瘦素、抵抗素与胰岛素抵抗

第五届岭南心血管病学术研讨会暨近年来心血管病防治的前沿问题及新观点学习班于 2 0 0 3年 4月3～ 7日在广州市广东大厦举行 ,来自广东、广西、湖南、海南及其他中南各省、市自治区从事心血管疾病专业人员共 10 0 0余人参加 ,会议期间邀请了国内著名的心脏病专家进行专题讲座 ,深得听众好评 ,本刊特将专家讲稿汇集刊登 ,以满足广大读者的要求。《岭南心血管病杂志》编辑部     

血清抵抗素水平与肥胖及胰岛素抵抗相关性的研究

目的　探讨 2型糖尿病 (T2DM)患者血清抵抗素水平与肥胖及胰岛素抵抗 (IR)的关系。方法　酶联免疫法测定T2DM患者 86例及对照组 42例的空腹血清抵抗素水平。记录受试对象性别、年龄、病程、身高、体重、腰围 (W )、臀围 (H)、血压 ,并检测空腹血脂、血糖 (Glu)、肾功能、胰岛素 (INS)、雌二醇 (E2 )、睾酮 (T)等生化指标。结果　无论是T2DM组还是对照组 ,肥胖者血清抵抗素水平与非肥胖者比较 ,均具有统计学差异(P <0 0 1 ) ,T2DM组与对照组比较其血清抵抗素水平无显著性差异 ;采用相关分析发现 ,血清抵抗素浓度与BMI、腰围、WHR、BF %、TG、ApoB、FINS、SBP、DBP呈显著正相关 ,与ISI显著负相关 ,男性抵抗素水平与T呈正相关 ;采用多元逐步回归分发现BF %、FINS、ISI、腰围为影响抵抗素最显著的因素 (R2 =0 78)。结论　T2DM组与对照组比较其血清抵抗素水平无显著性差异 ,而无论是T2DM组还是对照组 ,肥胖者血清抵抗素水平与非肥胖者比较 ,差别均具有统计学意义 (P <0 0 0 1 )。血清高抵抗素水平与BF %、FINS、ISI、腰围的相关性提示 ,抵抗素可能在肥胖、IR及T2DM的发病中起一定作用     

T2DM患者血浆内脏脂肪素、瘦素与胰岛素抵抗的相关性研究

目的 探讨2型糖尿病(T2DM)患者血浆内脏脂肪素、瘦素水平与胰岛素抵抗(IR)的相关性.方法 102例T2DM患者和64例正常糖耐量(NGT)对照者,根据BMl分为肥胖组(Ob)和非肥胖(Non-Ob)组,均测定空腹血浆内脏脂肪素、瘦素和相关临床指标,计算胰岛素抵抗指数(HOMA-IR)和腰臀比(WHR).结果 T2DM组与NGT组比较空腹血浆内脏脂肪素和瘦素水平明显升高(t=3.922,P=0.00;t=2.128,P=0.038).相关分析显示T2DM患者空腹血浆内脏脂肪紊与HOMA-IR、WHR、瘦素、HbA<,1> c和TG正相关(r=0.543,P=0.001;r=0.442,P=0.008;r=0.385,P=0.013,r=0.345,P=0.025;r=0.427,P=0.005),瘦素与HOMA-IR、性别、BMI正相关(r=0.578,P<0.01;r=0.547,P<0.01;r=0.607,P<0.01).结论 T2DM患者空腹血浆内脏脂肪素和瘦素水平显著升高,且与IR关系密切.     

抵抗素与胰岛素抵抗及2型糖尿病微血管病变的关系

目的 探讨血浆抵抗素与胰岛素抵抗及2型糖尿病微血管病变之间的相互关系.方法 随机抽选60例临床确诊的2型糖尿病患者,按有无微血管并发症分为2组:微血管并发症组30例和无微血管并发症组30例,以24例同期体检的健康志愿者作为对照组.采用双抗体夹心酶联免疫吸附试验测定所选84例实验对象的血浆抵抗素浓度,放射免疫分析法测定胰岛素,氧化酶法测定血糖,全自动生化分析仪检测血脂.结果 (1)微血管并发症组组血浆抵抗素浓度高于无微血管并发症组及对照组(P<0.05)差异有统计学意义;(2)60例病例的Pearson相关分析得出:血浆抵抗素浓度与FINS、HbAlc、HOMA-IR、TC、LDL-C正相关,与FPG、TG、BMI、HDL-C均无相关性.结论 空腹血浆抵抗素水平在2型糖尿病有微血管病变者中显著升高,并与2型糖尿病患者血糖控制不良的程度有关、与2型糖尿病脂代谢紊乱相关,在2型糖尿病微血管病的发生、发展中可能起一定作用.     

