脂联素与胰岛素抵抗和2型糖尿病

脂联素是近年运用分子生物学技术发现的新激素。脂联素通过刺激外周组织摄取、氧化游离脂肪酸 ,降低脂肪酸浓度 ,进而改善胰岛素抵抗 ,同时还能抑制动脉粥样硬化的形成。脂联素有望成为治疗糖尿病的新靶点。     

2型糖尿病患者胰岛素抵抗与脂联素、瘦素关系的探讨

目的:通过对2型糖尿病患者血清脂联素、瘦素水平检测及二者之间的比值分析,探讨DM2胰岛素抵抗发生的机理,为临床诊断治疗提供依据。方法:用酶联免疫分析和放射免疫分析对87例DM2,25例DM1患者和30例正常对照者及52例DM2经一年治疗前后脂联素、瘦素水平进行检测分析。结果:DM2患者脂联素水平明显低于DM1和正常对照组(P<0.01);瘦素水平DM1、DM2均高于正常对照组,DM2明显高于DM1(P<0.01);脂联素/瘦素的比值DM1>1(1.183),DM2<1(0.211),DM1与DM2比值比较有显著性差异(P<0.001);52例DM2治疗前后比较,脂联素、瘦素及二者比值有显著差异(P<0.01),脂联素与瘦素比较呈负相关。结论:2型糖尿病胰岛素抵抗的发生与脂联素、瘦素密切相关,二者的比值变化对糖尿病分型具有重要意义。     

抵抗素与2型糖尿病患者胰岛素抵抗的关系

研究血清抵抗素与2型糖尿病(DM)患者胰岛素抵抗(IR)的关系。应用EIA测定72例2型DM患者(非肥胖2型DM组33例,肥胖2型DM组39例)及34名健康者(对照组)的空腹血清抵抗素水平。对照组、肥胖2型DM组及非肥胖2型DM组血清抵抗素水平分别为11.0±6.5μg/L、30.2±9.5μg/L及19.1±8.3μg/L,肥胖2型DM组和非肥胖2型DM组血清抵抗素水平均显著高于对照组(P均<0.001),肥胖2型DM组血清抵抗素水平显著高于非肥胖2型DM组(P<0.001),血清抵抗素水平与2型DM患者HOMAIR指数和程度呈显著正相关(P<0.001)。     

2型糖尿病胰岛素抵抗与阿尔茨海默病

2型糖尿病(type 2 diabetes mellitus,T2DM)是一种复杂而异质的代谢紊乱,可导致不同程度的胰岛素抵抗和B细胞功能障碍.胰岛素抵抗与认知功能障碍之间存在明确的联系,而认知功能障的终点为阿尔茨海默病(Alzheimer's disease,AD).因此,AD和T2DM之间的关键交叉点可能是胰岛素抵...     

脂联素与2型糖尿病相关性的遗传学研究进展

脂联素（ADPN）是脂肪组织特异分泌的一种血浆激素蛋白，其基因定位于3q27，具有降低血糖、血脂及改善胰岛素抵抗的作用，同时也可拮抗动脉粥样硬化的形成。与TNF-α的结构具有同源性但两者生物学效应相反。ADPN结构基因区域内的多态性，ADPN基因突变或表达减少可能与2型糖尿病及其心血管并发症的发病有关。因此脂联素的研究将为临床防治2型糖尿病及其并发症提供新的思路。     

IL-6、TNF-α与2型糖尿病胰岛素抵抗

胰岛素抵抗是是2型糖尿病发生发展的主要因素之一,但胰岛素抵抗产生的分子机制尚不很清楚。大量证据表明炎症因子过多分泌可能在胰岛素抵抗产生中起重要作用。对正常组织中胰岛素抵抗产生机制的认识有助于采取正确的干预措施,最终实现对该疾病的控制。本文主要对炎症因子IL-6,TNF-α与胰岛素抵抗之间的关系进行综述,以期为临床寻找更有效的诊断和治疗手段提供参考。     

2型糖尿病患者血清脂联素与胰岛素抵抗相关性分析

2型糖尿病(DM2)是一种病因尚不完全明了的常见病,胰岛素抵抗(IR)是其发病的主要机理之一.脂联素是脂肪细胞分泌的一种蛋白质,具有影响葡萄糖转运、增强胰岛素敏感性等作用.现有报道,脂联素水平与肥胖、胰岛素抵抗、2型糖尿病紧密相关[1].我们检测了DM2患者的血清脂联素、血脂、胰岛素、血尿酸等,旨在探讨脂联素对DM2患者IR的影响.     

