脂肪细胞因子,命名为内脏脂肪素(visfatin,VFN).近两年来,人们对VFN的研究取得了一些新的成果.     

2型糖尿病患者血清内脏脂肪素水平及其影响因素

目的探讨2型糖尿病（T2DM）患者血清内脏脂肪素水平的变化及其影响因素。方法选择T2DM患者47例,健康对照（NGT）35名,测定受试者一般临床及生化指标,酶联免疫吸附法（ELISA）测定空腹血清内脏脂肪素水平,并分析各指标的关系。结果与NGT组相比,T2DM组内脏脂肪素水平明显升高（70．43±20．710g／Lw98．48±22．37μg／L,P〈0．01）;相关性研究显示,内脏脂肪素水平与腰围、臀围、腰臀比、空腹血糖、HbA1c均呈正相关;多元线性逐步回归分析表明,腰围和空腹血糖是影响内脏脂肪素水平的独立相关因素。结论T2DM患者空腹血清内脏脂肪素水平升高,血清内脏脂肪素可能在T2DM发生发展中起一定的作用。     

2型糖尿病伴冠心病患者血浆内脏脂肪素水平的观察

目的探讨内脏脂肪素与血糖、胰岛素抵抗及冠状动脉粥样硬化之间的关系。方法将冠心病患者分为2型糖尿病冠心病组、单纯冠心病组,并以30名健康人群作为对照组,测定空腹血浆内脏脂肪索等。结果2型糖尿病冠心病组、单纯冠心病组的血浆内脏脂肪素水平均显著高于对照组（P均〈0．01）。结论血浆内脏脂肪素水平与血糖、胰岛素抵抗及冠状动脉粥样硬化相关,但不是影响冠状动脉粥样硬化的独立相关因素。     

脂联素与瘦素的比值和2型糖尿病胰岛素抵抗的相关性

在160例2型糖尿病患者分析脂联素与瘦素的比值(A/L)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)和胰岛素抵抗参数的相关性.结果 显示,在两性患者中,A/L和体重指数、腰臀比、甘油三酯、高密度脂蛋白胆固醇均显著相关.当空腹血糖逐渐升高时,A/L与胰岛素抵抗参数仍然相关,而HOMA-IR不再相关,提示A/L相对于脂联素、瘦素、HOMA-IR是一个较好评估胰岛素抵抗的指标.     

2型糖尿病患者内脏素水平与胰岛素抵抗、胰岛β细胞功能之间的关系

目的 探讨2型糖尿病患者内脏素水平变化及与胰岛抵抗和胰岛B细胞功能之间的关系.方法 检测了2型糖尿病患者95例和正常对照组54例内脏素、血脂、血糖和空腹胰岛素(FINS)水平,并评价了颈总动脉内膜中层厚度(IMT).采用稳态模式(HOMA)评价胰岛素抵抗和胰岛β细胞功能.结果 2型糖尿病组胰岛素抵抗指数(HOMA-IR)、颈动脉IMT和内脏素水平高于对照组,胰岛β细胞功能指数(HOMA-β)水平低于对照组(P<0.05).Spearman相关性分析显示,内脏素与空腹血糖(r＝0.496,P＝0.000)和HOMA-IR(r＝-0.380,P＝0.000)呈正相关;与HOMA-β(r＝-0.355,P＝0.000)呈负相关.多元逐步回归分析显示,内脏素与空腹血糖呈独立正相关(P＝0.000).结论 2型糖尿病患者内脏素水平升高,内脏素可能与胰岛素抵抗和胰岛β细胞功能损害有一定相关性.     

