游离脂肪酸及高糖对内皮细胞功能的影响研究

目的 探讨游离脂肪酸及高糖对人脐静脉内皮细胞(HUVECs)的功能的影响及可能机制.方法 研究游离脂肪酸及高糖对血管内皮细胞功能指标一氧化氮(NO)和可溶性细胞间黏附分子-1(sICAM-1)的影响;用激光共聚焦显微镜观察游离脂肪酸及高糖对PKCα、PKCδ的影响.结果 不同浓度游离脂肪酸及高糖均可诱导内皮细胞功能紊乱及PKCα及PKCδ表达位置转移及表达增强,高糖中加入游离脂肪酸可使变化更显著.结论 游离脂肪酸及高糖均可导致内皮细胞功能紊乱,可能部分是通过PKCα及PKCδ途径来实现的.     

实验性大鼠急性胰腺炎严重程度与血清多种游离脂肪酸相关性研究

目的通过探讨多种血清游离脂肪酸与急性胰腺炎严重程度以及炎性因子关系,探讨游离脂肪酸在重症急性胰腺炎(SAP)发病中的作用,寻找不同游离脂肪酸类型与急性胰腺炎的关系.     

代谢综合征患者脂肪餐负荷对血甘油三酯、血糖和血胰岛素的影响

采用脂肪餐耐量试验观察代谢综合征患者餐后甘油三酯和游离脂肪酸的变化,探讨两者与胰岛素抵抗等的关系.发现代谢综合征患者空腹及餐后血脂代谢均存在异常(P<0.05或P<0.01).尤以餐后脂代谢异常更显著(P<0.05或P<0.01),其因为可能是胰岛素对游离脂肪酸的抑制作用减弱,使餐后游离脂肪酸明显增高而且清除延迟.     

心房颤动患者血清高敏C反应蛋白与游离脂肪酸的变化

目的 探讨高敏C反应蛋白、游离脂肪酸在心房颤动(房颤)发病中的意义.方法 测定41例持续性房颤患者(持续性房颤组)、42例阵发性房颤患者(阵发性发颤组)以及39例健康体检者(正常对照组)血清中高敏C反应蛋白及游离脂肪酸水平.结果 血清高敏C反应蛋白及游离脂肪酸水平在持续性房颤组、阵发性房颤组均显著高于对照组(P＜0.01),且持续性房颤组高于阵发性房颤组(P＜0.01),各组间差异均有统计学意义.结论 高敏C反应蛋白及游离脂肪酸增高所反映的炎症状态和代谢紊乱可能促进房颤的发生发展.     

游离脂肪酸对βTc6细胞PDX-1表达及胰岛素分泌能力的影响

目的 探讨游离脂肪酸对胰岛β细胞胰-十二指肠同源盒因子-1(PDX-1)的表达及相应的β细胞增殖活性和胰岛素分泌功能变化的影响.方法 0.25～1.00 mmol/L游离脂肪酸干预小鼠胰岛素瘤细胞系βTc6细胞24～48 h,应用RT-PCR法检测转录因子PDX-1 mRNA表达,四甲基偶氮唑盐法检测细胞的增殖活性,放射免疫法检测葡萄糖刺激的胰岛素分泌水平,并观察细胞形态变化.结果 经0.25～1.00 mmol/L游离脂肪酸干预24 h,βTc6细胞PDX-1 mRNA的转录逐步增加,但随着干预时间进一步延长至48 h,PDX-1 mRNA的转录逐渐回落,特别是用1.00 mmoL/L游离脂肪酸干预48 h后,βTc6细胞PDX-1 mRNA的表达低于空白对照组.经过0.50～1.00 mmol/L游离脂肪酸24～48 h的干预之后,βTc6细胞形态学上呈现凋亡趋势,细胞增殖活力以及葡萄糖刺激的胰岛素分泌功能降低,而0.25 mmol/L游离脂肪酸24 h的干预未见此类现象.结论 短时间低浓度的游离脂肪酸干预可介导β细胞转录因子PDX-1的表达上调,对β细胞的增殖活性和胰岛素分泌能力无明显影响;而长时间高浓度的游离脂肪酸干预则将导致PDX-1 mRNA的表达下调,并使β细胞的增殖活性和胰岛素分泌能力受损.     

脂毒性与胰岛素抵抗的相关研究进展

胰岛素抵抗是2型糖尿病发病的环节之一,与血浆中游离脂肪酸水平的变化密切相关.血循环中游离脂肪酸升高,可在多个层面影响葡萄糖代谢,使胰岛素作用的靶组织如肝脏、肌肉和脂肪组织表现为胰岛素抵抗.本文将就这方面的研究做一个简要综述.     

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。     

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。     

以游离脂肪酸为结合配体的GPCRs的研究进展

食物营养成分在肠道中可被分解产生游离脂肪酸.游离脂肪酸除了被吸收氧化分解产生能量供机体利用外,还能通过结合脂肪酸受体激活信号通路,参与多种生理功能的调节,如维持能量平衡、代谢稳态、调节脂质形成与分解、影响机体免疫、结识流动消化成分间接监测菌群数量等.被确认的游离脂肪酸受体包括结合长链脂肪酸的G蛋白偶联受体(GPR)12...     