2型糖尿病瘦素、胰岛素含量变化对胰岛素抵抗的影响

瘦素（leptin）与胰岛素（INS）作为胰岛素抵抗的重要因素已为公认。为深入探讨2型糖尿病（DM2）的发病机理与leptin的关系,现将我院自2000年1月-2004年3月的临床观察结果报告如下。     

脂联素与2型糖尿病相关性的遗传学研究进展

脂联素(ADPN)是脂肪组织特异分泌的一种血浆激素蛋白,其基因定位于3q27,具有降低血糖、血脂及改善胰岛素抵抗的作用,同时也可拮抗动脉粥样硬化的形成。与TNF-α的结构具有同源性但两者生物学效应相反。ADPN结构基因区域内的多态性,ADPN基因突变或表达减少可能与2型糖尿病及其心血管并发症的发病有关。因此脂联素的研究将为临床防治2型糖尿病及其并发症提供新的思路。     

2型糖尿病患者合并非酒精性脂肪肝与胰岛素抵抗的相关性

目的研究2型糖尿病合并非酒精性脂肪肝（NAFLD）患者的代谢特征、胰岛功能及胰岛素抵抗水平,并探讨其主要危险因素。方法根据肝脏B超结果,将113例2型糖尿病患者分为NAFLD组和非NAFLD组,比较两组之间的体质指数（BMI）、血脂、血糖、胰岛素、C肽、肝酶、尿酸、胰岛素抵抗、胰岛β细胞功能等指标,并采用Logistic回归分析2型糖尿病患者合并NAFLD的独立危险因素。结果 NAFLD组BMI、甘油三酯（TG）、空腹血糖（FBG）、餐后2h血糖（2hPG）、空腹胰岛素（FIns）和C肽（FCP）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、胰岛素抵抗指数（HOMA-IR）较非NAFLD组均显著升高,而年龄、高密度脂蛋白（HDL）则显著降低。Logistic回归显示年龄、BMI、TG、HOMA-IR与2型糖尿病患者合并NAFLD独立相关（OR=0.95,P=0.024;OR=1.24,P=0.024;OR=2.81,P=0.025;OR=11.96,P=0.001）,其中HOMA-IR是主要的危险因素。结论 2型糖尿病合并非酒精性脂肪肝患者存在更严重的肥胖倾向和代谢紊乱,而胰岛素抵抗是其主要危险因素。     

Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.     

不同治疗方式对新发2型糖尿病患者胰岛β细胞功能及胰岛素抵抗的影响

目的 比较采用胰岛素治疗(INS)与口服降糖药物治疗(OHA)等不同治疗方式对新发2型糖尿病(T2DM)患者胰岛β细胞功能及胰岛素抵抗的影响,推断新发T2DM的最佳治疗方案.方法 将62例新发T2DM患者随机分为胰岛素治疗组(INS组)和口服降糖药物组(OHA组).OHA组首选磺脲类或二甲双胍,或二者合用,疗效欠佳时增加噻唑烷二酮类,一般为2药或3药合用.两组治疗期均为3个月.每组根据血糖调整剂量,目标为空腹血糖(FBG)＜6.0 mmol/L,餐后2h血糖(2hPG)＜8.0mmol/L.观察两组治疗前后FBG、2h PG、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、空腹及餐后2hC肽(FCP、2hCP)水平的变化;用稳态模型(Homa)计算胰岛β细胞功能指数(Homaβ=20×FINS/(FBG-3.5)和胰岛素抵抗指数[HomaIR=(FBG×FINS)/22.5].用治疗后CP、Homaβ、HomaIR等相关指标进行组间比较,以评价胰岛β细胞功能及外周胰岛素抵抗的变化.结果 :(1)治疗后,两组患者FBG、2hPG、HbA1C水平较治疗前均有明显下降(P＜0.01),而在两组间比较差异无统计学意义;(2)治疗后,INS组患者FINS、FCP、2hCP、Homaβ较治疗前升高(P＜0.05),OHA组则无明显变化(P＞0.05),两组间比较差异有统计学意义(P＜0.05);(3)治疗后,INS组患者HomaIR较治疗前有明显下降(P＜0.05),OHA组仅略有下降,两组间比较差异有统计学意义(P＜0.05).结论 早期应用胰岛素治疗可以改善新发T2DM患者胰岛β细胞分泌功能及外周胰岛素抵抗.与OHA相比,INS能更好地保护患者的胰岛B细胞功能.     