2型糖尿病患者应用甘精胰岛素治疗前后内脏脂肪素水平的变化

目的探讨应用甘精胰岛素治疗的2型糖尿病患者血浆内脏脂肪素（Visfatin）水平的变化与胰岛素抵抗及血糖的关系。方法共32例2型糖尿病患者,比较其治疗前后空腹（FPG）及餐后血糖（2hPG）、甘油三酯（TG）、糖化血红蛋白（HbA1c）、空腹胰岛素（Fins）、胰岛素抵抗指数（HOMA-IR）、胰岛素分泌指数（HOMA-β）、Visfatin等相关指标。同时选择性别、年龄等相匹配的26名健康体检者作为对照组进行比较。结果32例糖尿病患者治疗前后的TG、FPG、2hPG、HbA]C、HOMA-IR、HOMA-13差异有统计学意义（P〈0．05）,治疗后Visfatin水平降低（P〈0．05）,与健康人相比,糖尿病患者Visfatin水平降低（Pd0．01）;Pearson相关分析显示Visfatin与HbA1C、Fins、HOMA-IR呈正相关（r=0．259,Pd0．05;r=0．586,P〈0．01;r=0．385,P〈0．01）。多元线性逐步回归分析表明HOMA-IR是血浆Vis—fatin的独立相关因素。结论2型糖尿病患者血浆Visfatin水平的变化与胰岛素抵抗及平均血糖有关,可能在糖尿病及胰岛素抵抗的发病机制中具有一定的作用。     

初发2型糖尿病患者血脂联素和瘦素与胰岛素抵抗的关系

目的 研究初发2型糖尿病患者血脂联素和瘦素水平的变化及其与胰岛素抵抗的关系.方法 选择46例初发2型糖尿病患者,及与其体脂含量相匹配的糖耐量正常者43名,计算体重指数(BMI)和腰臀围比(WHR),并空腹采血,测定血糖(FPG)、血脂、真胰岛素(FTI)、胰岛素原(FPI)、脂联素和瘦素浓度,分析血清脂联素和瘦素水平的变化及其与胰岛素抵抗的关系.用胰岛素抵抗指数(HOMA-IR)评估胰岛素抵抗程度.结果 2型糖尿病组与正常对照组比较,年龄、BMI无统计学意义(P>0.05),三酰甘油、FPG及FPI和HOMA-IR明显升高(P<0.05或P<0.01),舒张压、脂联素水平明显降低(P<0.05或P<0.01);相关分析显示,脂联素与FPG、FTI、HOMA-IR、BMI、WHR呈负相关(P<0.05或P<0.01);瘦素与BMI、FTI、HOMA-IR、FPG呈正相关(P<0.05或P<0.01),与WHR无关.人血清脂联素和瘦素间无相关性.结论 人血清脂联素和瘦素与胰岛素抵抗密切相关,体脂含量相同的初发2型糖尿病患者血脂联素水平低于正常人.     

2型糖尿病患者血清鸢尾素水平与胰岛素抵抗的相关性

目的 探讨血清鸢尾素（irisin）水平与胰岛素抵抗是否存在相关性.方法 选取2013年6月至2014年1月在浙江大学医学院附属第一医院内分泌科2型糖尿病（T2DM）住院患者82例（男48例,女34例）为T2DM组,同期体检中心健康体检者62名（男33名,女29名）为对照组（NC组）.所有受试者均接受体格检查、生化指标和血清irisin水平检测,T2DM组加测空腹胰岛素（FINS）、餐后血糖.采用Studentt检验、Pearson相关分析和多元线性回归进行统计学分析.结果 T2DM组血清irisin浓度明显低于NC组[（1.5±0.6）比（2.6±0.6）ng/L,t=-10.233,P＜0.05];且经Pearson相关分析,T2DM组血清irisin浓度与腰臀比（WHR）、餐后2h血糖、稳态模型胰岛素抵抗指数（HOMA-IR）呈负相关（r=-0.603、-0.295、-0.22,均P＜0.05）;与病程、性别、年龄、是否吸烟、是否存在并发症、是否存在合并症、体质指数（BMI）、收缩压、舒张压、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、FINS、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、甘油三酯（TG）、动脉粥样硬化指数（AI）无明显相关性（均P＞0.05）;进一步用多元线性回归分析发现,在排除性别、年龄、血压、并发症、合并症后,血清irisin水平与WHR呈显著负相关,WHR是血清irisin水平独立的负性影响因子（标准化回归系数=-3.995,P＜0.05）.结论 T2DM患者血清irisin水平较正常人减低,并与胰岛素抵抗的发生发展有关.     

