2型糖尿病病人的内脏脂肪性肥胖和胰岛素抵抗

目的 探讨2型糖尿病病人内脏型肥胖和胰岛素抵抗的关系。方法 对50例2型糖尿病病人进行内脏脂肪测定,采用CT影像学检查方法;胰岛素抵抗采用高胰岛素—正血糖钳夹试验,得出葡萄糖利用率。根据有无内脏型肥胖将病人分为内脏肥胖组和非内脏肥胖组。结果 (1)内脏肥胖组的内脏脂肪平均值为127.28cm~2,非内脏肥胖组为70.41cm~2;内脏肥胖组比非肥胖型组有更高的甘油三酯水平和收缩压;内脏肥胖组的葡萄糖利用率平均值为3.54mg/(kg·min),非内脏肥胖组的平均值为9.66mg/(kg·min),二组差异有显著意义。(2)内脏脂肪和皮下脂肪与2型糖尿病病人胰岛素介导的葡萄糖利用率显著相关,内脏脂肪是胰岛素抵抗的影响的最强指数,即使与年龄、性别及体重指数校正以后也不影响结果。结论 内脏脂肪肥胖和心血管危险因子密切相关,是2型糖尿病胰岛素抵抗的独立影响因子。     

2型糖尿病患者血清GH、IGF-I浓度改变及相关因素的研究

目的通过放免测定方法了解2型DM患者GH／IGF-I轴的改变与1型DM患者有何不同。方法对19例1型DM和98例2型DM患者的血清基础GH及IGF-I浓度进行测定。将2型DM患者血清IGF-I浓度与其各项临床及生化指标进行多元相关回归分析。结果1型DM患者GH水平(2.53士0.51μg/L)明显高于对照组(1.36士0.27μg／L,P＜0.05);IGF-I水平(191.5±14.1μg/L)则显著低于对照组(266.3士17.7μg/L,P＜0.01)。2型DM患者GH(0.60±0.11μg/L)水平与对照组(0.74士0.07μg/L)无显著性差异(P＞0.05),IGF-I(126.1士3.2μg/L)水平较正常(153.4士8.3μg/L)明显降低(P＜0.05)。2型DM患者血清IGF-I浓度与年龄(P＜0.05)及HbA1c(P＜0.05)呈负相关,与平均动脉压(P＜0.05)和空腹胰岛素(P＜0.01)呈正相关。结论2型DM患者血清基础GH和IGF-I改变与1型DM患者有所不同,这种异常改变可能与持续高血糖水平有关。     

2型糖尿病病人高血压与胰岛素抵抗的关系

目的：探讨高血压与胰岛素抵抗之间的关系。方法：2型糖尿病高血压组123例,正常血压组120例,测定FPG,FINS,RC,TG,UA,MAU,血压,计算BMI,评价胰岛素抵抗和β细胞功能采用稳态模式评估法及改良胰岛素敏感性指数公式计算,结果：高血压组ISI显著低于正常血压组,HOMA－β cell,HOMA－IR显著高于正常血压组（P＜0．005）,正常体重者也有相同的结果（P＜0．05）,两组ISI与FPG,FINS,BIM均呈显著负相关（P＜0．05）,高血压组ISI与TC,TG,UA呈弱负相关（P＜0．5）,结论：2型糖尿病伴高血压病人无论是否肥胖都存在胰岛素抵抗,肥胖病人胰岛素抵抗理炙严重。     

MCP-1与胰岛素抵抗和2型糖尿病的关系

近年来炎症学说在胰岛素抵抗及2型糖尿病发病机制中的作用备受关注。越来越多的研究提示,胰岛素抵抗和2型糖尿病是一个慢性非特异性炎症过程。单核细胞趋化蛋白-1作为炎症趋化因子CC亚族的一员,在趋化单核细胞和T淋巴细胞,诱导单核细胞、内皮细胞表达黏附分子,使各种炎性细胞尤其是单核/巨噬细胞向病变部位聚集的过程中发挥了决定性作用。而这种免疫和炎症过程有可能导致胰岛素抵抗和2型糖尿病的发生和发展。     