Serum leptin levels in gastric cancer patients and the relationship with insulin resistance

Introduction

Serum leptin levels have been examined in various cancers, with conflicting results. However, there is limited information regarding serum leptin levels and insulin resistance in gastric cancer patients. Therefore, we aimed to investigate serum leptin levels, performance status, insulin levels and insulin resistance in patients with gastric cancer. In addition, we examined the relationship between these measurements and leptin levels.

Material and methods

Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in the study. Serum leptin, total protein, albumin, growth hormone, insulin and glucose levels were measured. The homeostasis model assessment (HOMA) was used to assess insulin resistance.

Results

Serum levels of insulin, glucose and growth hormone and insulin resistance were significantly lower in gastric cancer patients than controls (p < 0.05 for all). In the Pearson correlation analysis, insulin resistance was found to be significantly correlated with serum leptin levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a significant negative correlation between performance status and insulin resistance in patients with cachexia (r = –0.512, p = 0.030), while no association was found in non-cachectic patients.

Conclusions

We concluded that serum leptin levels are significantly lower in gastric cancer patients. In addition, gastric cancer patients have decreases in insulin levels, insulin resistance and growth hormone levels. This study found a positive association between serum leptin levels and insulin resistance. Moreover, there is a negative association between serum leptin levels and growth hormone levels. Thus, low insulin and growth hormone levels may suppress the production of leptin in gastric cancer patients.     

抗氧化微量营养素对1型糖尿病大鼠Th2型细胞因子IL-4、IL-10表达的影响

目的:研究抗氧化微量营养素(antioxidantmicronutrients,AM)对1型糖尿病大鼠Th2型细胞因子IL4、IL10基因表达的影响,以探索改善胰岛功能,防止糖尿病发生与发展的营养学因素。方法:应用链脲佐菌素(STZ)小剂量、多次注射法诱导大鼠1型糖尿病模型。AMSe、VE、V、Cr通过饮食方法补充。外周血、脾脏淋巴细胞IL4、IL10基因表达检测应用流式细胞术。血糖及自由基代谢通过生化分析法完成。结果:补充AM组大鼠外周血及脾组织IL4、IL10阳性淋巴细胞百分比明显高于模型对照组(P<0.05,P<0.01),其中Se+VE+V+Cr组升高更明显;糖尿病模型组IL4、IL10表达处于最低水平。补充AM各组较模型组明显增加了胰岛素分泌储备(P<0.05)。与模型组相比,AM补充各组血糖水平显著降低,GSHPx活力水平升高,MDA含量明显下降(P<0.05)。结论:AM最适剂量与组合不仅可以调节糖尿病大鼠胰岛素代谢、减轻氧化侵袭,而且通过上调IL4、IL10等Th2型细胞因子表达减轻胰岛损害。     

2型糖尿病患者血清抵抗素的检测及其与胰岛素抵抗的关系

目的 探讨检测血清抵抗素水平用于2型糖尿病诊断的意义,并分析其与胰岛素抵抗的关系. 方法 随机收集2型糖尿病患者117例、健康对照组109例,测定其空腹血糖、空腹胰岛素和抵抗素水平.比较上述指标在糖尿病患者和健康对照人群之间的差异.分析抵抗素用于糖尿病诊断的灵敏度、特异度、正确率和ROC曲线下面积.应用Pearson直线相关分析计算抵抗素与胰岛素抵抗指数的相关性. 结果 2型糖尿病患者的血清抵抗素、空腹血糖、空腹胰岛素及胰岛素抵抗指数均显著高于健康对照组(P<0.01).抵抗素用于糖尿病诊断的灵敏度为70.09%、特异度为64.22%、正确率为67.30%、ROC曲线下面积为0.695,诊断试验的准确度为中等.糖尿病患者的血清抵抗素水平与其胰岛素抵抗指数呈显著正相关(r=0.803,P<0.01). 结论 2型糖尿病的发生可能与抵抗素水平增高有关.检测血清抵抗素可用于糖尿病的辅助诊断,并可作为评价胰岛素抵抗程度的一种新的敏感指标.     

