2型糖尿病患者血清抵抗素浓度与血脂代谢水平的临床意义

目的了解2型糖尿病患者血清抵抗素浓度与空腹血糖、血脂的关系。方法选择52例2型糖尿病患者和40例健康中老年人,分别分为糖尿病组和非糖尿病组,用竞争性酶联免疫吸附法测定各组空腹血浆抵抗素水平,同时检测空腹血糖、血脂各项指标。结果糖尿病空腹血浆抵抗素水平显著高于对照组(p<0.05)。抵抗素与甘油三脂、空腹血糖呈正相关关系(r=0.687,p<0.05,r=0.849,p<0.05),而抵抗素与其余各项血脂指标、性别之间无明显相关性。结论血清抵抗素水平与2型糖尿病关系密切,抵抗素水平可能影响体内能量代谢和平衡,与糖、脂代谢的关系更为密切。     

From obesity to diabetes

The major risk factor for the development of insulin resistance and type 2 diabetes is obesity. A key role is the new understanding of adipocytes as an endocrine system. Adipocytes secrete numerous substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. There is also a role of free fatty acids by blocking directly intracellular metabolism of glucose and by their lipotoxicity. The pre-receptor metabolism of cortisol may be enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. The new class of thiazolidinediones (glitazones), binding to the peroxisome proliferator activated receptor (PPAR-gamma) lowers the levels of resistin and increases adiponectin, resulting in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance should be an attempt to reduce body weight and to increase physical activity. These are successful means to avoid the development of type 2 diabetes from prediabetic states, as shown recently in 3 independent intervention trials.     

抵抗素与老年糖尿病合并高血压的相关性研究

目的 探讨抵抗素对老年糖尿病合并高血压的影响及其与相关代谢指标的关系.方法 将153例2型糖尿病分为合并高血压组70例和单纯糖尿病组83例,并选取同期健康体检55例老年人作为健康对照组.均测定体质量指数（BMI）、空腹血糖（FBG）、餐后2h血糖（2 h PG）、空腹胰岛素（FINS）、糖化血红蛋白（HbA1c）、胰岛素抵抗指数（HOMA-IR）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）及抵抗素水平,分析抵抗素与其他各项代谢指标的相关性.结果 与健康对照组比较,合并高血压组和单纯糖尿病组2hPG、BMI、FBG、FINS、HOMA-IR、HbA1c、TG及血清抵抗素水平均明显升高,HDL-C明显下降,差异均有统计学意义（P ＜0.01,P＜0.05）;与单纯糖尿病组比较,合并高血压组HOMA-IR、血清抵抗素水平明显升高,差异有统计学意义（P＜0.05）;血清抵抗素水平与BMI、HOMA-IR呈显著正相关（r =0.278,P=0.034;r =0.492,P=0.000）.结论 老年2型糖尿病合并高血压患者血清抵抗素水平明显升高,提示血清抵抗素可能通过某种机制和途径促进糖尿病患者的动脉硬化进程,促发高血压.     

Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients

Introduction  

Blood glucose levels and insulin resistance in critically ill patients on admission to intensive care units (ICUs) have been identified as factors influencing mortality. The pathogenesis of insulin resistance (IR) in critically ill patients is complex and not fully understood. Resistin is a hormone mainly derived from macrophages in humans and from adipose tissue in rodents, which regulates glucose metabolism and insulin sensitivity. In non-critically ill patients, resistin was found to be related to impaired glucose tolerance, insulin resistance, metabolic syndrome, obesity and type 2 diabetes. Therefore, resistin might represent a link between inflammation, acute phase response and insulin resistance in critically ill patients. We aimed to examine the correlation of serum resistin concentrations to parameters of inflammation, organ function, metabolism, disease severity and survival in critically ill patients.     