2型糖尿病患者瘦素、生长激素释放肽与胰岛素抵抗的相关性研究

目的 探讨2型糖尿病患者血清瘦素（Leptin）和生长激素释放肽（Ghrelin）与胰岛素抵抗的相关性.方法 随机选定62例2型糖尿病患者和48例正常对照人群,并根据BMI将糖尿病人群分为肥胖糖尿病组和非肥胖糖尿病组,均测定身高、体重、空腹血糖（FPG）、空腹胰岛素（FINS）、Leptin、Ghrelin和血脂,计算胰岛素抵抗指数（HOMA-IR）,分析Leptin、Ghrelin与HOMA-IR的相关性.结果 与对照组比较,糖尿病组Ghrelin水平明显下降（P＜0.001）,而Leptin水平无显著性差异（P＞0.05）;与非肥胖糖尿病组比较,肥胖糖尿病组Leptin水平明显增高（P＜0.001）,而Ghrelin无显著性差异（P＞0.05）.糖尿病患者中HOMA-IR与Ghrelin呈负相关（r=-0.372,P=0.043）;与Leptin呈正相关（r=0.389,P=0.034）,Ghrelin与Leptin呈负相关（r=-0.362,P=0.049）.结论 2型糖尿病患者血清Leptin和Ghrelin与胰岛素抵抗密切相关.     

Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity

Objective

The aim of this study was to evaluate the association of serum visfatin, adiponectin and leptin with 2 diabetes mellitus (T2DM) in the context of the role of obesity or insulin resistance, which is not well understood.

Methods

A total of 76 newly-diagnosed T2DM patients and 76 healthy control subjects, matched for age, body mass index (BMI) and sex ratio, were enrolled. Anthropometric parameters, glycemic and lipid profile, insulin resistance (measured by homeostasis model assessment of insulin resistance index [HOMA-IR]), leptin, adiponectin, and visfatin were assessed.

Results

On the contrary to adiponectin, serum leptin and visfatin levels were higher in T2DM patients compared with controls (10.07 ± 4.5, 15.87 ± 16.4, and 5.49 ± 2.4 vs. 12.22 ± 4.9 μg/ml, 8.5 ± 7.8 ng/ml and 3.58 ± 2.2 ng/ml, respectively, P < 0.01). Waist circumference and BMI were correlated with leptin and adiponectin but not with visfatin. Leptin, adiponectin and visfatin all were associated with T2DM following adjusting for obesity measures. After controlling for HOMA-IR, visfatin remained as an independent predictor of T2DM (odds ratio = 1.32, P < 0.05). In a multiple regression analysis to determine visfatin only triglycerides and fasting glucose remained in the model (P < 0.05).

Conclusion

Elevation of visfatin in T2DM is independent of obesity and insulin resistance and is mainly determined by fasting glucose and triglycerides.     

2型糖尿病Leptin与胰岛素抵抗的关系

目的　研究新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗的相关关系。方法　以空腹血浆胰岛素与血糖乘积的倒数作为胰岛素抵抗程度的指标 ,采用酶联免疫法测定 31名正常人、2 9例新诊断非肥胖 2型糖尿病患者的血清leptin水平。 结果　新诊断非肥胖 2型糖尿病患者 ,血清leptin浓度与胰岛素敏感性指数有显著负相关 (r =-0 .37,P <0 .0 5 ) ,主要表现在男性 (r =-0 .6 6 ,P <0 .0 1)。leptin与空腹血胰岛素 (r =-0 .45 ,P <0 .0 5 )、空腹血糖(r =-0 .37,P <0 .0 5 )有正相关关系。男性患者leptin血清水平比正常男性有显著性升高 (P<0 .0 5 )。结论　新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗程度有显著正相关关系 ,leptin与 2型糖尿病的发病有关     

The microvasculature in insulin resistance and type 2 diabetes

Insulin resistance of muscle has been attributed to impairment of elements of insulin signaling, glucose transport, and/or metabolism within the muscle cells. This article explores the notion that a component of insulin resistance in vivo may result from impaired hemodynamic effects of this hormone to facilitate access to the muscle cells for itself and other nutrients, including glucose. In chronic situations this may manifest as a decreased capillary density of muscle, but in the acute, there may be impaired mechanisms for increasing total limb blood flow or for achieving optimal microvascular perfusion. Newly developed techniques show that insulin acts to recruit muscle capillary flow to enhance microvascular perfusion in animals and humans. This microvascular effect of insulin correlates closely with muscle glucose uptake, is independent of increases in bulk blood flow, and is impaired in obese insulin-resistant patients. Similarly, there are impaired vasodilatory responses in the skin of diabetic subjects.     

