小鼠肝脏胰岛素受体的特异性敲除降低极低密度脂蛋白中三酰甘油分泌的研究

目的:建立肝组织特异性胰岛素受体急性缺失的动物模型,分析胰岛素信号缺失对三酰甘油代谢的影响。方法:在构建腺病毒时,利用Cre-LoxP系统机制,在Cre重组酶基因的上游插入肝组织特异性表达的白蛋白基因启动子。扩增纯化病毒,经小鼠尾静脉注射病毒14 d后,收集小鼠血浆,测定极低密度脂蛋白三酰甘油分泌速率,抽提肝脏脂质并用酶法检测脂质含量,用免疫印迹法分析胰岛素受体和脂代谢相关基因在肝脏内的表达。结果:成功构建了肝脏特异性胰岛素受体急性缺失动物模型。胰岛素信号缺失显著降低了小鼠肝脏的极低密度脂蛋白三酰甘油的分泌速度,同时也下调了肝脏脂肪酸合成相关基因和极低密度脂蛋白形成相关基因的表达。结论:肝脏胰岛素信号急性缺失降低极低密度脂蛋白中三酰甘油的分泌速度,这种变化可能和肝脏内脂肪酸的合成速度下降有关。     

Effects of Acipimox on the metabolism of free fatty acids and very low density lipoprotein triglyceride

The mechanism of triglyceride lowering by Acipimox, a nicotinic acid analogue, was examined in a group of five moderately hypertriglyceridemic male rhesus monkeys. Two experiments were designed to examine the effect of the drug on lipid and glucose metabolism in nondiabetic, insulin-resistant animals. A single dose of Acipimox (8 mg/kg) given with a meal lowered the plasma free fatty acids (FFA) significantly at 4 h (0.102±0.008 vs 0.154±0.020 g/l; ±SEM;P<0.03); however, FFA concentrations returned to control levels at 6 h. Chronic administration of Acipimox (16 mg/kg q. i. d.) for 2 months produced a 31% reduction in triglyceride concentration (P<0.05) and a significant decrease in low density lipoprotein (LDL)-cholesterol (P<0.04), without changes in insulin action as measured by the hyperinsulinemic euglycemic clamp. Fasting FFA concentrations were not significantly altered by chronic treatment (0.163±0.013 versus 0.140±0.034 g/l). Fatty acid metabolic studies indicated increases in FFA transport (203.7±59.1 versus 136.1±26.6 μEq/min;P<0.05), while FFA fractional clearance rate (FCR) was unchanged. Very low density lipoprotein triglyceride (VLDL-Tg) metabolic experiments, using [³H]glycerol, showed increases in production and FCR with the drug. Increased VLDL-Tg clearance, in spite of increased production of VLDL, appears to be the mechanism by which triglycerides are lowered upon chronic Acipimox administration.     

胰岛素,甘油三酯,血糖对糖尿病患者血浆内皮素的影响

目的　探讨糖尿病患者血浆内皮素的影响因素。方法　对照组４３ 人，糖尿病组４５例，测定空腹及早餐后２ 小时的内皮素、胰岛素、甘油三酯、胆固醇、血糖。计算体重指数。结果　糖尿病组内皮素比对照组显著性增高（ Ｐ＜０ ．０１）。糖尿病组：空腹、餐后的内皮素与胰岛素正相关（ Ｐ＜０．０５ ，Ｐ＜ ０．０１）。空腹内皮素与甘油三酯无显著性相关，餐后内皮素与甘油三酯正相关（ Ｐ＜ ０ ．０１） 。空腹、餐后内皮素与血糖正相关（ Ｐ＜ ０．０１） 。空腹、餐后内皮素与胆固醇均无显著性相关。内皮素与体重指数无显著性相关。结论　糖尿病患者血浆内皮素比健康人增高。胰岛素、甘油三酯、血糖是刺激糖尿病患者血浆内皮素增高的重要因素。餐后上述三种因素对糖尿病患者血浆内皮素的作用增强。     

CER-001, a HDL-mimetic,stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice

Objective

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr^−/− mice after short-term multiple-dose infusions.

