Role of Isoflavones in the Hypocholesterolemic Effect of Soy

Epidemiologic data suggest an inverse relationship between the consumption of soy isoflavones and cardiovascular disease risk. The aims of this review are to determine if isoflavones play a role in the hypocholesterolemic effect of soy and whether the studies realized with that scope were adequately designed. In humans, most studies have been performed in postmenopausal women. The results are inconsistent, however; some studies show a decrease in total cholesterol and low-density lipoprotein concentrations, and an increase in high-density lipoprotein levels, and other investigations fail to show any beneficial effect of soy isoflavones on lipid profiles. In most studies, beneficial effects could not be attributed with certainty to soy isoflavones. If these components have any health-protecting effect in humans, it is small in comparison with the effect of soy protein itself. There are currently not enough data to recommend the consumption of isoflavone supplements to lower plasma cholesterol levels.     

The distribution profiles of very low density and low density lipoproteins in poorly-controlled male,Type 2 (non-insulin-dependent) diabetic patients

Summary The distribution and composition of lipoproteins spanning the very low density and low density lipoprotein spectra have been analysed in ten poorly-controlled, male, Type 2 (non-insulin-dependent), diabetic patients pre-disposed to mild, secondary hypertriglyceridaemia. As compared to age-matched control subjects, the diabetic patients displayed grossly modified, distinctly atherogenic lipoprotein profiles. Modifications were not limited to the very low density lipoprotein profile, as would be expected from the pre-treatment hypertriglyceridaemia. There was also an aberrant low density lipoprotein profile, which was not evident from plasma cholesterol measurements, especially as the diabetic patients at entry were well matched to control subjects with respect to plasma levels of this lipid. Compositional abnormalities were also observed in the poorly-controlled diabetic group, although these were less marked than the distributional changes. There were substantial improvements of the abnormalities detailed above, even over a short treatment period (two weeks), with therapy designed primarily to ameliorate metabolic control. The data suggest that, in the presence of poor metabolic control and hypertriglyceridaemia, occult, atherogenic modifications of low density lipoproteins can occur. The results argue in favour of strict control of triglyceride levels even in diabetic patients with apparently acceptable cholesterol levels.     

脂联素、直接胆红素及甘油三酯对2型糖尿病患者大血管病变的诊断价值

目的 探讨脂联素（APN）、直接胆红素（DB）、甘油三酯（TG）及三者联合对 2 型糖尿病（T2DM）患者大血管病变的诊断价值。方法 选取120例T2DM患者,根据是否合并大血管病变将其分为T2DM组（62 例）和 T2DM+大血管病变组（58 例）。比较两组的临床资料;采用非条件多因素逐步Logistic回归分析T2DM患者合并大血管病变的风险因素;绘制受试者工作特征（ROC）曲线评估APN、DB、TG及三者联合对T2DM患者合并大血管病变的诊断效能。结果 非条件多因素逐步Logistic回归分析结果显示,■是T2DM患者合并大血管病变的危险因素（P <0.05);■是T2DM患者合并大血管病变的保护因素（P <0.05）。ROC曲线分析结果显示,当APN ≤ 5.870 nmol/mL时,诊断T2DM患者合并大血管病变的曲线下面积（AUC）为0.718,敏感性为70.7%(95% CI:0.571,0.815）,特异性为61.3%(95% CI:0.480,0.713）;当DB ≤ 14.205 mol/L 时,AUC 为 0.772,敏感性为 74.1% (95% C...     

Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins

One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.     

Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus

Ukkola O, Savolainen MJ, Salmela PI, von Dickhoff K, Kesäniemi YA. Apolipoprotein B gene DNA polymorphisms are associated with macro-and microangiopathy in non-insulin-dependent diabetes mellitus. Clin Genet 1993: 44: 177–184. © Munksgaard, 1993 The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2%\pm2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of Xba I cleavage site). Patients with the X1 allele (absence of Xba I cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R +; homozygous for the presence of EcoR I cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R —; homozygous or heterozygous for the absence of the EcoR I cleavage site) (46.7%; p<0.02). When the polymorphisms Xba I (subjects homozygous for the absence of the cutting site = X +; subjects homozygous or heterozygous for the presence of the cutting site = X —) and EcoR I were combined, the prevalence of macroangiopathy was observed to be high in X + R + (80.0%) as compared with X + R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p<0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4\4 or E4/3), combined with either X+ or R +. Our findings suggest that variation at the apoB locus is one of the factors involved in predisposing diabetic patients to the development of arterial disease. As in previous studies the effect of the variation at the apoB gene on circulating lipid levels was observed. The data also support a role for the e4 allele of the apolipoprotein E gene as an important determinant of macroangiopathy in NIDDM.     