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective

To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR).

Methods

A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital.A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview.

Results

Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy.

Conclusion

INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin.

Practice implications

Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life.     

Physiological and pathophysiological regulation of regional adipose tissue in the development of insulin resistance and type 2 diabetes

Aim: To survey the latest state of knowledge concerning the regulation of regional adipocytes and their role in the development of insulin resistance and type 2 diabetes. Methods: Data from the English‐language literature on regional adipocytes, including abdominal, intramyocellular, intrahepatic and intra‐islet fat as well as the adipokines and their relations to insulin resistance and type 2 diabetes, were reviewed. Results: It is not the total amount of fat but the fat that resides within skeletal muscle cell (intramyocellular fat), hepatocytes and intra‐abdominally (visceral fat), via systemic and local secretion of several adipokines, that influences insulin resistance. Among the adipokines that relate to insulin resistance, adiponectin and leptin appear to have clinical relevance to human insulin resistance and others may also contribute, but their role is still inconclusive. The intra‐islet fat also adversely affects β‐cell function and number (β‐cell apoptosis), eventually leading to deterioration of glucose tolerance. The abnormal location of fat observed in patients with type 2 diabetes and their relatives is conceivably partly the results of the genetically determined, impaired mitochondrial fatty acid oxidative capacity. Restriction or elimination of the fat load by weight control, regular exercise and thiazolidinediones has been shown to improve insulin resistance and β‐cell function and to delay the development of type 2 diabetes. Conclusion: These data support the plausibility of an essential role of regional adipose tissue in the development of insulin resistance and type 2 diabetes.     

2型糖尿病胰岛素抵抗和胆固醇酯转运蛋白基因多态性的关联研究

目的 探讨胆固醇酯转运蛋白(cholesteyl ester transfer protein，CETP)基因多态性与2型糖尿病胰岛素抵抗的关系。方法 采用聚合酶链反应和酶切电泳方法对108例2型糖尿病患者进行CETP-TaqIB基因型分型，同时测定血脂、空腹胰岛素、胰岛素敏感指数和胰岛素抵抗指数。结果 正常对照组与2型糖尿病组等位基因频率和基因型分布无统计学意义；2型糖尿病甘油三酯(triglyceride，TG)、总胆固醇(total cholesterol，TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol，LDL-C)和载脂蛋白B(apolipoprotein B，apoB)浓度各基因型间差异无统计学意义，而高密度脂蛋白胆固醇(high density lipoprotein cholesterol，HDL-C)、载脂蛋白A1(apolipoprotein A1，apoA1)、空腹胰岛素(fasting insulin，FINS)、胰岛素敏感性指数(insulin sensitivity index，ISI)和HOMA模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance，HOMA-IR)各基因型间差异有统计学意义，HDL-C、apoA，和ISI B2B2型显著高于B1B1型，FINS和HOMA-IR B2B2型显著低于B1B1型；以胰岛素敏感性指数和HOMA-模型胰岛素抵抗指数为因变量进行多元回归分析，ISI和HOMA-IR与体重指数、收缩压、TC、HDL及基因型分型密切相关。结论 CETP-Taq IB基因多态性与2型糖尿病脂代谢及胰岛素抵抗密切关联，可能是胰岛素抵抗的重要遗传因素。     

胃切除术对2型糖尿病患者血糖的影响

目的探讨影响2型糖尿病胃部切除手术后血糖转归的相关因素,为今后此种治疗方法的患者选择提供参考。方法回顾分析2001年1月-2010年12月在北京协和医院行胃部切除手术的45例2型糖尿病患者的临床资料,以术后血糖或抗糖尿病药物用量降低20%为缓解标准,分为缓解组(29例)和无效组(16例),比较两组年龄、体重指数(BMI)、病程和血糖等因素之间的差异。结果 2型糖尿病缓解组病程为5.5±1.7年,显著短于无效组的10.7±2.3年(P<0.05)。缓解组和无效组的年龄和BMI无显著改变。术前兼有高血压者血压亦无明显变化。结论胃部手术治疗2型糖尿病宜选择病程较短(5年以下)者。本研究结果尚需大样本前瞻性研究进行证实。