Approach and results

CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10 mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively.

Conclusion

These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr^−/− mice upon a short-term multiple dose treatment.     

Determinants of lipoprotein(a) levels in a middle-aged working population

BACKGROUND: The association between blood lipids, apolipoproteins, fibrinogen,life-style-related factors and lipoprotein(a) was assessed ina cohort of middle-aged men. METHODS: Male employees, working in local industry, were invited to participatein a health survey at their worksite. After exclusion of ninepersons with prevalent diabetes and 14 subjects with a historyof myocardial infarction or angina, data were available on 720healthy Caucasian men. RESULTS: Lipoprotein(a) concentration was measured using an enzyme-linkedimmunosorbent assay (ELISA), and distribution was found to behighly skewed with a median level of 9mg. dl^–1 (mean level23.1 mg . dl^–1). The percentage of subjects with lipoprotein(a)levels higher than 30 mg. dl^–1 was 23.6%. Univariate analysisshowed a significant association between lipoprotein(a) andage, total cholesterol, apolipoprotein B and fibrinogen. However,no relationship was found with body mass index, waist to hipratio, smoking, blood pressure, alcohol consumption, diet, HDLcholesterol, apolipoprotein Al and apolipoprotein E concentrationor apolipoprotein E polymorphism. In multivariate analysis,In-transformed lipoprotein(a) correlated positively with apolipoproteinB (P<0.0001) and fibrinogen (P=0.004). Proportional changesin lipoprotein(a) concentration were predicted in relation tospecified changes in biochemical and lifestyle variables. A20 mg. d^–1 increase in apolipoprotein B and a 75 mg. dl^–1increasein fibrinogen levels were estimated to increase lipoprotein(a)concentration by 29.4% and 2l.5% respectively. CONCLUSIONS: Our data confirm the existence of an independent associationbetween lipoprotein(a) and fibrinogen and give evidence forcorrelation with apolipoprotein B.     

The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia

The reduction of elevated low density lipoprotein (LDL) cholesterol concentrations in patients with Type II hyperlipoproteinemia leads to improved cardiovascular morbidity and mortality. Two agents which may be of value in treating hypercholesterolemia are mevinolin and neomycin. Since these drugs lower cholesterol levels through complementary mechanisms, we evaluated the effects of mevinolin and combined mevinolin-neomycin treatment on plasma lipoprotein concentrations in 21 type II hyperlipoproteinemic patients. Mevinolin reduced total and LDL cholesterol concentrations by 24% and 31% respectively (P < 0.001) and 81% of the patients reduced their LDL cholesterol levels to less than 200 mg/dl. Although the addition of neomycin to mevinolin treatment further lowered total (5%) and LDL (4%) cholesterol concentrations, it also reduced HDL cholesterol levels (19%) (P < 0.05). Therefore mevinolin normalizes the plasma lipid concentrations in patients with type II hyperlipoproteinemia and combined mevinolin and neomycin treatment offers no advantage over mevinolin-only therapy. In addition, these findings emphasize the importance of determining the HDL cholesterol level to fully evaluate the effects of hypolipidemic therapy.     

Effect of ethnicity on disease activity and physical function in psoriatic arthritis in a multiethnic Asian population

Geographic differences in manifestation of psoriatic arthritis (PsA) could be related to differences in genetic or environmental factors. We aimed to compare the disease activity and functional status using validated outcome measures among patients with PsA of different ethnicities living in the same environment. We performed a cross-sectional study on consecutive patients with PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria from a single center. Sociodemographic data, clinical variables, and patient-reported outcomes were collected using a standardized protocol. Disease activities were assessed by validated composite scores: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), Composite Psoriatic Disease Activity Index (CPDAI), and minimal disease activity (MDA). Physical function was assessed with Health Assessment Questionnaire (HAQ) and the Medical Outcome Study Short-Form 36 (SF36) physical function subscales. Linear regression analyses were performed to identify variables associated with disease activities and physical function. Ninety-eight patients (51.5%, men) with mean (±SD) age and duration of PsA of 51.5 ± 13.8 and 5.5 ± 8.4 years were recruited. Indian was overrepresented compared with the national distribution of ethnicities. Compared to Chinese, Indian patients were more likely to be using biological therapies, have higher tender joint count, and worse enthesitis. Higher proportion of Indians had higher disease activity categories measured by cDAPSA, CPDAI, and MDA and had poorer physical function. In the multivariable analysis, ethnicity was significantly associated with HAQ and SF36-PF. Compared to Chinese, Indians with PsA living in the same environment had worse disease activity and physical function measured by validated outcomes.     

