血游离脂肪酸与不稳定心绞痛病人胰岛素抵抗的关系

目的探讨无糖尿病的不稳定心绞痛患者血浆游离脂肪酸(freefattyacids,FFA)与胰岛素抵抗(insulinresistance,IR)的关系。方法不稳定心绞痛组为经冠状动脉造影确诊不稳定型心绞痛的无糖尿病患者42例,对照组为经冠状动脉造影排除了冠心病患者30例,行75g葡萄糖口服耐量试验,分别测定空腹、餐后30min、120min血糖、胰岛素及FFA水平。结果伴IR患者在不稳定心绞痛组26例(26/42),对照组为12例(12/30),(P=0.066);在不稳定心绞痛组,伴IR患者空腹和餐后120min,FFA分别为(0.63±0.16)mmol/L和(0.16±0.07)mmol/L;高于无IR患者,空腹和餐后120min值为(0.48±0.21)mmol/L和(0.07±0.06)mmol/L(P<0.05);稳态模型评估胰岛素抵抗(homeostasismodelassay-insulinresistanceindex,HOMA-IR)增高(0.50±0.20与0.36±0.22,P<0.05),胰岛素敏感指数(insulinsensitivityindex,HOMA-ISI)降低(-1.96±0.20与-1.71±0.22,P<0.05);不稳定心绞痛组和对照组伴IR患者比较,FFA明显高于对照组,分别为[(0.63±0.16)mmol/L与(0.48±0.22)mmol/L,P<0.05,(0.16±0.07)mmol/L与(0.08±0.03)mmol/L,P<0.01]。相关分析显示HOMA-IR与体重指数呈正相关(r=0.51,P<0.01);餐后30minFFA与HOMA-IR呈正相关(r=0.44,P<0.05);餐后120minFFA分别与空腹胰岛素(r=0.55,P<0.05)、餐后120min血糖呈正相关(r=0.432,P<0.05);游离脂肪酸曲线下面积(FFAAUC)与HOMA-IR(r=0.492,P<0.05)、体重指数(r=0.94,P<0.0001)、腰围(r=0.41,P<0.05)、臀围(r=0.40,P<0.05)和餐后120min胰岛素(r=0.90,P<0.0001)呈正相关。多重逐步回归分析显示,HOMA-IR与体重指数、餐后120minFFA呈正相关。结论FFA与无糖尿病的不稳定心绞痛患者胰岛素抵抗存在密切关系,餐后120minFFA有可能作为评价这类患者胰岛素抵抗的间接辅助诊断指标。     

高血压合并代谢综合征患者血清脂联素与游离脂肪酸谱等代谢参数关系研究

目的 研究原发性高血压合并代谢综合征和未合并代谢综合征患者血清脂联素水平、游离脂肪酸谱特征及与其他糖脂代谢参数间关系.方法 用放射免疫分析法测定128例高血压合并或未合并代谢综合征患者与43例正常对照组血清脂联素,同时用气相色谱/质谱测定其游离脂肪酸成分.结果 高血压合并代谢综合征患者血清脂联素低于未合并代谢综合征组和正常对照组(P＜0.05或P＜0.01),总脂肪酸、不饱和脂肪酸(亚油酸、油酸、花生四烯酸、二十二碳六烯酸、花生三烯酸)、多不饱和脂肪酸(PUFA)和n6PUFA高于未合并代谢综合征组和正常组,差异有统计学意义(P＜0.05或P＜0.01).在研究对象中,脂联素与体重指数、腰围、腰臀比、甘油三酯呈负相关(r=-0.222,-0.235,-0.179,-0.194,P＜0.01或P＜0.05),与高密度脂蛋白胆固醇呈正相关(r=0.336,P＜0.01).总脂肪酸、多不饱和脂肪酸与体重指数、腰围、空腹血糖、平均血压呈正相关(r=0.241和0.280,0.198和0.188,0.226和0.298,0.274和0.334,P＜0.01或P＜0.05).结论 脂联素与游离脂肪酸代谢紊乱、n6系多不饱和脂肪酸升高,可能在原发性高血压合并代谢综合征的发病中起重要作用.     