Levels of leptin in plasma of patients with type 2 diabetes

Leptin, the product of ob gene is secreted by adipose tissue. It is believed that leptin plays an important role in energy balance. The secretion of leptin by adipose tissue is influenced by insulin. The aim of the present study was the estimation of plasma leptin concentrations in patients with type 2 diabetes mellitus. The study was carried out in 21 diabetic obese patients (BMI > 27.5), 8 diabetic patients with BMI < 27.5, 24 obese patients with normal glucose tolerance (BMI > 27.5) and 10 patients from the control group (BMI < 27.5). The mean leptin concentration in obese diabetic patients was 22.5 + 6.5 ng/ml and was not significantly different from that in obese patients without diabetes (24.1 + 10.3 ng/ml) but differed markedly in comparison to the normal weight diabetic patients (7.9 + 4.3 ng/ml, p < 0.01). Plasma leptin concentration correlated significantly and positively with BMI and fasting insulin in all studied groups. There was no significant correlation between leptin and glycated hemoglobin, total cholesterol and triglycerides. We conclude that serum leptin concentrations in patients with type 2 diabetes depends mainly on the amount of body fat.     

2型糖尿病患者血清瘦素与皮质醇和胰岛素抵抗的关系及罗格列酮干预作用

目的探讨T2DM患者血清瘦素、皮质醇水平与胰岛素抵抗（IR）的关系,观察罗格列酮（RGZ）干预作用。方法以HOMA-IR作为评估IR程度的指标,分别测定30例T2DM患者（DM组）和30例对照者（NC组）的FPG、Fins、瘦素、皮质醇。DM组服用RGZ4mg／d,12周后复查。结果DM组血清瘦素、糖皮质激素水平高于NC组。RGZ治疗后血糖、瘦素、皮质醇水平下降,IR改善。结论T2DM患者血清瘦素、皮质激素水平和IR呈正相关。罗格列酮治疗可降低血糖、瘦素及皮质醇水平,改善IR。     

2型糖尿病患者血浆基质金属蛋白酶1与胰岛素抵抗的相关性

基质金属蛋白酶 (ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅｓ,ＭＭＰｓ)是一组参与细胞外基质 (ＥＣＭ)降解的内肽酶超家族 ,其中ＭＭＰ 1为人类间质胶原酶 ,它最重要的底物是Ⅲ型胶原。在糖尿病肾病 (ＤＮ)的ＥＣＭ中 ,原来无表达的Ⅲ型胶原沉积于系膜区 ,为肾小球硬化的标志〔1〕。本研究旨在探讨胰岛素抵抗 (ｉｎｓｕｌｉｎｒｅｓｉｓｔａｎｃｅ,ＩＲ)对ＭＭＰ 1表达调节的影响〔1〕。一、对象和方法1.受试对象及分组 :2型糖尿病组为符合 1999年ＷＨＯ诊断标准确诊的 2型糖尿病患者 6 0例 (男 2 9,女 31) ,年龄(5 9.5± 11.4 )岁…     

Myokines in insulin resistance and type 2 diabetes

Skeletal muscle represents the largest organ of the body in non-obese individuals and is now considered to be an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the health-promoting effects of regular physical activity. Although hundreds of myokines have recently been described in proteomic studies, we currently have a rather limited knowledge of the specific role these myokines play in the prevention of insulin resistance, inflammation and associated metabolic dysfunction. Several myokines are known to have both local and endocrine functions, but in many cases the contribution of physical activity to the systemic level of these molecules remains as yet unexplored. Very recently, novel myokines such as irisin, which is thought to induce a white to brown shift in adipocytes, have gained considerable interest as potential therapeutic targets. In this review, we summarise the most recent findings on the role of myokines in the regulation of substrate metabolism and insulin sensitivity. We further explore the role of myokines in the regulation of inflammation and provide a critical assessment of irisin and other myokines regarding their potential as therapeutic targets.