2型糖尿病血浆动脉硬化指数预测发生冠心病的价值

目的探讨2型糖尿病合并冠心病与血浆动脉硬化指数(atherogenicindexofplasma,AIP)的关系。方法2型糖尿病住院病人82例,其中糖尿病合并冠心病52例,糖尿病无合并冠心病30例,进行冠状动脉造影。测量身高和体重计算体质量指数(bodymassindex,BMI);测量血脂,计算AIP,并进行统计学处理。结果2型糖尿病合并冠心病组BMI(26.1±1.2)kg/m2,高于单纯2型糖尿病组(23.8±0.9)kg/m2。2型糖尿病合并冠心病组甘油三酯(5.8±1.6)mmol/L,高于单纯2型糖尿病组(4.8±0.9)mmol/L;2型糖尿病合并冠心病组低密度脂蛋白胆固醇高于单纯2型糖尿病组,但高密度脂蛋白胆固醇低于单纯2型糖尿病组。2型糖尿病合并冠心病组AIP为0.51±0.23,高于单纯2型糖尿病组0.28±0.19,差异有统计学意义(P<0.05)。Logistic回归分析显示:2型糖尿病人是否出现冠心病与AIP相关(β0=-2.62,β1=8.069,SE=1.86,Wald=18.8,P=0.000)。结论AIP改变可作为评价2型糖尿病病人并发冠心病的危险性的指标。     

Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein -493G/T polymorphism on plasma lipoprotein levels in men

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) −493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP −493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP −493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein–lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm²) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein–lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP −493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter.     

The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia

Summary Using I¹³¹ VLDL selectively labelled in the B-apoprotein and I¹²⁵ LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72–83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21–28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.     

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

To analyse the relationship of PAI-1 plasma levels to echographically determined liver steatosis and cardiometabolic risk factors in a randomly selected sample of 254 adult male participants of the Olivetti Heart Study. Accounting for age and ongoing pharmacological treatment, PAI-1 levels were directly (P < 0.005) associated with body mass index (BMI), waist circumference (WC), serum triglyceride (TG), total cholesterol, insulin, homeostasis model assessment index, gamma-glutamyl transpeptidase and peritoneal fat. At multiple linear regression (MLR) analysis, measures of adiposity and TG exerted significant and quantitatively similar effects on PAI-1 levels. A progressive rise in PAI-1 level was detected with increasing degree of steatosis. A stepwise MLR model was used to evaluate the relative power of cardiometabolic risk factors and liver steatosis on PAI-1 levels. Adjusting for alcohol intake, BMI, WC and peritoneal fat were alternatively included in the model with other variables found to be significantly associated with plasma PAI-1 level. Liver steatosis, serum TG and various indexes of adiposity each had a significant independent impact on PAI-1 plasma level and explained overall 23% of its variability. Abdominal fat, liver steatosis and serum TG levels were significant and independent determinants of PAI-1 plasma level in an unselected sample of adult male population upon adjustment for age and therapy. The Olivetti Heart Study Research Group: P. Strazzullo (coordinator), G. Barba, F. P. Cappuccio, E. Farinaro, F. Galletti, A. Siani.     