2型糖尿病患者血清抵抗素水平的变化研究

目的探讨人血清抵抗素水平与2型糖尿病的关系.方法 2型糖尿病患者48例和正常对照组47例,采用酶联免疫分析法检测空腹血清抵抗素、胰岛素水平;同时测血糖、血压、血脂、身高、体重,计算腰围、臀围、体重指数、腰臀比值和胰岛素敏感指数、胰岛素抵抗性、胰岛B细胞功能.结果 2型糖尿病组的体重指数、甘油三酯、血清抵抗素水平显著高于正常对照组（P＜0.05）;相关分析显示血清抵抗素水平与体重指数、腰围、空腹胰岛素、血压呈正相关.在正常对照组,血清抵抗素水平与胰岛素敏感指数、胰岛素抵抗性、胰岛B细胞功能相关.而且血清抵抗素水平在糖尿病肥胖组显著高于糖尿病非肥胖组和正常对照组（P＜0.05）.结论 2型糖尿病患者血清抵抗素水平升高,与肥胖相关,血清抵抗素可能是联系肥胖和2型糖尿病的重要因素.     

老年2型糖尿病患者血清抵抗素、游离脂肪酸水平研究

目的探讨血清抵抗素、游离脂肪酸与老年糖尿病及胰岛素抵抗的关系。方法测量老年(年龄>60岁)2型糖尿病患者82例(老年糖尿病组),成年(年龄<60岁)2型糖尿病患者70例(成年糖尿病组),老年健康体检者50例(对照组)空腹血清抵抗素、游离脂肪酸、空腹血糖及胰岛素水平,计算胰岛素抵抗指数。结果老年糖尿病组血清抵抗素、游离脂肪酸水平高于对照组与成年糖尿病组(P<0.05或P<0.01)。老年糖尿病组胰岛素抵抗程度较成年糖尿病组明显,并伴有脂代谢紊乱。结论血清抵抗素、游离脂肪酸与老年糖尿病尤其是老年胰岛素抵抗密切相关。     

Treatment of noninsulin-dependent diabetes mellitus with enzyme inducers

Although treated adequately with antidiabetic drugs, diet, exercise, and education, patients with noninsulin-dependent diabetes mellitus (NIDDM) may develop resistance to treatment. In NIDDM hepatic microsomal enzyme activity is reduced and since postreceptional glucose metabolism is influenced by these enzymes, we treated the subjects with enzyme-inducing drugs. These inducers (phenobarbital and medroxyprogesterone acetate) when added as adjuvant therapy to sulfonyl urea regimen, reduced blood glucose and plasma insulin, and increased microsomal enzyme activity (as indicated by increased antipyrine metabolism). A trial with placebo did not alter serum glucose levels. Body weight fell and serum aminotransferase levels were normalized. These changes were reflected by reduction of liver fat content (determined by light microscopy), by increased surface density of smooth endoplasmic reticulum, and by repairation of the plasma cell membrane of hepatocytes, as seen in electron micrographs. Activation of postreceptional events in hepatocytes may thus be a new approach in the treatment of therapy-resistant type II diabetes.     

Pathogenesis of type 2 diabetes mellitus

This article provides an overview of the pathogenesis of type 2 diabetes mellitus. Discussion begins by describing normal glucose homeostasis and ingestion of a typical meal and then discusses glucose homeostasis in diabetes. Topics covered include insulin secretion in type 2 diabetes mellitus and insulin resistance, the site of insulin resistance, the interaction between insulin sensitivity and secretion, the role of adipocytes in the pathogenesis of type 2 diabetes, cellular mechanisms of insulin resistance including glucose transport and phosphorylation, glycogen and synthesis,glucose and oxidation, glycolysis, and insulin signaling.     

Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production

The adipose-derived hormone resistin is postulated to link obesity to insulin resistance and diabetes. Here, the infusion of either resistin or the resistin-like molecule-beta (RELMbeta) rapidly induced severe hepatic but not peripheral insulin resistance. In the presence of physiologic hyperinsulinemia, the infusion of purified recombinant resistin, increasing circulating resistin levels by approximately twofold to 15-fold, inhibited glucose metabolism such that lower rates of glucose infusion were required to maintain the plasma glucose concentration at basal levels. The effects of resistin and RELMbeta on in vivo insulin action were completely accounted for by a marked increase in the rate of glucose production. These results support the notion that a novel family of fat- and gut-derived circulating proteins modulates hepatic insulin action.     

Associations of resistin with inflammation and insulin resistance in patients with type 2 diabetes mellitus

OBJECTIVE: Resistin has been linked to obesity, type 2 diabetes, inflammation and atherosclerosis but the results of animal and human studies have been at variance. The purpose of this study was to investigate the potential roles of resistin in patients with type 2 diabetes and to evaluate the correlation between resistin and markers of obesity, inflammation, insulin resistance, metabolic parameters, diabetes control and complications. MATERIAL AND METHODS: Fasting resistin, leptin, insulin, glucose, HbA1c, full lipid profile, C-reactive protein (CRP) (high sensitivity assay) and complete blood count were determined in 135 patients with type 2 diabetes. Univariate regression and multivariate logistic regression analyses were used to relate resistin with indices of obesity, inflammation, insulin resistance (homeostasis model, HOMA), insulin sensitivity, diabetic control, coronary heart disease (CHD) and degree of microalbuminuria. RESULTS: Resistin showed significant (p<0.05) correlations with body mass index (BMI) "(Spearman r=0.67), waist circumference (r=0.54), fasting insulin (0.51), insulin sensitivity (r=-0.29), HOMA (r=0.30), leptin (r=0.39), CRP (r=0.29), white cell count (r=0.25) and lipid parameters but showed no significant correlation with glucose and HbA1c. Partial correlation analysis, with correction for BMI, abolished the correlation of resistin with insulin sensitivity and HOMA but not with the white cell count. When confounding factors were fixed using multiple logistic regression, resistin was not independently associated with CHD (odds ratio=1.05, p=0.08) and degree of microalbuminuria (odds ratio=1.06, p=0.24). CONCLUSIONS: Resistin showed significant BMI-dependent associations with insulin resistance and factors linked with obesity and inflammation in patients with type 2 diabetes. Resistin may represent a link between obesity and insulin resistance via pro-inflammatory pathways.     

腹部和大腿皮下脂肪组织抵抗素蛋白的表达

背景:抵抗素是脂肪细胞分泌的一种多肽激素。而中心性肥胖时可引起胰岛素抵抗和导致2型糖尿病。目的:比较正常人腹部和大腿皮下脂肪组织抵抗素蛋白表达的情况,探讨抵抗素在中心性肥胖引起胰岛素抵抗中的作用。设计:对照观察实验。单位:华中科技大学同济医学院附属同济医院内分泌科。对象:选择2003-01/04华中科技大学同济医学院附属同济医院外科住院患者20例,根据留取脂肪组织的部位分腹部皮下脂肪组织组12例和大腿皮下脂肪组织组8例。方法:①所有患者测量血压、身高、体质量,计算体质量指数,体内脂肪百分比(按白种人数据推导的公式):男性=1.2×体质量(kg) 身高-2(m-2) 0.23×年龄-16.2;女性=1.2×体质量(kg) 身高-2(m-2) 0.23×年龄-5.4。②葡萄糖氧化酶法测定空腹血糖。③留取的脂肪组织标本用单去污裂解液提取脂肪组织中的蛋白质,考马斯亮蓝法测定蛋白质浓度,Western-blot测量脂肪组织抵抗素蛋白的表达水平。主要观察指标:两组患者的血压、体质量指数,体内脂肪百分比,空腹血糖,抵抗素蛋白的表达水平。结果:纳入患者20例,均进入结果分析。①两组的空腹血糖、收缩压、舒张压、体质量指数、体内脂肪百分比差异无显著性(P>0.05)。②腹部皮下脂肪组织抵抗素蛋白表达(A)为14942±6076,明显高于大腿皮下脂肪组织组39421±6087,二者比较差异显著(P<0.01)。结论:抵抗素蛋白在腹部皮下脂肪组织的表达高于腿部皮下脂肪组织,此结果对中心性肥胖并引起胰岛素抵抗和2型糖尿病的发生具有参考价值。     

Peripheral glucose homeostasis: does brain insulin matter?