2型糖尿病患者血清瘦素水平与胰岛素抵抗的相关性研究

2003年9月至2004年11月,我们对57例2型糖尿病患者行血清瘦素(LEP)水平检测及胰岛素(INS)释放试验,旨在探讨LEP与INS抵抗的关系。     

2型糖尿病胰岛素抵抗与瘦素及糖尿病肾病的关系

为探讨 2型糖尿病患者胰岛素抵抗与瘦素和糖尿病肾病(DN)的关系 ,我们对 2 0 0 1年 7月以来在本院门诊治疗和住院的 112例 2型糖尿病患者观察了胰岛素敏感指数 (IAI)、瘦素 (L PT)和尿白蛋白排泄率 (UAER)。现报告如下。临床资料 :112例 2型糖尿病患者均按 WHO标准确诊 ,男 6 0例 ,女 5 2例 ;年龄 4 0～ 6 5岁 ;病程 1～ 6年。根据本院正常值将 112例 2型糖尿病患者分为 :1A组 :即 IAI异常组、胰岛素抵抗 (IR)组。男 30例 ,女 2 8例 ;年龄 4 0～ 6 5岁。 2 B组 :即 IAI正常组、非胰岛素抵抗 (NIR)组。男 30例 ,女 2 4例 ;年龄 4…     

2型糖尿病患者血清瘦素水平与胰岛素抵抗关系的研究

胰岛素抵抗是 2型糖尿病的发病机制之一 ,本研究通过对2型糖尿病患者血清瘦素、空腹胰岛素等指标的测定 ,旨在研究2型糖尿病患者血清瘦素水平与胰岛素抵抗之间的关系及影响血清瘦素水平的因素。一、对象和方法1.按 1997年 ADA/ WHO糖尿病诊断标准 ,收集 2型糖尿病患者 (糖尿病组 ) 10 1例 ,男 5 1例、女 5 0例 (排除胰岛素治疗者 )。正常对照 6 8例 ,男 36例、女 32例。2 .受试对象测量身高、体重并采空腹静脉血 ,常规方法测定空腹血糖 (FPG) ,糖化血红蛋白 (Hb A1c) ,血肌酐 (Cr) ,总胆固醇 (TC) ,甘油三酯 (TG)及高密度脂蛋白胆固…     

高脂大鼠抵抗素基因的上调表达及与胰岛素、瘦素的相关性

目的 观察SD大鼠高脂饮食状态下脂肪组织中抵抗素的表达及其与胰岛素抵抗以及糖尿病、瘦素等的关系。方法 采用RT—PCR、割胶纯化、基因构建测序的方法，证实为目的片段后，对高脂饮食SD大鼠的脂肪组织进行mRNA抽提，再以此为模板进行半定量RT—PCR扩增及Northern印迹分析。同时检测血清中胰岛素、瘦素水平，并行糖耐量试验、胰岛素释放试验等。结果 (1)成功构建了抵抗素的基因，并经测序证实。(2)与对照组相比，高脂饮食组大鼠脂肪组织中抵抗素表达明显升高，血糖水平、胰岛素水平以及瘦素水平升高。(3)高脂饮食组大鼠在4个月时下丘脑中瘦素受体表达较对照组明显降低。结论 抵抗素表达量的变化与饮食有关，抵抗素可能是胰岛素抵抗、糖尿病发病的一个前期信号，其作用可能与瘦素、瘦素受体有一定关系。     

小檗碱对脂肪细胞瘦素和抵抗素基因表达的影响

小檗碱是中药黄连的主要成分，具有改善胰岛素抵抗、降血糖和纠正脂质代谢紊乱的作用，临床上用于治疗2型糖尿病”。近年来．脂肪组织在2型糖屎病发病中的作用日益受到重视．脂肪细胞分秘的多种激素在机体的糖、脂代谢中起重要作用，其中瘦素(1eplin)和抵抗素(resistuin)的作用备受关注。本实验采用的313-L1细胞株是一种来自小鼠的前     

西布曲明对2型糖尿病患者瘦素及胰岛素抵抗的影响

肥胖导致的胰岛素抵抗(IR)是糖尿病、高血压、代谢紊乱发生的基础．并与糖尿病慢性并发症的发生发展密切相关。2001年1月至2002年1月，我们应用西布曲明治疗2型糖尿病患者30例，观察治疗前后患者血脂、基础胰岛素、胰岛素抵抗指数、血清空腹瘦素水平的变化．以评价西布曲明在2型糖尿病治疗中的应用价值。     

Insulin resistance and metabolic syndrome in type 1 diabetes mellitus

Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40% in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.     

2型糖尿病和非酒精性脂肪肝与脂肪细胞因子的相关性

目的研究2型糖尿病和非酒精性脂肪肝（NAFLD）与脂肪细胞因子的相关性。方法240例受试者分为正常对照组47例（A组）、非酒精性脂肪肝组53例（B组）、2型糖尿病组79例（C组）、2型糖尿病伴非酒精性脂肪肝组61例（D组）,进行肝功、血脂、血糖、胰岛素水平、血尿酸、脂联素（APN）、肿瘤坏死因子（TNF-d）的测定以及腹部B超检查。结果B组体质量、体质量指数、腰围、血脂、胰岛素水平、胰岛素抵抗指数（HOMA．IR）、肝酶、血尿酸显著高于A组（P〈0．01）;B细胞功能评估显著低于A组（P〈0．01）;其空腹胰岛素水平、胆固醇、甘油三酯、血尿酸水平、丙氨酸转氨酶（ALT）、y-谷氨酰转移酶（GGT）高于C组（P〈0．01）。D组体质量、腰围、空腹胰岛素水平、甘油三酯、HOMA．IR、ALT、GGT显著高于C组（P〈0．01）,其血压、HOMA．IR显著高于B组（P〈0．01）。B组,C组,D组与A组相比APN明显下降（P〈0．01）,TNF-a明显升高（P〈0．01）,D组与B组,C组相比ANP下降（P〈0．01）,TNF-a上升（P〈0．01）。Logistic回归分析发现,甘油三酯、TNF．d为NAFLD的独立危险因素。Spearman相关分析显示,ANP与HOMA．IR、甘油三酯、腰围、TNF-a呈负相关,TNF-a与空腹胰岛素及HOMA．IR呈正相关,与ANP呈负相关。结论脂肪细胞因子参与2型糖尿病、NAFLD病理生理过程,恢复脂肪细胞因子的水平是非常有意义的。     

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate—eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118–125) vs. 114 (108–120) mmHg; P = 0.01] and diastolic [73 (66–80) vs. 67 (70–73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1–9.9) vs. 7.5 (7.2–8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61–3.20) vs. 0.49 (0.31–0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.     

Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.     

Insulin resistance and atherosclerosis in diabetes mellitus

The aim of this study was to test our hypothesis that insulin resistance determines systemic atherosclerosis in type 2 diabetic patients. The design of the study was cross-sectional and included 28 type 2 patients with 48 type 1 patients as controls. The total daily insulin dose required to maintain glycosylated hemoglobin, HbA(1c), at 6.0% for 1 year was used as a measure of long-term insulin resistance. Systemic atherosclerosis was estimated by the toe systolic blood pressure index (TSPI). The results showed that total daily insulin dose was closely and independently associated with TSPI (r =.4652, partial P =.0064) in type 2 diabetic patients with secondary failure, even when adjusted for serum C-peptide (r =.4443, partial P =.00123). The association was absent in type 1 patients. Established risk factors were not associated with TSPI, but the products between individual risk factors and insulin dose were closely associated with TSPI. In conclusion, the daily insulin dose is associated with peripheral atherosclerosis in type 2 diabetic patients with high insulin resistance, but not in type 1 diabetes. The effect is additive to a lesser, underlying effect of established risk factors on atherosclerosis. Longstanding insulin resistance, as estimated by the daily insulin dose, is a determinant of atherogenesis.     

Insulin insensitivity in offspring of parents with type 2 diabetes mellitus

Measurements were made of the plasma glucose and insulin responses to a 75 g oral glucose challenge in 50 Chinese born in Taiwan, divided into two groups on the basis of family history of Type 2 diabetes. Twenty-five individuals (age 29 +/- 5 (+/- SD) years) had 2 parents with normal oral glucose tolerance, whereas at least 1 parent had Type 2 diabetes in the other 25 subjects (age 30 +/- 6 years). In addition, in vivo insulin action was estimated by determining the steady-state plasma glucose concentration during a 3-h continuous infusion of glucose, insulin, and somatostatin. Steady-state plasma glucose concentration was used as a measure of insulin-induced glucose disposal. The 50 subjects were non-obese, and of comparable gender distribution and body mass index. Plasma glucose and insulin concentrations in response to oral glucose were similar in the two groups. However, the steady-state plasma glucose concentration was significantly (p less than 0.01) higher in offspring with a family history of Type 2 diabetes when compared by two-way analysis of variance (mean +/- SE was 5.87 +/- 0.27 vs 5.12 +/- 0.32 mmol l-1). This difference was found despite a significantly (p less than 0.01) higher steady-state plasma insulin concentration during the infusion studies (0.705 +/- 0.027 vs 0.643 +/- 0.025 nmol l-1) in offspring of people with diabetes. The results support the view that resistance to insulin-stimulated glucose uptake is present in offspring of diabetic parents.