Cholesteryl ester transfer activity : Localization and role in distribution of cholesteryl ester among lipoproteins in man

The cholesteryl ester exchange/transfer protein is involved in the transport of cholesteryl ester from high density lipoproteins (HDL) to very low density lipoproteins (VLDL) and low density lipoproteins (LDL). Localization of cholesteryl ester transfer activity (CETA) in plasma was studied by measuring CETA in various delipidated fractions from a single step density ultracentrifugation gradient of plasma. CETA was measured in an in vitro system by calculating the exchange of cholesteryl ester in a standard mixture of [3H]CE-HDL and LDL. The method used for the delipidation of plasmas and fractions to be tested was critical. Optimal results were obtained by delipidation with diisopropylether-butanol (60: 40, v/v) at O degrees C. The bulk of CETA was detected in HDL3 (1.125 less than d less than 1.210 g/ml) when the lipoproteins were separated by single-step density gradient ultracentrifugation and in the 'lipoprotein-free' fraction (d greater than 1.250 g/ml) when the lipoproteins were separated by flotation ultracentrifugation including two washes. To determine whether CETA plays a role in the distribution of cholesteryl ester among the various lipoproteins, it was measured in whole plasma from normal and hyperlipidemic subjects. Plasma was delipidated before the assay in order to prevent bias due to variation of cholesterol content. CETA was higher in delipidated plasma of hyperlipidemic subjects (117.3 +/- 36.5 nmol CE/ml/h) than in delipidated plasma of normolipidemic controls (68.7 +/- 17.6 nmol CE/ml/h) (P less than 0.005). A positive correlation (r = 0.80, P less than 0.005) was found between CETA and (VLDL + LDL) cholesterol levels. A negative correlation (r = 0.57, P less than 0.05) existed between CETA and HDL cholesterol. This correlation was found both in the group as a whole and within the normal and the hyperlipidemic groups separately. The activity of the cholesteryl ester transfer appears to be a regulatory factor in the distribution of cholesteryl ester over the various lipoproteins.     

Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy.

Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with regard to LDL metabolism and composition. The FCHL patients had higher LDL levels than healthy controls (5.4 +/- 1.4 vs. 3.7 +/- 0.7 mmol l-1; P < 0.005) and a higher rate of production of the lipoprotein (15.8 +/- 3.1 mg kg-1 d-1 in FCHL vs. 13.1 +/- 1.8 mg kg-1 d-1 in the normals; P < 0.005). The fractional catabolic rate of LDL was low-normal in the FCHL patients, with a high level of interindividual variation. The actual individual LDL cholesterol level within the FCHL patient group appeared to be more closely associated with the LDL apoB FCR value than the rate of production of the particle. Analysis of the LDL particles from FCHL patients revealed a relative enrichment in triglycerides, while the cholesterol content of the lipoprotein was normal. Institution of acipimox therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 +/- 3.5 mg kg-1 d-1) to a more normal level (13.9 +/- 4.0 mg kg-1 d-1; P = 0.08), while the FCR did not change significantly. In conclusion, patients with FCHL show an apparent overproduction of LDL apoB, while the actual degree of LDL elevation appears to be dependent on the clearance capacity of the lipoprotein, measured as LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be managed by treatment with the nicotinic acid analogue acipimox.     

Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet

The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men (mean age, 35.7 +/- 11.4 years; body mass index, 29.0 +/- 5.1 kg/m2) were randomly assigned to either a high-CHO diet (CHO, 58%; fat, 26%; n = 23) or a high-MUFA diet (CHO, 45%; fat, 40%; MUFA, 22.5%; n = 24), which they consumed for 6 to 7 weeks. Fasting and postprandial lipemia after an oral fat load and fasting plasma apo C-III were measured at the beginning and at the end of the dietary intervention. Ad libitum consumption of the high-CHO diet induced a significant reduction in body weight (-2.6%, P < .0001), but had no impact on plasma apo C-III concentrations and on fasting and postprandial plasma TG levels. In contrast, ad libitum consumption of the high-MUFA diet also resulted in a significant reduction in body weight (-2.3%, P < .01) as well as in significant reductions in plasma apo C-III (-11%, P = .05) and fasting plasma TG (-17%, P < .01). Diet-induced variations in plasma apo C-III concentrations were correlated with changes in fasting and postprandial TG levels both in the high-CHO (r > 0.70, P < .001) and the high-MUFA groups (r > 0.42, P < .05). These results indicate that variations in plasma apo C-III levels are strong correlates of the fasting and postprandial plasma TG responses to high-MUFA and high-CHO diets.     

不同糖代谢异常患者血浆载脂蛋白A5水平的变化及其临床意义

目的 通过比较不同糖耐量人群血浆载脂蛋白A5（ApoA5）、脂联素（APN）及TG水平,探讨其相互关系,以及ApoA5及APN降低TG的可能机制. 方法 选取新诊断T2DM患者（T2DM组）35例,IGR者（IGR组）30例及正常对照者（NGT组）35名,行静脉葡萄糖耐量试验（IVGTT）.ELISA测定空腹ApoA5及APN水平;比色法测定FFA.稳态模型评估胰岛素抵抗指数（HOMA-IR）及胰岛β细胞功能指数（HOMA-β）.探讨ApoA5与APN、血脂、FFA、HOMA-IR及HOMA-β的关系. 结果 （1）T2DM、IGR组ApoA5及APN水平低于NGT组（P＜0.05）,且T2DM组较IGR组降低更明显（P＜0.05）.（2）T2DM、IGR组TG、FFA、2 hFFA、LDL-C、FPG、2 hPG、FIns、HOMA-IR水平高于NGT组（P＜0.05）,且T2DM组较IGR组升高更明显（P＜0.05）.（3） ApoA5与TG、TC、FFA、2 hFFA、LDL-C、FPG、2 hPG、FIns、HOMA-IR、BMI及WHR呈负相关;与APN、HDL-C及HOMA-β呈正相关.（4）多元逐步回归分析显示,APN、TG、FFA、WHR及HOMA-IR是ApoA5的独立影响因素. 结论 低ApoA5及APN水平可能是IGR时期的早期敏感指标,低ApoA5及APN水平不能有效抑制血中FFA水平,可能导致高甘油三酯血症（HTG）及IR,从而共同导致IGR及T2DM的发生发展.     

Impact of race and ethnicity on counseling for alcohol consumption: a population-based, cross-sectional survey

BACKGROUND: Counseling for alcohol use is of proven utility, but whether disparities in provision of counseling exist is uncertain. METHODS: Using the 1999 Behavioral Risk Factor Surveillance System, a population-based telephone survey, we examined participant-reported physician counseling for alcohol use among 15,498 adults in 5 U.S. states. Participants reported their usual alcohol intake, risky drinking (intake of 5 or more drinks on occasion, greater than 60 drinks per month, or driving after drinking), and whether a doctor had spoken with them about alcohol use. RESULTS: Race and ethnicity were strongly associated with reported receipt of alcohol counseling. Compared with whites, black and Hispanic adults had 2-fold higher odds of reporting receiving counseling among all participants, among problem drinkers, and among abstainers. There were modest differences according to sex, income, self-reported health, and education, but not body mass index. Multivariable adjustment and restriction to participants who reported a recent checkup did not alter these findings. No such disparity was noted for general diet counseling. CONCLUSIONS: Clear racial and ethnic differences exist in physician counseling for alcohol use, with higher prevalence estimates among racial and ethnic minority populations. Although the cause of these differences is uncertain, systematic application of preventive medical services such as alcohol screening and counseling is needed for all patients.     

Association of a polymorphism in the gene encoding phosphoenolpyruvate carboxykinase 1 with high-density lipoprotein and triglyceride levels