Much controversy surrounds the relative role of insulin signaling in the brain in the control of hepatic glucose metabolism. In this issue of the JCI, Ramnanan and colleagues demonstrate that arterial infusion of insulin into the brains of dogs reduces net hepatic glucose output without altering endogenous glucose production. However, this effect was modest and required both prolonged fasting and prolonged exposure of the brain to insulin, raising doubts about the overall physiological relevance of insulin action in the brain on hepatic glucose metabolism. Given the dominant direct role that insulin plays in inhibiting glucose production in the liver, we suggest that the main effect of central insulin on hepatic glucose metabolism may be more chronic and assume greater significance either when portal insulin is deficient, as occurs during exogenous insulin treatment of type 1 diabetes, or when chronic hyperinsulinemia and central insulin resistance develops, as occurs in type 2 diabetes.     

Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes

BACKGROUND: Protein phosphatase 2A (PP2A) acts on a number of enzymes involved in the insulin regulation of glucose uptake and glycogen synthesis. This study was carried out to investigate the effect of insulin on PP2A expression in skeletal muscles of type 2 diabetic and control subjects. MATERIAL AND METHODS: Ten type 2 diabetic and 10 matched, control subjects were studied using the euglycaemic-hyperinsulinaemic clamp technique combined with indirect calorimetry. Immunoreactive protein levels of the catalytic alpha subunit of PP2A (PP2A-C alpha) were measured in biopsies from the vastus lateralis muscle obtained in the basal and insulin-stimulated state. RESULTS: In type 2 diabetic subjects insulin-mediated glucose disposal, glucose oxidation and nonoxidative glucose metabolism were reduced, whereas lipid oxidation was increased (all P < 0.05). Insulin down-regulated PP2A-C alpha expression in skeletal muscle of the control subjects (P < 0.05) but not in the type 2 diabetic subjects. In the control subjects, the insulin-mediated decrease in PP2A-C alpha correlated with the insulin-mediated increase in glucose disposal, glucose oxidation, nonoxidative glucose metabolism (all P < 0.05) and decrease in lipid oxidation (P < 0.01). In the type 2 diabetic subjects these relationships were absent. CONCLUSIONS: Down-regulation of PP2A-C alpha expression by insulin in skeletal muscle seems to be associated with a normal insulin action on glucose storage, glucose and lipid oxidation. Impaired down-regulation of PP2A-C alpha expression by insulin may be a marker for insulin resistance and contribute to the pathogenesis of type 2 diabetes.     

AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice

Diabetes mellitus (DM) derives from either insulin deficiency (type 1) or resistance (type 2). Insulin regulates glucose metabolism and homeostasis by binding to a specific membrane receptor (IR) with tyrosine kinase activity, expressed by its canonical target tissues. General or tissue-specific IR ablation in mice results in complex metabolic abnormalities, which give partial insights into the role of IR signaling in glucose homeostasis and diabetes development. We generated a chimeric IR (LFv2IRE) inducible on administration of the small molecule drug AP20187. This represents a powerful tool to induce insulin receptor signaling in the hormone target tissues in DM animal models. Here we use adeno-associated viral (AAV) vectors to transduce muscle and liver of nonobese diabetic (NOD) mice with LFv2IRE. Systemic AP20187 administration results in time-dependent LFv2IRE tyrosine phosphorylation and activation of the insulin signaling pathway in both liver and muscle of AAV-treated NOD mice. AP20187 stimulation significantly increases hepatic glycogen content and muscular glucose uptake similarly to insulin. The LFv2IRE-AP20187 system represents a useful tool for regulated and rapid tissue-specific restoration of IR signaling and for dissection of insulin signaling and function in the hormone canonical and noncanonical target tissues.     