Ghrelin与能量平衡及糖代谢的关系

Ghrelin是生长激素促分泌物受体的第一个内源性配体,具有促进生长激素分泌、促进摄食、减少脂肪利用等作用,并与胰岛素、瘦素等相互作用,影响能量平衡及糖代谢,因而与肥胖、胰岛素抵抗及2型糖尿病密切相关。进一步研究ghrelin的作用对研究肥胖、胰岛素抵抗、2型糖尿病的发生、发展过程具有指导意义。     

血清抵抗素水平与肥胖及2型糖尿病的关系

目的　研究血清抵抗素水平与肥胖、2型糖尿病 (T2DM )和胰岛素抵抗 (IR)的关系。　方法　用酶免疫测定法检测 31例单纯肥胖、2 7例T2DM及 30名正常人空腹血清抵抗素水平。　结果　单纯肥胖组、T2DM组及正常对照组空腹抵抗素分别为 ( 4 1± 13)、( 4 3± 11)和 ( 5 3± 7) μg/L。单纯肥胖组和T2DM组血清抵抗素浓度均低于正常对照组 (P <0 0 1)。空腹血清抵抗素与体质指数(BMI)、胰岛素抵抗指数 (HOMA IR)分别呈负相关 (r =- 0 2 92及 - 0 319,P <0 0 1) ,与空腹胰岛素、腰围和体脂百分比 (BF % )也呈负相关 (r =- 0 2 5 9,- 0 2 31及 - 0 2 39,P <0 0 5 )。多元逐步回归分析显示 ,HOMA IR为影响抵抗素最为显著的因素 (R2 =0 0 86 )。　结论　肥胖及T2DM患者血清抵抗素水平偏低。血清抵抗素与BMI、体脂百分比、腰围、空腹胰岛素和HOMA IR呈负相关。抵抗素可能在人类IR的发病中起一定的作用     

2型糖尿病患者体脂分布与胰岛素抵抗的关系

目的 了解2型糖尿病患者体脂分布与胰岛素抵抗(IR)的关系,比较各种体脂评价方法。方法 41例2型糖尿病患者,以双能X线吸收法(DEXA)测定全身脂肪百分比(BF％)及局部脂肪百分比,同时测定身高、体重,计算体重指数(BMI),测定腰围、臀围,并计算其比值(WHR),以生物电阻抗法体脂测定仪(TANITA仪)测定BF％,以空腹血糖与胰岛素乘积的倒数(取自然对数LnIAI)作为IR指标,分析体脂分布与IR的关系。评价TANITA仪测定的BF％与DEXA测定结果的相关性。结果 2型糖尿病患者腹型肥胖组LnIAI(-4.6±0.6)明显低于非腹型肥胖组(-4.2±0.7),腹型肥胖组中BMI与LnIAI相关(r=-0.488,P=0.021),而非腹型肥胖组中各指标与LnIAI均不相关。各种体脂指标经聚类分析后BMI与腰围、WHR归为一类。TANITA与DEXA测定的BF％显著相关(r=0.839)。结论 2型糖尿病患者存在腹型肥胖,则胰岛素抵抗明显。在2型糖尿病患者中,BMI仍是反映胰岛素抵抗的较佳指标。TANITA仪与DEXA测定的BF％显著相关。     

Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance

We report a 38-year-old female with severe insulin resistance who developed type 1 diabetes after being diagnosed with type 2 diabetes. At the initial examination, BMI was 31.8 kg/m² and HbA1c 10.8%. Her insulin secretion was sufficient (urinary CPR 80 μg/day) and the GAD antibody was negative. Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody positive, and insulin secretion decreased (urinary CPR 18 μg/day). Further, a hyperinsulinemic–euglycemic cramp study using an artificial pancreas showed that the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg); normal, 7.4 ± 2.4 (mean ± S.D.)]. An HLA-analysis showed that she was a homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy, glucose control was not improved. Pioglitazone could not be used because of side effects, however, metformin was effective for glucose control. The accumulation of case reports of patients with type 1 diabetes and insulin resistance is important for studying the relationship between the onset of the disease and insulin resistance, and for developing an effective treatment strategy.     