Aims/hypothesis Phosphoenolpyruvate carboxykinase (PCK) is the key enzyme involved in the regulation of gluconeogenesis. The aim of this study was to identify genetic polymorphisms in potential candidate genes for type 2 diabetes by sequencing all exons in the PCK genes (PCK1 and PCK2), and examining the association with type 2 diabetes and diabetic phenotypes in a Korean population (775 type 2 diabetic patients and 316 normal control subjects).Materials and methods Twenty-two polymorphisms in PCK1 and PCK2 were identified in a Korean population (n=24) by direct DNA sequencing. The TaqMan genotyping method was applied for genotyping the remainder of the study population. Associations of PCK polymorphisms with the risk of type 2 diabetes and diabetic phenotypes were analysed using logistic and multiple regressions, adjusting for age, sex and BMI.Results Although no significant associations between the genetic polymorphisms in PCK genes and the risk of type 2 diabetes were detected, in further haplotype analysis, one of the common haplotypes, PCK1 ht3, revealed susceptibility to type 2 diabetes (p=0.006). One 3 untranslated region (UTR) single nucleotide polymorphism (SNP) also showed an association with HDL levels among non-diabetic control subjects: individuals homozygous for the major allele (T/T) had the lowest HDL level (1.11±0.32 mmol/l), heterozygotes (T/C) had an intermediate level (1.27±0.37 mmol/l), and those homozygous for the minor allele (C/C) had the highest level (1.39±0.28 mmol/l) (p=0.000003). This 3 UTR SNP was also associated with triglyceride levels, with a lower triglyceride level observed among individuals who were homozygous for the minor allele (C/C) than among those who were not.Conclusions/interpretation The strong genetic association of HDL and triglyceride levels with variation/haplotype information identified in this study would be useful for further genetic epidemiological studies of this important gene.Electronic supplementary material Supplementary material is available for this article at and accessible for authorised users.     

Postprandial plasma glucose,insulin, glucagon and triglyceride responses to a standard diet in normal subjects

Summary Postprandial plasma glucose, insulin and triglyceride responses were determined in 12 normal subjects (7 male and 5 female) fed a standard diet composed of typical American foods; the three meals were identical for each subject. A significant post-prandial rise in glucose and insulin was observed. They were closely related temporally in the early post-absorptive period. However, in the late post-absorptive phase insulin decline was generally slower than the glucose decline. A considerable difference in the glucose and insulin response was observed between males and females. Fasting plasma glucose and insulin concentrations were lower in the women. Following each meal the peak plasma glucose was lower in the women, but the difference was significant only following breakfast (p < 0.02). The area under the glucose curve following breakfast was also lower (p < 0.01) in the women. In the men the maximal postprandial glucose concentration and the postprandial glucose area remained stable throughout the day, but there was an increase in peak insulin concentration and insulin area after dinner. In contrast, in the women the maximal postprandial glucose concentration and the postprandial glucose area increased throughout the day, but the peak insulin concentration and insulin area did not change. Plasma triglycerides increased with breakfast and remained elevated throughout the day. Both fasting and postprandial mean triglycerides were higher in the men, but this did not reach statistical significance. The circulating pancreatic glucagon concentration, determined in 4 subjects, was unaffected by meals and remained stable throughout the day.     

Rationale and design of the ETN-STEP (Early administration of Tirofiban in mid to high risk patients with non-ST elevation acute coronary syndrome referred for percutaneous coronary intervention) project: A multi-center, randomized, controlled clinic trial in Chinese patients

As a member of Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, Tirofiban had been shown to improve myocardial reperfusion and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), but the optimal timing of administration of Tirofiban remains unclear. In order to compare the effects of upstream versus downstream administration of Tirofiban in Chinese patients with mid to high risk, non-ST elevation acute coronary syndrome (ACS) referred for PCI, a multicenter, randomized, controlled, prospective study will be conducted. A total of 500 mid to high risk, non-ST-segment elevation myocardial infarction (NSTEMI) ACS patients will be recruited for this study. Patients will be randomized to Tirofiban upstream administration group (initiated 12 h before PCI) and Tirofiban downstream administration group (initiated at cath-lab after angiography). Thrombolysis in myocardial infarction (TIMI) flow grades, TIMI myocardial perfusion grades (TMPG), and Corrected TIMI frame counting (CTFC) before and after PCI, as well as clinical outcomes during the hospital stay, and within 30 days after PCI will be compared between the two groups. This study will provide evidence on the optimal timing for initiating administration of Tirofiban in mid to high NSTEMI ACS subjects undergoing PCI.