二甲双胍治疗对肥胖2型糖尿病患者血清中抵抗素、胰岛素样生长因子Ⅰ水平的影响

目的：检测新诊断的肥胖2型糖尿病人群经单用二甲双胍治疗前后抵抗素、胰岛素样生长因子Ⅰ（ IGF-Ⅰ）及炎症因子的变化,探讨二甲双胍改善胰岛素抵抗及预防肿瘤发生的分子机制。方法选取新诊断的肥胖2型糖尿病人56例及健康对照50例,经饮食及运动治疗1周后给予二甲双胍1500 mg/d,治疗3个月,给药前后分别抽取空腹静脉血,测定空腹血糖、空腹胰岛素、糖化血红蛋白、抵抗素、IGF-Ⅰ、白细胞介素-6（IL-6）和超敏的C反应蛋白（sCRP）,应用稳态模型评估法评价胰岛素抵抗指数（HOMA-IR）。治疗前后的比较及组间的比较采用t检验及单因素方差分析。多因素的分析采用多元回归分析。结果二甲双胍治疗前后空腹血糖、空腹胰岛素、HOMA-IR、糖化血红蛋白、抵抗素、IGF-Ⅰ、IL-6和sCRP 明显下降（ P＜0.05）,但仍高于正常对照组（ P＜0.05）。抵抗素、IL-6和sCRP与胰岛素抵抗指数呈正相关（ r＝0.95,0.89,0.78,P＜0.01）,是后者的独立影响因素（β＝1．91,0.148,1．6,P＝0.000）;空腹胰岛素与IGF-Ⅰ呈正相关（r＝0.91,P＜0.01）,是IGF-Ⅰ的独立影响因素（β＝4．30,P＝0.000）。结论新诊断的肥胖2型糖尿病给予二甲双胍治疗后可能通过降低抵抗素及炎症因子的水平,改善胰岛素抵抗,从而降低了血清胰岛素和IGF-Ⅰ的水平。     

罗格列酮对2型糖尿病患者血浆C反应蛋白和纤溶酶原激活剂抑制剂(PAI1)活性的影响

血清C反应蛋白(CRP)是机体受到各种损伤或发生炎症反应后的一种急性期反应蛋白。近年来研究发现其本身还具有促进炎症反应及动脉粥样斑块破裂,促发局部血栓形成的作用。CRP还与肥胖、2型糖尿病及冠心病有关,对这组疾病的未来风险预测及临床治疗有效性的评估具有一定价值[1]。研     

Changes in muscle glucose metabolism in type 1 diabetes

Patients with type 1 diabetes are characterized by an average 40% reduction in the insulin sensitivity. In newly diagnosed patients, insulin resistance is due to insulin deficiency and its metabolic consequences. After the beginning of insulin therapy, insulin sensitivity transiently improves, but deteriorates again after 6-9 months of insulin therapy. Insulin resistance is mainly due to a reduction in glucose uptake by muscle tissue. There are similar relative reductions in both oxidative and nonoxidative glucose disposal. When glucose disposal is determined under similar plasma glucose and insulin concentrations, glucose oxidation, the activity of pyruvate dehydrogenase and glycogen synthase are all reduced. If glucose disposal rate in diabetic patients is normalized by glucose mass action, both oxidative and nonoxidative glucose disposal and glycogen synthase activity become normal. As the normalization of glucose disposal occurs in the face of unchanged muscle glucose-6-phosphate concentrations, this suggest that reduced glucose disposal is secondary to reduced glucose transport in type 1 diabetes.