Foxa2与2型糖尿病肝脏胰岛素抵抗的分子病因学——解读2006年美国糖尿病学会(ADA)"杰出科学成就奖"演讲报告

2006年美国糖尿病学会(ADA)年会上,Markus Stoffel教授获得杰出科学成就奖。会上Stoffel教授作了题为“从饥饿中了解到的:2型糖尿病肝脏胰岛素抵抗的分子病因学”的演讲。本文对其工作作一综述。包括:胰岛素通过Foxa2调节β氧化和酮体形成;Foxa2在胰岛素抵抗及糖尿病中的作用;Foxa2调节极低密度脂蛋白的生成和分泌;Foxa2调节载脂蛋白M、血浆前β脂蛋白和高密度脂蛋白水平。     

2型糖尿病与恶性肿瘤

2型糖尿病不仅是一个严重的健康问题，还与恶性肿瘤有着密切的联系。近年来流行病学研究证实2型糖尿病与一些常见恶性肿瘤如结、直肠癌、肝癌、胰腺癌、乳腺癌以及子宫内膜癌的发病有关，但其关联的确切机理仍无定论，可能与高血糖、胰岛素及胰岛素样生长因子、内皮素、脂联素、微量元素、激素和药物等诸多因素有关。     

Inflammation as a link between obesity,metabolic syndrome and type 2 diabetes

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammatory therapies could have a place in prevention and treatment of type 2 diabetes.     

2型糖尿病纤溶系统变化与胰岛素抵抗的关系

目的探讨2型糖尿病患者纤溶活性变化与胰岛素抵抗之间的关系。方法采用酶联免疫吸附法测定63例2型糖尿病患者（包括无血管并发症组30例和有血管并发症组33例）和25例正常对照者血浆组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）含量,结合临床资料分析其变化趋势及影响因素。结果2型糖尿病患者血浆t-PA含量明显降低（P〈0．01）,而PAI-1含量明显升高（P〈0．01）,合并血管病变者,此变化更为显著（均P〈0．001）。多元逐步回归分析显示,HOMA模型胰岛素抵抗指数（HOMA—IR）是PAI-1升高的独立危险因素。结论2型糖尿病患者纤溶活性降低,胰岛素抵抗在降低其纤溶活性,并发血管病变中起了重要作用。     

2型糖尿病合并高血压与胰岛素生长因子-1的相关性研究

目的探讨2型糖尿病合并高血压与胰岛素生长因子-1(IGF-I)之间的关系。方法共收集了53例2型糖尿病合并高血压患者静脉血检测基本数值并用放免法测IGF-I值,与高血压、2型糖尿病患者和正常人对照。观察2型糖尿病合并高血压组血压分级IGF-I的变化。结果2型糖尿病合并高血压组IGF-I与年龄呈负相关(r=-0.387,P<0.01),与甘油三酯、载脂蛋白A、尿酸和收缩压呈正相关(P<0.05);血压分级后IGF-I水平间无明显差别(P>0.05),IGF-I值在血压分级后与糖尿病并发症的构成无关联性(χ2=4.605,P>0.05)。结论2型糖尿病合并高血压时血压分级后IGF-I水平无明显变化,与存在的糖尿病并发症无明显关联性,而与高血压危险因素有关。     

肥胖和非肥胖的2型糖尿病患者胰岛素敏感性和β细胞功能研究

目的 探讨在2型糖尿病患者中肥胖对胰岛素抵抗程度和胰岛β细胞分泌功能的影响。 方法 运用减少样本数的Bergman微小模型技术结合多样本静脉葡萄糖耐量试验检测正常个体(15名)、肥胖和非肥胖2型糖尿病患者(分别为20和14例)的胰岛素敏感指数(S_I)、机体对葡萄糖的急性胰岛素反应(AIRg)和处理指数(DI=S_I×AIRg),同时测定其它临床指标,包括体重指数、腰臀比等。结果 与正常对照组相比,2型糖尿病患者的S_I、AIRg和DI都明显降低(P<0.01)。肥胖组的S_I较非肥胖组低(P<0.05),而其AIRg和DI水平较高(P<0.05),差异显著。结论 肥胖2型糖尿病患者比非肥胖患者存在更为严重的胰岛素抵抗,但机体早期胰岛β细胞胰岛素分泌功能相对能部分代偿。     

2型糖尿病血清瘦素质量浓度与胰岛素抵抗的关系

目的探讨2型糖尿病人群血清瘦素水平与胰岛素抵抗的关系。方法2001-102002-08对河北医科大学第三医院的196例受试者(2型糖尿病者118例、对照者78名)用放射免疫法测定空腹血清瘦素水平,同时测量身高、体重、腰围、臀围。结果糖化血红蛋白(HbA1c)、收缩压(SBP)、甘油三酯(TG)和瘦素(Leptin)是影响胰岛素敏感性的因素;2型糖尿病组瘦素质量浓度高于对照组;肥胖者瘦素质量浓度显著升高,而2型糖尿病组内肥胖与非肥胖者之间瘦素质量浓度差异无显著性。结论肥胖者大多存在胰岛素抵抗;2型糖尿病人无论肥胖与否均存在一定程度的胰岛素抵抗。     

2型糖尿病伴高甘油三酯血症患者血清胰岛素样生长因子结合蛋白1水平与胰岛素抵抗的相关性分析

目的探讨糖、脂代谢不同人群的血清胰岛素样生长因子结合蛋白1（IGFBP-1）水平与胰岛素抵抗（IR）的关系。方法选取正常人（NC）、高TG血症患者、2型糖尿病（T2DM）患者及T2DM＋高TG患者共66例,测定血清IGFBP-1、胰岛素、血糖和血脂水平。结果（1）血清IGFBP-1水平,高TG血症组较NC组、T2DM＋高TG组较T2DM组均明显下降（P〈0.05）。（2）多元逐步回归分析显示血清IGFBP-1水平与TG、HOMA-IR负相关（P〈0.05）,与HDL-C正相关（P〈0.05）。结论高TG血症人群血清IGFBP-1明显下降,提示存在明显肝脏IR。     

2型糖尿病患者血清胰岛素样生长因子Ⅰ及其结合蛋白与大血管并发症的关系

2型糖尿病(T2DM)合并大血管病变者血清游离胰岛素样生长因子Ⅰ(IGF-I)水平较无大血管病变组降低(P<0·01),胰岛素样生长因子结合蛋白1浓度与WHR、胰岛素抵抗指数呈负相关。表明低IGF-I可能参与糖尿病大血管并发症的发生。胰岛素样生长因子结合蛋白1的浓度反映了胰岛素抵抗状态。     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress

Aim

This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.

Methods

Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.

Results

Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.

Conclusions

Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects

Aims/hypothesis Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor α subunit. This inhibition is enhanced by the minor Q allele of the K121Q polymorphism (rs1044498) in the gene (ENPP1) encoding PC-1. This polymorphism has been studied in relation to insulin resistance, type 2 diabetes and obesity in several populations with conflicting results. We assessed the impact of the ENPP1 K121Q polymorphism on type 2 diabetes, obesity and quantitative metabolic traits in 7,333 Danes.Subjects and methods The K121Q polymorphism was genotyped in the population-based Inter99 study cohort (5,961 subjects) and in a group of 1,386 patients with type 2 diabetes. All subjects were Danish whites.Results No significant associations with type 2 diabetes or related quantitative metabolic traits, including measures of insulin resistance, were detected. However, a meta-analysis of the present and published studies revealed an association with type 2 diabetes (odds ratio per Q allele, 1.17 [95% CI 1.10–1.25], p=1×10⁻⁶). In case–control studies comparing subjects of different BMI strata, we observed a putative association of the codon 121 QQ genotype with being overweight (BMI>25 kg/m²; odds ratio 1.63 [95% CI 1.09–2.46], p=0.015), an association not observed when comparing other levels of BMI or when analysing BMI as a quantitative trait.Conclusions/interpretation In a meta-analysis, the ENPP1 codon 121 Q allele associates with type 2 diabetes. However, a similar association was not found in the present study of Danish white subjects. The effect of this variant on obesity in Danish subjects is contentious and further study is needed.     

非特异性免疫与胰岛素抵抗及2型糖尿病

越来越多的研究表明,非特异性免疫系统激活参与胰岛素抵抗和2型糖尿病的发生、发展.糖尿病患者存在细胞因子介导的慢性低度炎性反应状态,伴随着非特异性免疫系统的上调.非特异性免疫参与胰岛素抵抗和2型糖尿病发病的作用途径包括:遗传变异、巨噬细胞的促炎作用、慢性感染、Toll样受体(TLR)途径、巨噬细胞迁移抑制因子(MIF)水平增高等.通过锻炼或药物干预非特异性免疫系统有可能改善胰岛素抵抗及2型糖尿病.