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil–based lipid therapy should be implemented in order to successfully halt and reverse IFALD.     

Chronic Intake of Energy Drinks and Their Sugar Free Substitution Similarly Promotes Metabolic Syndrome

Energy drinks containing significant quantities of caffeine, taurine and sugar are increasingly consumed, particularly by adolescents and young adults. The putative effects of chronic ingestion of either standard energy drink, Mother^TM (ED), or its sugar-free formulation (sfED) on metabolic syndrome were determined in wild-type C57BL/6J mice, in comparison to a soft drink, Coca-Cola (SD), a Western-styled diet enriched in saturated fatty acids (SFA), and a combination of SFA + ED. Following 13 weeks of intervention, mice treated with ED were hyperglycaemic and hypertriglyceridaemic, indicating higher triglyceride glucose index, which was similar to the mice maintained on SD. Surprisingly, the mice maintained on sfED also showed signs of insulin resistance with hyperglycaemia, hypertriglyceridaemia, and greater triglyceride glucose index, comparable to the ED group mice. In addition, the ED mice had greater adiposity primarily due to the increase in white adipose tissue, although the body weight was comparable to the control mice receiving only water. The mice maintained on SFA diet exhibited significantly greater weight gain, body fat, cholesterol and insulin, whilst blood glucose and triglyceride concentrations remained comparable to the control mice. Collectively, these data suggest that the consumption of both standard and sugar-free forms of energy drinks induces metabolic syndrome, particularly insulin resistance.     

高糖摄入对大鼠糖和脂质代谢及纤溶活性影响

①目的　观察高糖摄入对正常 Ｓｐｒａｇｕｅ Ｄａｗ ｌｅｙ（ Ｓ Ｄ）大鼠糖及胰岛素代谢、脂质代谢和纤溶活性的影响。②方法　将雄性 Ｓ Ｄ 大鼠１６ 只随机分为２ 组,实验组于饮水中添加蔗糖（１２０ｇ／ Ｌ）喂养４２ｄ,对照组给以正常饮水,每７ｄ 定时测量体质量（ Ｂ Ｗ）１ 次,实验最后１ｄ 取血测空腹血糖（ Ｆ Ｂ Ｇ）,空腹血清胰岛素（ Ｉ Ｎ Ｓ）,甘油三酯（ Ｔ Ｇ）,总胆固醇（ Ｔ Ｃ）,高密度脂蛋白胆固醇（ Ｈ Ｄ Ｌ Ｃ）水平及血浆纤溶酶原激活物抑制物１（ Ｐ Ａ Ｉ１）活性等指标。③结果与对照组相比,实验组 Ｆ Ｂ Ｇ,血清 Ｔ Ｇ 水平及血浆 Ｐ Ａ Ｉ１ 活性均升高（ｔ＝ ２．３６～４．７３, Ｐ＜ ０．０５,０．０１）;血清 Ｔ Ｃ及 Ｈ Ｄ Ｌ Ｃ水平两组差异无显著性（ｔ＝ １．３７,０．８４, Ｐ＞ ０．０５）;两组血清 Ｉ Ｎ Ｓ水平虽然差异无显著性（ｔ＝ ０．７７, Ｐ＞０．０５）,但是经协方差分析纠正体质量因素后,实验组与对照组相比存在高胰岛素血症（ Ｆ＝ ５．７４, Ｐ＜ ０．０５）;直线相关分析提示,实验组血清 Ｉ Ｎ Ｓ水平与 Ｂ Ｗ ,血清 Ｔ Ｇ水平及血浆 Ｐ Ａ Ｉ１ 活性呈高度正相关,对照组血清 Ｉ Ｎ Ｓ水平与 Ｂ Ｗ 及     

Lack of accumulation of midazolam in plasma and lipoprotein fractions during intravenous lipid infusions in patients on artificial respiration

Summary Severely ill patients often require total parenteral nutrition including intravenous liqid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed.Midazolam in the VLDL fraction was only 0.246 g·ml^–1, whereas the total plasma concentration averaged 1.101 g·ml^–1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 g·ml^–1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg·dl^–1 and VLDL-triglycerides from 77 to 155 mg·dl^–1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg·dl^–1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 g·ml^–1, 0.130 g·ml^–1, and 1.265 g·ml^–1, respectively. Cholesterol and albumin concentrations were not affected.The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.     

3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

Two siblings were found to be affected by longchain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C₆–C₁₄ 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized.