胰岛素抵抗在2型糖尿病发病机制中的作用

胰岛素抵抗(insulin resistance,IR)又称胰岛素敏感性下降,通常指胰岛素介导的葡萄糖利用率降低。IR是糖尿病的主要发病机制之一,并伴随着糖尿病发生、发展的全过程,其在肥胖、高血压和血脂     

Role of resistin in obesity, insulin resistance and Type II diabetes

Resistin is a member of a class of cysteine-rich proteins collectively termed resistin-like molecules. Resistin has been implicated in the pathogenesis of obesity-mediated insulin resistance and T2DM (Type II diabetes mellitus), at least in rodent models. In addition, resistin also appears to be a pro-inflammatory cytokine. Taken together, resistin, like many other adipocytokines, may possess a dual role in contributing to disease risk. However, to date there has been considerable controversy surrounding this 12.5 kDa polypeptide in understanding its physiological relevance in both human and rodent systems. Furthermore, this has led some to question whether resistin represents an important pathogenic factor in the aetiology of T2DM and cardiovascular disease. Although researchers still remain divided as to the role of resistin, this review will place available data on resistin in the context of our current knowledge of the pathogenesis of obesity-mediated diabetes, and discuss key controversies and developments.     

肥胖及腹型肥胖人群的血清游离脂肪酸水平与胰岛素抵抗的关系研究

目的探讨肥胖及腹型肥胖人群的游离脂肪酸(FFA)水平及糖脂代谢情况,研究肥胖患者FFA与胰岛素抵抗(IR)状态形成的关系。方法按体质量指数(BMI)将560例患者分为肥胖组(BMI≥25kg/m2)及BMI正常对照组(18kg/m2≤BMI25kg/m2),并通过腰围(WC)将BMI正常对照组分为BMI正常非腹型肥胖组和BMI正常腹型肥胖(男WC≥85cm;女WC≥80cm)两个亚组,测量各组身高、体质量、腰围,计算BMI;同时测定血清FFA、脂蛋白(a)[LP(a)]、胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、同型半胱氨酸(HCY)、血糖(GLU)、C肽(CP)、胰岛素(INS)等指标。将各组指标进行比较及相关性分析。结果肥胖组血清FFA水平明显高于BMI正常对照组(P0.01);BMI正常非腹型肥胖组血清FFA水平明显高于BMI正常腹型肥胖组(P0.01);采用Spearman相关分析显示,正常对照组的血清FFA水平与LP(a)、INS呈正相关,BMI正常的腹型肥胖组血清FFA水平与BMI、LP(a)、TG、CP、INS呈正相关,肥胖组的血清FFA水平与BMI、LP(a)、TG、LDL-C、CP、INS呈正相关。结论血清FFA是肥胖及腹型肥胖患者体内参与IR的重要环节及因素。     

男性腹型肥胖患者腹部脂肪面积与胰岛素抵抗的相关性分析

目的：探讨男性腹型肥胖患者腹部脂肪面积与糖代谢指标的关系。方法选择21～62岁肥胖男性94例,其中腹围≥90 cm（腹型肥胖组）70例,＜90 cm（均匀肥胖组）24例,登记两组患者的一般资料,测量身高、体质量、腹围、臀围,计算体质量指数（BMI）;受试者空腹行口服葡萄糖耐量试验,检测血糖（0、1、2 h）及胰岛素（0、1、2 h）,计算胰岛素抵抗指数;应用 MRI 测量腹部内脏脂肪面积;比较两组患者血糖、胰岛素及胰岛素抵抗指数的差异,并分析腹型肥胖患者糖代谢相关指标与腹部脂肪面积的相关性。结果腹型肥胖组 BMI、腰围、臀围、胰岛素抵抗指数及腹部脂肪面积均高于均匀肥胖组[（28.67±4.20）、（21.80±1.97）kg/ m2,（99.75±4.07）、（79.50±10.05）cm,（104.42±7.62）、（91.86±4.49）cm,2.60±1.80、1.52±0.73,（153.06±53.23）、（71.78±25.48）cm2],差异均有统计学意义（t值分别为-7.704、-9.583、-7.618、-2.877、-7.184,P 均＜0.05）;腹型肥胖组0、1、2 h 血糖和胰岛素高于均匀肥胖组[（5.89±1.36）、（5.29±0.53）mmol/ L,（10.55±3.07）、（8.76±1.96）mmol/ L,（8.41±3.63）、（6.54±1.50）mmol/ L,（9.71±5.05）、（6.42±2.96）mU/ L,（83.29±64.51）、（33.00±19.82） mU/ L,（27.93±14.98）、（63.56±21.09）mU/ L],差异均有统计学意义（t 值分别为-2.098、-2.671、-2.447,-3.010、-3.784、-3.089,P 均＜0.05）;腹型肥胖患者腹部脂肪面积与年龄、BMI、腹围、臀围、血糖（0、1、2 h）、胰岛素（0、2 h）及胰岛素抵抗指数均呈正相关（ r 值分别为0.254、0.533、0.521、0.615、0.245、0.315、0.294、0.273、0.249、0.225,P 均＜0.05）,校正混杂因素后,年龄（x1）、腹围（x2）及胰岛素抵抗指数（x 3）与腹部内脏脂肪面积成正相关相关（y =1.369x1＋4.472x2＋25.072x3-333.626）。结论与均匀肥胖相比较,腹型肥胖患者的腹部脂肪面积大小与胰岛素抵抗相关。     