游离脂肪酸与胰岛素抵抗

近年来认为游离脂肪酸在肥胖和2型糖尿病中发挥着重要作用。本文综述了游离脂肪酸与糖代谢的关系及胰岛素抵抗的产生机制、胰岛素抵抗的相关因子及降低游离脂肪酸途径的新进展。     

2型糖尿病血小板活化物质表达与脑梗死的关系

目的　探讨 2型糖尿病患者血小板活化物质表达与脑梗死的关系。　 方法 　采用流式细胞仪对 76例 2型糖尿病和 3 2例糖耐量减退患者测定血小板活化、血小板与白细胞粘附的表达。　 结果　无论 2型糖尿病组还是糖耐量减退组发生急性脑梗死患者血小板活化、血小板与白细胞粘附水平高于腔隙性脑梗死患者 (P <0 0 5 ) ,后者又高于未发生脑梗死患者 (P <0 0 5 ) ;2组中发生急性脑梗死和腔隙性脑梗死患者血小板活化、血小板与白细胞粘附水平与对照组比较差异有显著性 (P <0 0 5 )。　 结论 　 2型糖尿病和糖耐量减退患者测定血小板活化、血小板与白细胞粘附表达对缺血性脑卒中的早期诊断和病情监测有一定的临床价值     

Relation of alcohol use and smoking to glucose tolerance status in Japanese men

To investigate the relation of alcohol use and cigarette smoking to glucose tolerance status, we performed a cross-sectional study of 3038 male officials aged 46-59 years in the Self-Defense Forces. Glucose tolerance status was determined by a 75-g oral glucose tolerance test. A self-administered questionnaire was used to ascertain alcohol use, smoking habits, and other lifestyle characteristics. Statistical adjustment was made for parental history of diabetes, body mass index, and leisure-time physical activity. Alcohol use was positively associated with impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes mellitus each. The association was dose-dependent, with odds of each category of glucose intolerance increased even among those with moderate alcohol use. Cigarette smoking was not related to any categories of glucose intolerance. Alcohol use may confer increased risks not only of type 2 diabetes mellitus but also of preceding glucose intolerance status. Smoking does not seem to deteriorate glucose tolerance.     

Lifestyle intervention, glucose tolerance, and risk of developing type 2 diabetes mellitus

Diabetes mellitus is rapidly becoming one of the main health issues in the 21st century. Environmental factors such as lifestyle habits (i.e., physical inactivity and dietary intake) and obesity may act as initiating factors or progression factors for type 2 diabetes. Therefore, changes in lifestyle (i.e., diet and physical activity) should have the potential to postpone or prevent the development of type 2 diabetes mellitus in subjects at high risk (for example, those with impaired glucose tolerance [IGT]). Several independent and well-controlled randomized studies have shown the beneficial impact of a lifestyle intervention program on glucose tolerance, insulin resistance, and diabetes risk in populations at risk for developing type 2 diabetes mellitus. After 2 years of a combined diet and physical activity intervention program, according to general public health guidelines, the Study on Lifestyle-intervention and IGT Maastricht (SLIM) revealed an improved glucose tolerance in the intervention group compared to a further deterioration in the control group. The Finnish Diabetes Prevention Study (DPS) and the US Diabetes Prevention Program (DPP) both observed a 58% reduction in diabetes risk after 3 years of intervention in a high-risk population. Although other intervention strategies can reduce the incidence of diabetes, lifestyle changes are the most effective mean of delaying or preventing the development of type 2 diabetes mellitus. For a successful implementation of a diabetes prevention program in a primary healthcare setting, both patients and healthcare professionals should be aware of the (clinical) significance of impaired glucose tolerance and the effectiveness of lifestyle interventions to prevent or postpone type 2 diabetes mellitus and its complications.     

Nicht entdeckte Glukosestoffwechselstörungen bei koronarer Herzkrankheit

The numbers affected by diabetes mellitus type 2 have increased throughout the world in recent years, and it is assumed that there is also a high number of undiagnosed cases. A study in southern Germany showed that half of all cases of diabetes in the elderly general population were undiagnosed. Both type 2 diabetes mellitus and impaired glucose tolerance are among the main risk factors for coronary artery disease, which accounts for most of the high morbidity and mortality in this group of patients. The prevalence of hitherto unknown glucose metabolism disorder is far higher in patients with acute myocardial infarction than in the general population. Furthermore, a recent study showed that two-thirds of patients with stable coronary artery disease had undiagnosed diabetes mellitus or impaired glucose tolerance. An oral glucose tolerance test is crucial to the diagnosis: the glucose metobolism disorder would have remained undetected in two-thirds of diabetic patients if only fasting blood glucose had been measured. In view of these high prevalence rates an oral glucose tolerance test should be considered in all patients with coronary artery disease to exclude any disorder of glucose metabolism.     