妊娠糖尿病患者血游离脂肪酸与β细胞功能及胰岛素抵抗的关系

检测36例孕24～36周妊娠糖尿病患者和同期30例健康孕妇凌晨3:00、5:00及75 g葡萄糖负荷后血游离脂肪酸和胰岛素水平,比较两组胰岛素敏感性和胰岛素分泌功能.结果提示凌晨及糖负荷后高游离脂肪酸均与妊娠糖尿病患者胰岛素抵抗相关[胰岛素:(7.18±3.19)对(5.05±1.80)mIU/L(3:00)、(8.19±4.42)对(5.31±1.82)mIU/L(5:00)、(59.18±30.85)对(40.52±15.07)mIU/L(糖负荷后);游离脂肪酸:(0.39±0.20)对(0.23±0.11)mmol/L(3:00)、(0.46±0.17)对(0.29±0.12)mmol/L(5:00)、(0.19±0.13)对(0.09±0.06)mmol/L(糖负荷后);均P<0.01],糖负荷后30 min(早期相)的高水平的游离脂肪酸可能与妊娠糖尿病患者早期胰岛素分泌功能缺陷有关.     

血清脂肪因子与代谢综合征的关系

121例代谢综合征(MS)患者和120名对照者入选本研究以探讨血清脂肪因子与MS的关系.对照组、非腹型肥胖MS组及腹型肥胖MS组的血清抵抗素和脂肪细胞型脂肪酸结合蛋白(A-FABP)依次增高,而脂联素水平依次降低(均P<0.05).MS组抵抗素与体重指数(BMI)、腰围、收缩压、空腹血糖和A-FABP呈正相关(P<0.05或P<0.01);脂联素与高密度脂蛋白胆固醇呈正相关,而与BMI、腰围、空腹胰岛素、甘油三酯、稳态模型评估的胰岛素抵抗指数(HOMA-IR)呈负相关.     

急性冠脉综合征患者负荷后两小时血糖与冠状动脉病变程度的相关性研究

目的:研究急性冠脉综合征(ACS)患者负荷后2小时血糖和胰岛素抵抗与冠状动脉病变严重程度的关系.方法:入选88例ACS患者,男性60例,女性28例,均行冠状动脉造影检查.病情平稳后行75 g葡萄糖负荷试验和胰岛素释放试验,分为血糖正常组(n=28)、糖调节异常组(n=37)、糖尿病组(n:23),比较各组冠状动脉病变积分,并分析冠状动脉积分与负荷后2小时血糖水平、胰岛素抵抗的相关性.结果:①血糖正常组、糖调节异常组和糖尿病组冠状动脉积分,差异有统计学意义(P<0.01).与血糖正常组比,糖调节异常组和糖尿病组空腹胰岛素水平均升高(P<0.01).②88例患者冠状动脉积分与负荷后2小时血糖呈正相关(r=0.486,P<0.01),与空腹血糖呈正相关(r=0.308,P<0.01).冠状动脉积分与胰岛素抵抗指数呈正相关(r=0.217,P<0.05).多元线性回归分析显示负荷后2小时血糖和负荷后2小时胰岛素水平与冠状动脉积分呈正相关(偏相关系数分别为1.392,0.073,P<0.01).结论:ACS患者负荷后2小时血糖与ACS患者冠状动脉粥样硬化程度有关,餐后血糖越高冠状动脉损害越明显,胰岛素抵抗是其共同的基础.     

空腹甘油三酯正常的2型糖尿病患者餐后血脂的动态变化

目的探讨空腹甘油三酯正常的2型糖尿病患者脂肪餐后血脂水平的动态变化。方法通过脂肪餐负荷试验对25例空腹甘油三酯正常的2型糖尿病患者和20例健康对照者进行餐后血脂代谢的研究。分别于餐前、餐后2、4、6和8h用酶法测定总胆固醇和甘油三酯,一步法测定高低密度脂蛋白,葡萄糖氧化酶法测定血糖,化学发光免疫分析法测定免疫反应胰岛素,计算曲线下甘油三酯面积和增加面积。结果两组餐后甘油三酯平均值都有所升高,峰值在餐后4h。但糖尿病组餐后8h甘油三酯仍明显高于空腹水平(P<0.05),而对照组在餐后8h甘油三酯已恢复接近空腹水平(P>0.05)。两组的高密度脂蛋白在餐后4h都有一个轻微的低谷出现,但无组间差异(P>0.05)。总胆固醇和低密度脂蛋白在餐后无明显变化。两组曲线下甘油三酯面积和增加面积与餐后4h血清甘油三酯水平的相关性最显著(P<0.05)。结论2型糖尿病患者餐后脂代谢异常发生在空腹血脂异常之前。有必要联合检测空腹与餐后4h的甘油三酯水平来全面反映甘油三酯代谢是否存在异常。     

游离脂肪酸在高血压伴代谢综合征发病机制中的作用探讨

目的了解血清游离脂肪酸(FFA)在高血压伴代谢综合征(MS)发病机制中的作用。方法选取高血压伴MS、单纯高血压、健康人群各50例。检测所有对象的FFA、体重指数(BMI)、腰臀比(WHR)和外周胰岛素敏感度(SI)等指标。结果①MS高血压病组的血清FFA高于单纯高血压组及健康对照组(P<0.05)。②血清FFA与SI呈负相关(r=-0.785,P<0.05),与BMI、WHR、收缩压(SBP)呈正相关(r分别为0.801、0.856,P<0.05)。结论高血压伴MS患者的高血清FFA与胰岛素抵抗并存,并有可能是引起高血压伴MS患者其他病理生理改变的主要机制。     

新诊断2型糖尿病患者合并非酒精性脂肪肝临床分析

目的 探讨新诊断2型糖尿病(T2DM)患者发生非酒精性脂肪性肝病(NAFLD)的危险因素、临床特点.方法 对山西医科大学第一附属医院139例新诊断T2DM的住院患者进行回顾性分析,其中舍并NAFLD者65例,不合并NAFLD者74例.结果 2型糖尿病合并脂肪肝组与无脂肪肝组比较,体重指数(BMI)、三酰甘油(TG),高密度脂蛋白胆固醇(HDL-C)、空腹C肽(FCP)、餐后2 h C肽(2 h CP)、空腹胰岛素(FINS)、丙氨酸转氨酶(ALT)、胰岛素抵抗指数(HOMA-IR)以及24 h尿白蛋白(24 hUALB)有统计学意义(P<0.05或P<0.01);肥胖症、脂代谢紊乱、代谢综合征以及糖尿病肾病的发生率也明显增高(P<0.05或P<0.01);经Logistic回归分析,BMI、FCP和FINS是2型糖尿病并发脂肪肝的危险因素.结论 肥胖、胰岛素抵抗及脂质代谢紊乱是2型糖尿病并发脂肪肝的主要危险因素.     

糖尿病性心肌病变患者胰岛素强化治疗前后氧化应激水平的变化

目的:评价糖尿病性心肌病(DCM)患者胰岛素泵强化治疗前后氧化应激水平的变化。方法: 30例DCM患者采用胰岛素泵强化治疗,治疗达标前后进行超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、丙二醛（MDA）水平测定并进行比较。结果: 胰岛素泵强化治疗后,患者血浆中的SOD、GSH-PX水平明显上升（P<0.01）、MDA水平明显下降（P<0.01）。空腹血糖、餐后2 h血糖、胰岛素抵抗指数、总胆固醇、三酰甘油、低密度脂蛋白、游离脂肪酸明显降低（P<0.05）,胰岛素分泌功能指数明显上升（P<0.05）。结论: DCM患者使用胰岛素泵强化治疗后氧化应激水平明显降低。     

游离脂肪酸与代谢综合征合并冠心病的研究

目的探讨代谢综合征患者血清游离脂肪酸水平与冠心病的关系。方法选择54例单纯代谢综合征患者、57例代谢综合征合并冠心病患者和30例正常人,测定其血清游离脂肪酸水平并进行分析研究。结果代谢综合征患者的血清游离脂肪酸水平显著高于正常对照组;而代谢综合征合并有冠心病的患者血清游离脂肪酸水平显著高于单纯代谢综合征的患者。同时血清游离脂肪酸水平与血清胰岛素抵抗之间存在相关。结论血清游离脂肪酸可能是代谢综合征患者发展为冠心病的一个危险因子。     

Abnormalities of coagulation, platelet function, and fibrinolysis associated with syndromes of insulin resistance

Insulin resistance that accompanies obesity, hypertension, polycystic ovary syndrome, and the early phases of type 2 diabetes is characterized by a prothrombotic state. The prothrombotic state is a reflection of the direct effects of hyperinsulinemia and associated metabolic abnormalities (postprandial hyperglycemia, increased free fatty acids, and hypertriglyceridemia) on platelets, coagulation, and fibrinolysis. Therapies that improve insulin sensitivity and thereby decrease insulin resistance, hyperinsulinemia, and metabolic abnormalities decrease the prothrombotic state.     

Olive oil consumption and non-alcoholic fatty liver disease

The clinical implications of non-alcoholic fatty liver diseases （NAFLD） derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride （TG） accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon- like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include： decreased nuclear factor-kappa B activation, decreased low- density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines （tumor necrosis factor, interleukin-6） and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.     

Postprandial plasma adiponectin response is reduced in prepubertal premature pubarche girls

The association between premature pubarche (PP) and metabolic syndrome is controversial and not supported by some authors. The aim of this study was to determine insulin resistance syndrome, plasma adiponectin, and fatty acid profile in PP girls to discern potential confounder variables and markers of metabolic disturbances. We studied 22 prepubertal girls with a diagnosis of PP and 20 healthy controls who differed in body mass index (BMI) (19.33 ± 0.71 vs 17.30 ± 0.60). We evaluated insulin resistance syndrome components and postprandial response of adiponectin, nonesterified fatty acids, and fatty acid profile after consumption of a standardized breakfast. No lipid disturbances were detected in the PP group. High-density lipoprotein to low-density lipoprotein cholesterol ratio tended to be lower in PP girls (P = .052), but this effect disappeared when data were adjusted for both BMI and age (P = .480). Insulin levels tended to be higher at 2 hours in PP girls, who showed significantly higher C-peptide area under the curve. In contrast, adiponectin at 3 hours after the meal and postprandial adiponectin area under the curve were significantly lower. The PP girls showed significantly higher percentages of eicosapentaenoic acid in total plasma and plasma phospholipids. No differences were found in the postprandial fatty acid clearance rate. In conclusion, PP girls and controls differed in postprandial plasma adiponectin response and in postprandial plasma C-peptide response after both BMI and age adjustment. Cholesterol plasma disturbances were mainly attributable to their higher BMI, although n-3 polyunsaturated fatty acids were higher because of the PP.     

Non-alcoholic fatty liver disease and obesity: Biochemical,metabolic and clinical presentations

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m². However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m²) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.     

Effect of orlistat on postprandial lipemia, NMR lipoprotein subclass profiles and particle size

Evidence suggests that metabolic phenomena during postprandial lipemia may be important in the pathogenesis of atherosclerosis. Both lipid concentrations and lipoprotein subclass patterns may be important cardiovascular risk modifiers. The pancreatic lipase inhibitor orlistat reduces fat absorption by 30% and is used for the treatment of overweight and obesity. We evaluated the effect of orlistat on postprandial lipemia and lipoprotein particle distribution after moderate-and high-fat meals in healthy volunteers. In this double-blind, randomized, cross-over study, 10 healthy young men received orlistat 120 mg plus a high-fat meal (HFO), orlistat plus a moderate-fat meal (MFO) or placebo plus a high-fat meal (HFP). Plasma triacylglycerol, glucose, insulin, and free fatty acids were measured at baseline (fasting) and postprandially for 8h. Lipoprotein subclass profile was assessed by nuclear magnetic resonance spectroscopy. The 8h postprandial mean triacylglycerol area under the curve (AUC) was significantly lower with MFO and HFO (0.79 versus 1.33 mmol/lh) versus HFP (4.33 mmol/lh; p=0.02). Mean change in large VLDL subclass concentration during the 4-8h and mean VLDL size after 8h was significantly lower with HFO and MFO versus HFP (p<0.001). Small HDL particle concentration decreased significantly with HFP versus MFO or HFO (p<0.001). There was no significant difference in postprandial concentrations of glucose, insulin or free fatty acids on the different regimens. The lowering of postprandial triacylglycerol AUC, shorter postprandial lipemia, lower concentration of large triacylglycerol-rich particles and decrease of VLDL particle size supports the hypothesis of a less atherogenic postprandial lipoprotein profile following orlistat ingestion.     

Visfatin与代谢综合征的研究进展

Visfatin是新近发现的一种脂肪细胞因子，通过与胰岛素受体结合激活胰岛素信号转导通路，具有类胰岛素样作用。它的分泌受体内多种因素的调节，如激素、游离脂肪酸、葡萄糖。在代谢综合征相关疾病的发生发展过程中起重要作用，但目前对visfatin的研究存在很大争议，其作用机制有待于进一步探讨。     

Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus

Type 2 diabetes is associated with excessive food intake and a sedentary lifestyle. Local inflammation of white adipose tissue induces cytokine-mediated insulin resistance of adipocytes. This results in enhanced lipolysis within these cells. The fatty acids that are released into the cytosol can be removed by mitochondrial β-oxidation. The flux through this pathway is normally limited by the rate of ADP supply, which in turn is determined by the metabolic activity of the adipocyte. It is expected that the latter does not adapt to an increased rate of lipolysis. We propose that elevated fatty acid concentrations in the cytosol of adipocytes induce mitochondrial uncoupling and thereby allow mitochondria to remove much larger amounts of fatty acids. By this, release of fatty acids out of adipocytes into the circulation is prevented. When the rate of fatty acid release into the cytosol exceeds the β-oxidation capacity, cytosolic fatty acid concentrations increase and induce mitochondrial toxicity. This results in a decrease in β-oxidation capacity and the entry of fatty acids into the circulation. Unless these released fatty acids are removed by mitochondrial oxidation in active muscles, these fatty acids result in ectopic triacylglycerol deposits, induction of insulin resistance, beta cell damage and diabetes. Thiazolidinediones improve mitochondrial function within adipocytes and may in this way alleviate the burden imposed by the excessive fat accumulation associated with the metabolic syndrome. Thus, the number and activity of mitochondria within adipocytes contribute to the threshold at which fatty acids are released into the circulation, leading to insulin resistance and type 2 diabetes.     

The postprandial response of adiponectin to a high-fat meal in normal and insulin-resistant subjects

OBJECTIVE: Adiponectin is an adipose-specific protein with short-term effects in vivo on glucose and fatty acid levels. We studied the plasma concentration and the proteolytic activation status of adiponectin following the consumption of a high-fat, low-carbohydrate meal. DESIGN: Analysis of adiponectin concentration and polypeptide structure after consumption of a fat meal. SUBJECTS: Normal subjects (n=24) and first-degree relatives of patients with type II diabetes (n=20). MEASUREMENTS: All subjects had a normal fasting plasma glucose and glucose tolerance. Blood was collected for the determination of plasma insulin, adiponectin, triglyceride, and free fatty acids. Body composition was assessed with dual-energy X-ray absorptiometry and whole-body insulin sensitivity with a euglycaemic, hyperinsulinaemic clamp. Postprandial response over 6 h was determined for plasma adiponectin, glucose, insulin, triglyceride, and free fatty acids. Adiponectin was measured by commercial RIA and its polypeptide structure examined by Western blotting. RESULTS: The relatives were more insulin resistant and had increased adiposity compared with control subjects. There was no significant difference in postprandial response in fatty acids, triglyceride, or insulin between the groups. Postprandial levels of adiponectin measured by radioimmunoassay were not significantly different from fasting levels, and no breakdown products of adiponectin were detectable in postprandial samples by Western blotting. CONCLUSIONS: Levels of circulating adiponectin do not alter in response to a fat meal, despite evidence in mice that acute changes in adiponectin significantly affect postprandial fatty acid flux. Moreover, a fat meal challenge did not lead to significant activation of adiponectin by proteolytic conversion.     

Carbohydrate and lipid metabolism during human labor: Free fatty acids,glucose, insulin,and lactic acid metabolism during normal and oxytocin-induced labor for postmaturity

This investigation was performed to study the metabolism of the major body fuels (viz. glucose and free fatty acids), insulin, and lactic acid during the stress of human labor. In addition, the role of the normal placenta in the transport of these substances between mother and the fetus was evaluated by measuring them in the mother and cord blood at delivery. To study possible alterations of this role in the placenta which had exceeded the normal period of gestation, a second comparable group of women had labor induced with oxytocin 16–18 days beyond the expected date of delivery. A dramatic twofold increase in maternal plasma free fatty acids was observed during labor. There was a lesser but definite increase in blood glucose concentrations. No rise in serum insulin levels was noted which coincided with the changes in blood glucose. Lactic acid concentrations during the course of labor were variable from baseline but at delivery, the concentrations rose to very significant levels. Free fatty acids and blood glucose levels were significantly higher in the maternal than in the fetal side. A significantly positive correlation was noted between the maternal and cord blood values except for free fatty acids in the postmature group. No significant difference, nor a correlation was found between the two compartments in the insulin nor lactic acid levels.These results suggest that during human labor free fatty acids are the principal metabolic fuel. This increase in maternal free fatty acids may serve to spare glucose as a metabolic fuel in the fetus. The mechanism responsible for the increase maternal free fatty acid mobilization remains to be determined. It is not possible to discern any consistant alteration in placental function as a consequence of prolonged gestation.