Role of impaired insulin secretion and insulin resistance in the pathogenesis of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a heterogenous disorder caused by a combination of genetic and acquired abnormalities that affect insulin sensitivity and insulin secretion. Currently available data suggest that insulin resistance is the acquired defect largely secondary to unhealthy lifestyles and that the major genetic factor is impaired insulin secretion. The latter is the result of both reduced β-cell mass and functional abnormalities makes the β-cell unable to compensate for increased insulin requirements caused by insulin resistance. Targeting both insulin resistance and impaired insulin secretion is therefore appropriate to prevent T2DM and to improve glycemic control in those with the disorder. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.     

多囊卵巢综合征患者胰岛素抵抗与肥胖的研究和分析

目的:调查多囊卵巢综合征患者胰岛素抵抗的特点,并分析其相关因素,为多囊卵巢综合征的治疗和病因研究提供临床依据.方法:根据体质量指数将276例多囊卵巢综合征患者分为肥胖组和非肥胖组,对比两组患者胰岛素抵抗、糖耐量受损、 胰岛素曲线下面积与性激素水平的相关性.结果:(1)胰岛素抵抗与糖耐量受损不完全一致. (2)肥胖组多囊卵巢综合征患者胰岛素抵抗患病率明显高于非肥胖组多囊卵巢综合征患者(P＜0 05),且肥胖组多囊卵巢综合征患者月经周期更长.(3)胰岛素曲线下面积与睾酮水平正相关,与黄体生成素/卵泡刺激素比值负相关.结论:胰岛素抵抗是多囊卵巢综合征患者的重要症状之一,肥胖组多囊卵巢综合征患者胰岛素抵抗的患病率高于非肥胖组,差异有统计学意义(P＜0.05).肥胖是多囊卵巢综合征患者的重要危险因素,可以加重多囊卵巢综合征的症状.     

胰岛素抵抗与肥胖的关系认识

肥胖是由体内热量摄入大于消耗,造成脂肪在体内聚集过多,导致体重超常的疾患。肥胖常以体质指数(BMI)确定。WHO规定以BMI≥25kg/m2为超重,≥30kg/m2为肥胖。根据脂肪组织的分布特     

Role of visfatin in obesity-induced insulin resistance

The growing worldwide burden of insulin resistance (IR) emphasizes the importance of early identification for improved management. Obesity, particularly visceral obesity, has been a key contributing factor in the development of IR. The obesity-associated chronic inflammatory state contributes to the development of obesity-related comorbidities, including IR. Adipocytokines, which are released by adipose tissue, have been investigated as possible indicators of IR. Visfatin was one of the adipocytokines that attracted attention due to its insulin-mimetic activity. It is released from a variety of sources, including visceral fat and macrophages, and it influences glucose metabolism and increases inflammation. The relationship between visfatin and IR in obesity is debatable. As a result, the purpose of this review was to better understand the role of visfatin in glucose homeostasis and to review the literature on the association between visfatin levels and IR, cardiovascular diseases, and renal diseases in obesity.     

胰岛素抵抗在脑梗死发病中的作用

目的 探讨胰岛素抵抗和高胰岛素血症在脑梗死发病中的作用。方法 检测单纯性脑梗死(排除了高血压、冠心病、糖尿病、肥胖)41例和对照组 15例的血糖、血清胰岛素和血脂变化。结果脑梗死组(动脉粥样硬化性脑梗死组25例,腔隙性脑梗死组 16例)的胰岛素水平、I/G 及其曲线下面积均有显著性增高。结论 胰岛素抵抗和高胰岛素血症可能是脑梗死的一个独立危险因素。     

男性肥胖患者胰岛素抵抗与瘦素抵抗的相关性分析

目的　探讨男性肥胖者瘦素抵抗与胰岛素瘦素抵抗的相关性。方法　 35例肥胖男性和 30例正常对照组均进行葡萄糖耐量试验 ,空腹血清瘦素及胰岛素采用放射免疫法。空腹血糖及餐后 2h血糖采用氧化酶法 ,同时测每例受试者身高、体重 ,计算体重指数 (BMI =体重 /身高2 )。结果　肥胖组空腹血清瘦素(14 92± 10 38pmol/L)与对照组 (6 6 5± 2 73pmol/L)相比差异有显著意义 (P <0 0 1) ,肥胖组空腹血清胰岛素水平 (11 2 6± 3 90mIU/L)与健康对照组 (6 73± 2 4 8mIU/L)相比差异也有显著意义 (P <0 0 1) ,两组空腹血糖差异无显著意义 ;肥胖组内空腹瘦素与胰岛素相关分析显示两者呈显著正相关 (r =0 5 75 ,P <0 0 1)。结论　肥胖患者存在瘦素抵抗及胰岛素抵抗 ,且瘦素抵抗与胰岛素抵抗显著正相关     

Role of resistin in diet-induced hepatic insulin resistance

Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated with an approximately 80% increase in plasma resistin levels. In particular, the rate of endogenous glucose production (GP) increased more than twofold compared with that in mice fed a standard chow. Treatment with the resistin ASO for 1 week normalized the plasma resistin levels and completely reversed the hepatic insulin resistance. Importantly, in this group of mice, the acute infusion of purified recombinant mouse resistin, designed to acutely elevate the levels of circulating resistin up to those observed in the HF-fed mice, was sufficient to reconstitute hepatic insulin resistance. These results provide strong support for a physiological role of resistin in the development of hepatic insulin resistance in this model.     

肥胖所导致的胰岛素抵抗分子机制的研究进展

胰岛素抵抗(IR)可以定义为病理生理条件下,正常水平的胰岛素不足以使胰岛素作用的靶组织产生正常的生理效应。肥胖及身体脂肪组织的扩张可使IR的发生率增加。肥胖是心血管疾病和肝脏疾病发生的共同基础,常常是高脂血症和2型糖尿病发病的前奏。肥胖诱导的高游离脂肪酸(FFA)水平、炎症和氧化应激在IR的发生、发展中扮演重要角色。     

成纤维细胞因子21同腹型肥胖者颈动脉内膜中层厚度及胰岛素抵抗关系的研究

目的探讨腹型肥胖者成纤维细胞因子21(FGF21)同颈动脉内膜中层厚度(IMT)及胰岛素抵抗(IR)的关系。方法在体检人员中选择腹型肥胖者90例,并根据颈动脉IMT将其90例分为IMT增厚组(A组)和IMT正常组(B组),并选择90例健康者(C组)进行比较,分别进行FGF21、稳态胰岛素评价指数(HOMA-IR)等参数测定。结果A组的颈动脉IMT、ln(HOMA-IR)和FGF21均分别高于B组和C组,差异有统计学意义(P0.05);颈动脉IMT和ln(HOMA-IR)(r=0.611,P0.01)、FGF21(r=0.464,P0.01)、TC(r=0.370,P0.05)、收缩压(r=0.276,P0.05)呈正相关。FGF21水平同BMI(r=0.454,P0.01)、WHR(r=0.353,P0.01)、TG(r=0.266,P0.05)、ln(HOMA-IR)(r=0.223,P0.05)、空腹胰岛素水平(r=0.220,P0.05)呈正相关。Logistic回归分析结果显示,FGF21、收缩压、ln(HOMA-IR)为动脉粥样硬化的独立危险因素(P0.05)。结论肥胖者颈动脉IMT已有所升高,FGF21可能对预测肥胖者早期的动脉粥样硬化有重要意义。     