Pathophysiology of prediabetes

The term prediabetes refers to subjects with impaired fasting glucose and/or impaired glucose tolerance who are at increased risk for type 2 diabetes mellitus. Although both types of patients are at increased risk for developing type 2 diabetes mellitus and cardiovascular disease, they manifest distinct metabolic abnormalities. In this article, we summarize the metabolic abnormalities that characterize each state and the contribution of these metabolic abnormalities to the increased risk of diabetes and cardiovascular disease.     

Diabetes mellitus or an impaired glucose tolerance as a potential complicating factor in patients treated with high-dose therapy and autologous bone marrow transplantation

We asked in a retrospective analysis whether patients with diabetes mellitus or impaired glucose tolerance are at increased risk for morbidity and mortality after high-dose therapy followed by an autologous bone marrow transplantation. Nine patients with diabetes mellitus (n = 7) or impaired glucose tolerance (n = 2) were identified who had been treated with high-dose therapy and autologous bone marrow transplant for lymphoid malignancies. At the start of the pretransplant conditioning all patients had a Karnofsky score of at least 80 and no clinically demonstrable organ dysfunction. One patient with diabetes mellitus type I (DM I) was transplanted without any complications. The patients with diabetes mellitus type II (DM II) or an impaired glucose tolerance had complications of life-threatening infections (in 6/8), acute renal insufficiency (in 3/8), liver abnormalities with elevated liver enzymes or liver failure (in 4/8) and congestive heart failure (in 1/8). Although the complications observed are not infrequent in the transplant setting, because of the good performance status before BMT and the absence of clinically demonstrable organ impairment before transplantation, it is our impression that the presence of diabetes mellitus or glucose intolerance might be an important co-factor in the morbidity of these patients.     

Prevention of T2DM in women with a previous history of GDM

Women with a history of gestational diabetes mellitus (GDM) have a high risk of progression to type 2 diabetes mellitus (T2DM). Risk factors are similar for GDM and T2DM and include, among others, obesity, family history, and ethnic background. GDM is also associated with the metabolic syndrome. Women with impaired glucose tolerance or "prediabetes" postpartum have the highest risk of progression. In women with impaired glucose tolerance, lifestyle modification or pharmacologic therapy may prevent or delay the onset of T2DM.     

Epidemiology of the diabetic heart

Diabetes mellitus is a worldwide epidemic. Cardiovascular disease remains the major cause of morbidity and mortality in people with diabetes. Studies have suggested that increased risk of cardiovascular disease is not restricted to type II or type I diabetes mellitus, but extends to prediabetic stages such as impaired fasting glucose, impaired glucose tolerance, metabolic syndrome, and obesity. Insulin resistance, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus form a continuous sequence of risk for cardiovascular disease. Therefore, cardiovascular disease mortality and morbidity within the diabetes epidemic grow into vast proportions. Evidence also exists that diabetic patients have a high prevalence of heart failure or impaired diastolic and systolic cardiac function subsequent to the combination of coronary artery disease, hypertension, and diabetic cardiomyopathy. In view of the proportions of this new epidemic, prevention of diabetes and its prediabetic states is likely to be the most effective strategy to prevent serious cardiovascular events.     

Coincident diabetes mellitus and primary hyperparathyroidism

The prevalence of diabetes mellitus in primary hyperparathyroidism is ～8% and that of primary hyperparathyroidism in diabetic patients is ～1%. Both values are about three‐fold higher than the respective expected prevalences in general populations. Patients with both disorders are over 40 years of age and80% are female; 22% have type 1 and 78% type 2 diabetes. Primary hyperparathyroidism presents first in ～20% of patients, and diabetes mellitus in 40%; both disorders present together, or within 1 year, in 40%. Approximately 40% of patients with primary hyperparathyroidism have impaired glucose tolerance. Insulin resistance is present in hyperparathyroidism and probably arises from a raised intracellular free calcium concentration which, by decreasing normal insulin‐stimulated glucose transport, increases the requirement for insulin: if this insulin resistance progresses, impaired glucose tolerance and diabetes mellitus would result. Parathyroidectomy has been followed by regression of diabetes and of impaired glucose tolerance in some but not all patients. Early diagnosis of the second disorder is clinically desirable when one disorder is present. Hyperparathyroid patients should therefore be screened for impaired glucose tolerance and diabetes annually, and pre‐operatively. Diabetic patients should be checked for hypercalcaemia at appropriate intervals; although only 1% of them may have hyperparathyroidism, this disorder if untreated is associated with hypertension, to which diabetic patients are already prone. Copyright © 2001 John Wiley & Sons, Ltd.     

HbA1c as predictor of all-cause mortality in individuals at high risk of diabetes with normal glucose tolerance, identified by screening: a follow-up study of the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION), Denmark

Aims/hypothesis  

Stepwise screening for type 2 diabetes will not only identify people with the disease or some other form of dysglycaemia (impaired fasting glucose or impaired glucose tolerance), but also many individuals who are phenotypically at high risk of developing diabetes, but currently have normal glucose tolerance (NGT). We therefore sought to assess whether HbA_1c adds prognostic information in relation to all-cause mortality in people who have NGT and a high risk of type 2 diabetes mellitus.