Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients

The main aim of the present study was to investigate the plasma phospholipids (PL) fatty acids status and its association with plasma Hcy in patients with type 2 diabetes mellitus (T2DM). One hundred and four T2DM (aged 57.3±13.4 y) and 150 healthy subjects (aged 48.4±8.7 y) were recruited. Plasma Hcy and PL fatty acids were determined by standard methods. Plasma Hcy concentration in T2DM was significantly higher than that in healthy subjects (p<0.001). The prevalence of hyperhomocysteinemia was significantly higher in T2DM (36.54%) than that in healthy subjects (17.32%) (p=0.012). Plasma PL 20:4n-6 (r=0.303, p=0.012), 22:5n-3 (r=0.312, p=0.01), total PUFA (r=0.303, p=0.012), n-6 PUFA (r=0.261, p=0.032) were significantly positively associated with plasma Hcy concentration in T2DM. While, plasma PL n-3:n-6 PUFA (r=-0.400, p=0.046) was negatively associated with plasma Hcy in T2DM. In healthy subjects, plasma PL 22:6n-3 (r=-0.201, p=0.042) was negatively associated with plasma Hcy. In addition, plasma PL 22:6n-3 (r=0.193, p=0.044) and 22:5n-6 (r=0.234, p=0.038) were significantly negatively associated with plasma vitamin B-12 in healthy subjects. Our results suggested that increased plasma Hcy levels in T2DM associated with low n-3:n-6 ratio intake. We suggest that T2DM increase their long chain n-3 PUFA intake from fish or fish oil while decrease n-6 PUFA intake.     

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus. Effect of omega-3 fatty acids

In a previous study, we showed that prior oral feeding of oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure omega-6 fatty acids gamma-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with omega-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. alpha-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that omega-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.     

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: effect of omega-6 fatty acids

OBJECTIVE: We previously showed that prior oral supplementation of oils rich in omega-3, eicosapentaenoic acid and docosahexaenoic acid, and omega-6, gamma-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with omega-6 fatty acids. METHODS: Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, gamma-linolenic acid, and arachidonic acid (AA) but not to dihomo-gamma-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with gamma-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. RESULTS: Even though pretreatment with linoleic acid and dihomo-gamma-linolenic acid and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. gamma-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. CONCLUSIONS: These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.     

n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review

Historically, epidemiologic studies have reported a lower prevalence of impaired glucose tolerance and type 2 diabetes in populations consuming large amounts of the n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) found mainly in fish. Controlled clinical studies have shown that consumption of n-3 LC-PUFAs has cardioprotective effects in persons with type 2 diabetes without adverse effects on glucose control and insulin activity. Benefits include lower risk of primary cardiac arrest; reduced cardiovascular mortality, particularly sudden cardiac death; reduced triglyceride levels; increased high-density lipoprotein levels; improved endothelial function; reduced platelet aggregability; and lower blood pressure. These favorable effects outweigh the modest increase in low-density lipoprotein levels that may result from increased n-3 LC-PUFA intake. Preliminary evidence suggests increased consumption of n-3 LC-PUFAs with reduced intake of saturated fat may reduce the risk of conversion from impaired glucose tolerance to type 2 diabetes in overweight persons. Reported improvements in hemostasis, slower progression of artery narrowing, albuminuria, subclinical inflammation, oxidative stress, and obesity require additional confirmation. Expected health benefits and public health implications of consuming 1 to 2 g/day n-3 LC-PUFA as part of lifestyle modification in insulin resistance and type 2 diabetes are discussed.     

Prevention of chemically induced diabetes mellitus in experimental animals by polyunsaturated fatty acids

Previous studies showed that essential fatty-acid deficiency, conjugated linoleic acid, and a peroxisome proliferator-activated receptor-gamma binding agent such as troglitazone can prevent the development of diabetes mellitus in experimental animals. In the present study, we observed that oral supplementation with oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid could protect the animals against alloxan-induced diabetes mellitus. These oils rich in omega-3 and omega-6 fatty acids not only significantly attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range. Changes in the concentrations of different fatty acids shown by the phospholipid fractions of plasma, liver, and muscle tissues that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in these animals. Based on these results and the known mechanisms of alloxan, we suggest that omega-3 and omega-6 long-chain fatty acids can prevent chemically induced diabetes mellitus by enhancing the antioxidant status and suppressing production of cytokines.     

Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus

Insulin resistance is defined as the reduced responsiveness to normal circulating levels of insulin. It is the basic condition of type 2 diabetes mellitus, in which both experimental animals and humans accumulate lipids intracellularly in skeletal muscle and liver. Measurement of these lipids in humans, using nuclear magnetic resonance spectroscopy after lipid infusion, indicated they could cause inhibition of the glucose transporter GLUT4, thereby suppressing glucose entry into cells and inhibiting glucose oxidation and glycogen synthesis in muscle. Furthermore, it is known that the enzyme acetyl-CoA carboxylase2 (ACC2) suppresses the oxidation of fatty acids by inhibiting the entry of fatty acids into mitochondria. Further support for the lipocentric hypothesis of the pathogenesis of insulin resistance was provided by knocking out the gene coding for ACC2 in mice; this led to greater fatty acid oxidation, reduced fat mass and, in consequence, greatly enhanced insulin sensitivity. These studies suggest that a specific inhibitor of ACC2 would have therapeutic potential for type 2 diabetes mellitus.     

饮食、C反应蛋白与2型糖尿病颈动脉内膜厚度的关系

目的比较2型糖尿病颈动脉内膜增厚与未增厚患者的营养摄入特点及C反应蛋白（CRP）水平差异，分析饮食、CRP与颈动脉内膜厚度的关系。方法2007年2月至9月在广州市第一医院门诊或住院治疗的2型糖尿病患者60例，平均年龄（59．5±7．27）岁，根据颈动脉内膜是否增厚分为两组（n=30），进行膳食调查、人体测量，检测血高敏CRP、尿微量白蛋白、血糖、C肽、血脂、糖化血红蛋白、肾功能等指标，并比较两组结果。结果2型糖尿病颈动脉内膜未增厚组的日均蔬菜类、水果类、水产类和维生素C摄入量均明显高于颈动脉内膜增厚组（P〈0．05），颈动脉内膜增厚组的高敏CRP明显高于2型糖尿病颈动脉内膜未增厚组（P=0．000），两组其余实验室指标的差异均无统计学意义。2型糖尿病患者高敏CRP与颈动脉内膜厚度呈正相关（r=0．36，P=0．004）；血清CRP水平与蔬菜水果的摄入量呈负相关（r=-0．334，P=0．01），与水产类的摄入量呈负相关（r=-0．315，P=0．016），与膳食维生素C的摄入量呈负相关（r=-0．2786，P=0．038）；水果摄入量与内膜厚度呈负相关（0=-0．33，P=0．01）。结论膳食中蔬果类、水产类食物、维生素C可能是2型糖尿病动脉粥样硬化的保护因子，增加摄入可能有利于糖尿病患者预防动脉粥样硬化，CRP与2型糖尿病动脉粥样硬化的发生发展相关联。     

饮食、C反应蛋白与2型糖尿病颈动脉内膜厚度的关系

Objective To compare the characteristics of food and nutrition intake in type 2 diabetes mellitus (T2DM) patients with or without carotid atherosclerosis and analyze the relationship between diets/C-reactive protein (CRP) and carotid intima-media thickness (C-IMT). Methods Sixty patients with T2DM were enrolled and divided into two groups based on C-IMT: group A (C-IMT ＜ 1 mm, n=30) and group B (C-IMT≥1 mm, n=30). All subjects were investigated with questionnaires including 3-day food recall They all took somatometric measurement. Blood and urine samples were collected in all subjects to examine the levels of high sensitive-CRP,C-peptide, blood glucose, glycosylated hemoglobin, blood lipid, renal function, urine microalbumin, and other indicators. Results The intakes of vegetables, fruits, and aquatic products were significantly higher in group A than in group B ( P ＜ 0. 05 ). The intake of vitamin C in group A was significantly higher than that in group B ( P ＜0. 05 ). The levels of CRP in group B was significant higher than that in group A (P = 0. 000). Positive correlation was found between CRP level and C-IMT in T2DM patients ( r = 0. 36, P = 0. 004). Furthermore, CRP was negatively correlated with the intakes of vegetables and fruits ( r = - 0. 334, P = 0. 01 ), aquatic products ( r = -0. 315, P = 0. 016), and vitamin C ( r = - 0. 2786, P = 0. 038 ), respectively. The intake of fruits was negatively correlated with C-IMT (r, = -0. 33, P = 0. 01 ). Conclusions T2DM patients without carotid atherosclerosis intake more vegetables, fruits, aquatic products and vitamin C than those with atherosclerosis. Vegetables, fruits,sea foods and vitamin C may be the protective factors against atherosclerosis in T2DM patients. CRP is associated with the development of atherosclerosis in T2DM patients.     