Metabolic syndrome and insulin resistance in migraine

Metabolic syndrome is associated with migraine but there is no study comparing the characteristics of migraine with and without metabolic syndrome from Southeast Asia. This study was therefore undertaken to compare the clinical characteristics of migraine in patients with and without metabolic syndrome and insulin resistance. 135 consecutive patients with migraine diagnosed on the basis of International Headache Society criteria were subjected to clinical evaluation as per fixed protocol. Headache severity, frequency and functional disability were recorded. Metabolic syndrome was diagnosed as per National Cholesterol Education Programme: Adult Treatment Panel III and International Diabetic Federation criteria. Insulin resistance was calculated by homeostases model assessment. Their age ranged between 14 and 61 years and 108 were females. Metabolic syndrome was present in 31.9% patients and only 13 were obese. Insulin resistance was present in 11.1%. Metabolic syndrome was correlated with age, gender, number of triggers, years of headache and duration of migraine attacks. Insulin resistance correlated with duration of migraine attacks. From this study, it can be concluded that metabolic syndrome was present in 31.9% of the migraineurs which was mainly in elderly who had longer duration of headache and multiple triggers.     

Relationship between serum lipoprotein ratios and insulin resistance in obesity

BACKGROUND: The fasting serum lipid profile [triglycerides (TGs), total cholesterol (TC), and LDL- and HDL-cholesterol (LDL-C and HDL-C)] is used to calculate lipid ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) that allow identification of individuals at increased risk for cardiovascular disease. Because these individuals are also frequently insulin resistant, this study analyzed the relationships between lipid ratios and insulin sensitivity. METHODS: In 132 obese [mean (SE) body mass index, 37.5 (0.6) kg/m(2)] outpatients without known diabetes mellitus, fasting serum lipid profiles and 75-g oral glucose tolerance tests were performed. Insulin sensitivity was assessed from surrogate estimates for fasting (QUICKI) and dynamic (OGIS) conditions. RESULTS: After exclusion of other endocrine diseases (n = 35), the remaining patients were classified as glucose tolerant (n = 56), glucose intolerant (n = 22), or as having type 2 diabetes (n = 19). QUICKI and OGIS indicated severe insulin resistance in all individuals with type 2 diabetes and impaired glucose tolerance compared with glucose-tolerant individuals: QUICKI, glucose tolerant, 0.302 (0.002); glucose intolerant, 0.290 (0.002); type 2 diabetes, 0.281 (0.005); P <0.001; OGIS (mL . m(-2) . min(-1)), glucose tolerant, 343 (7), glucose intolerant, 293 (9); type 2 diabetes, 256 (12); P <0.001. Serum TG (P <0.005) and TG/HDL-C ratios (P <0.05) were increased in individuals with impaired glucose tolerance. TG/HDL-C ratios negatively correlated with QUICKI (r = -0.370; P < 0.001) and OGIS (r = -0.333; P < 0.005) in nondiabetic individuals (glucose tolerant plus glucose intolerant), but not in patients with type 2 diabetes (not significant). CONCLUSIONS: This study demonstrates that the TG/HDL-C ratio positively correlates with insulin resistance in severely obese nondiabetic individuals.     

Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice

Null mutations of the proopiomelanocortin gene (Pomc) cause obesity in humans and rodents, but the contributions of central versus pituitary POMC deficiency are not fully established. To elucidate these roles, we introduced a POMC transgene (Tg) that selectively restored peripheral melanocortin and corticosterone secretion in Pomc mice. Rather than improving energy balance, the genetic replacement of pituitary POMC in PomcTg mice aggravated their metabolic syndrome with increased caloric intake and feed efficiency, reduced oxygen consumption, increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance. Pair-feeding of PomcTg mice to the daily intake of lean controls normalized their rate of weight gain but did not abolish obesity, indicating that hyperphagia is a major but not sole determinant of the phenotype. Replacement of corticosterone in the drinking water of Pomc mice recapitulated the hyperphagia, excess weight gain and fat accumulation, and hyperleptinemia characteristic of genetically rescued PomcTg mice. These data demonstrate that CNS POMC peptides play a critical role in energy homeostasis that is not substituted by peripheral POMC. Restoration of pituitary POMC expression to create a de facto neuronal POMC deficiency exacerbated the development of obesity, largely via glucocorticoid modulation of appetite, metabolism, and energy partitioning.