孕中期血浆n-6多不饱和脂肪酸水平与妊娠期糖尿病的关联

目的  探讨中国西南地区孕妇孕中期血浆n-6多不饱和脂肪酸(polyunsaturated fatty acids, PUFAs)水平与妊娠期糖尿病(gestational diabetes mellitus, GDM)的关联。方法  本研究基于同济-双流出生队列,于2017-2019年在成都市双流区妇幼保健院围产保健门诊纳入18~40岁的6 143名单胎妊娠孕妇。通过问卷调查收集孕妇基本信息和孕期健康状况,并对其进行体格测量和血液样本收集。根据孕24~28周孕妇75 g口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)结果,选取269名符合GDM诊断标准的孕妇作为病例组。在非GDM的孕妇中按照孕妇年龄(±3岁)、基线孕周(±4周)进行1∶2匹配,选取538名非GDM孕妇作为对照组。采用气相色谱-质谱联用的方法检测孕妇孕中期血浆多种n-6 PUFAs水平。采用多变量校正的条件Logistic回归分析模型评估孕中期血浆各n-6 PUFAs类别和总n-6 PUFAs与GDM患病风险的关联,并利用错误发现率(false discovery rate, FDR)法校正多重检验。采用敏感性分析探讨其稳健性。结果  807名研究对象的年龄为(27.8±3.9)岁,孕周为(24.8±1.1)周,孕前BMI为(21.5±3.1) kg/m²。孕中期血浆亚油酸(linoleic acid, LA)、γ-亚油酸(gamma-linolenic acid, GLA)、二十碳二烯酸(eicosadienoic acid, EDA)和花生四烯酸(arachidonic acid, AA)水平每增加一个标准差,GDM的患病风险的OR值分别为0.83(95% CI：0.69~0.99, P=0.039)、0.82(95% CI：0.69~0.99, P=0.037)、0.63(95% CI：0.50~0.79, P < 0.001)和1.20(95% CI：1.02~1.42, P=0.032),而多重校正后LA、GLA和AA与GDM患病风险关联无统计学意义(均有P > 0.05)。敏感性分析结果显示EDA与GDM患病风险的关联稳定。结论  孕中期血浆n-6 PUFAs中EDA与GDM患病风险有关,此结论需进一步在大样本人群中进行验证。     

2型糖尿病患者血清超敏C-反应蛋白与尿微量白蛋白关系的探讨

目的研究尿微量白蛋白(mAlb)与血清超敏C-反应蛋白(hs-CRP)联合测定对2型糖尿病(T2DM)患者早期肾损伤的诊断价值。方法对60例2型糖尿病患者及60例健康体检者的尿微量白蛋白与血清超敏C-反应蛋白,采用日立7180型生化分析仪,使用志荣公司提供的尿微量白蛋白检测试剂盒及血清超敏C-反应蛋白检测试剂盒,应用免疫比浊法进行测定,并对两种指标的相关性进行分析。结果 2型糖尿病组超C-反应蛋白为(3.58±1.06)mg/L,尿微量白蛋白为(36.54±10.27)mg/L,与健康对照组相比均差异有统计学意义(P<0.05)。结论血清超C-反应蛋白和尿微量白蛋白的联合检测,可以有效提高对2型糖尿病肾病早期的检测率。     

Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes

BACKGROUND: Plasma lipoproteins may be classified by their apolipoprotein composition. The lipoprotein subclass containing apolipoproteins B and C (LpB:C) is considered the most atherogenic. OBJECTIVE: We evaluated the acute effects of individual fatty acids on apolipoprotein B (apo B)-containing lipoproteins in adults with type 2 diabetes (n = 15). DESIGN: We administered 3 meals in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA + 3.5 g alpha-linolenic acid (ALA; MUFA + ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA + EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB:C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow-mediated dilation was measured at baseline and 4 h after the meal. RESULTS: The treatments significantly increased apo B and LpB postprandially (P < 0.03 for both), but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA (treatment x time interaction, P < 0.0001). MUFA + ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols (>/=1.69 mmol/L) but was the only treatment to significantly increase this particle in those with low triacylglycerols (treatment x group interaction, P < 0.0001). Examination of change scores did not reveal the source of the interaction of treatment and time (P < 0.007) for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function. CONCLUSIONS: The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA + EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.     

2型糖尿病和葡萄糖耐量异常患者游离脂肪酸升高及其意义

目的　观察 2型糖尿病 (DM)和葡萄糖耐量异常 (IGT)患者血清游离脂肪酸 (FFA)的水平 ,探讨FFA与胰岛素(INS)、胰岛素抵抗 (IR)和甘油三酯 (TG)的关系。方法　采用酶法测定 2 0例 2型DM和 2 0例IGT患者口服葡萄糖耐量试验 (OGTT) 0和 2h血清FFA水平 ,同步测定血浆葡萄糖 (PG)、血清INS以及空腹TG和胆固醇 (TC) ,并与 2 0例正常人对照。结果　 2型DM和IGT患者OGTT 0和 2hINS均显著高于正常对照组 ,且 2型DM患者INS高于IGT患者 ,P <0 .0 5 ;空腹FFA和胰岛素抵抗指数 (HOMA -IR) 2型DM患者高于IGT患者 ,IGT患者高于正常对照组 ,P <0 .0 1;TG和OGTT 2hFFA 2型DM患者高于IGT患者和正常对照组 ,P <0 .0 5 ,而IGT患者和正常对照组之间比较差异无显著性 ;多元逐步回归显示空腹FFA是HOMA -IR的独立影响因素。结论　不仅 2型DM患者而且IGT患者存在FFA异常升高 ,FFA升高与IR有关 ;2型DM和IGT患者存在IR和脂代谢紊乱 ,FFA反映脂代谢紊乱可能较TG更灵敏的指标     

非酒精性脂肪性肝病与2型糖尿病的相关性

非酒精性脂肪性肝病(NAFLD)是一种近年来逐渐被广泛认识的慢性肝脏疾病,随着人们生活水平的提高和饮食结构的变化,NAFLD发病率在我国也明显上升.其发病与肥胖、脂代谢紊乱、胰岛素抵抗、糖尿病有关,是代谢综合征的肝脏表现[1].现就NAFLD和2型糖尿病的相关性进行简要介绍.     

Dynamic study of the changes in the composition of fatty acids in serum lipid fractions under a diet rich in polyunsaturated fatty acids

Appropriate adjustment of diet and specially reduction of the saturated fatty acids content is the cornerstone of correcting many hyperlipidemias. What we have tried in our study was first to show the evolution of the changes in the serum's fatty acids composition under a rich polyunsaturated fatty acids diet, second to find an index proving that the diet had correctly been taken. Chromatographic analysis were performed after ultracentrifugal separation of the lipoprotein fractions. Seven volunteers, non fat, and normolipemics were selected. Samples were collected every three or five days before and during the diet. The whole test lasted twenty days. What had been shown is that the linoleic acid content increased but the one of the oleic acid decreased in all lipoprotein fractions. Those changes are bestly illustrated by using the (formula: see text) ratio as a kinetic index. The triglycerid fraction modifications are faster than the phospholipid's one. Concerning the other fatty acids, the modifications are less spectacular : the palmitic acid decrease in every lipids fractions and the palmitoleic acid has a significant decrease only in the esterified cholesterol. And the stearic acid has no variation at least significatively.     

Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells

The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein.