Effect of a single high-fat meal on endothelial function in patients with the metabolic syndrome: role of tumor necrosis factor-alpha

Background and aimsA single high-fat meal may induce endothelial activation and dysfunction in both normal subjects and in patients with type 2 diabetes. The aim of this study was to assess the effect of a high-fat meal on endothelial function in patients with the metabolic syndrome.Methods and resultsTwenty-five patients with the metabolic syndrome (ATP III criteria) were matched for sex, age and body mass index with 25 subjects without the metabolic syndrome. All subjects ate under supervision a high fat meal (760 calories) with 59% energy from fat, 12% energy from protein and 29% energy from carbohydrates. Compared with the control group, subjects with the metabolic syndrome had reduced endothelial function, as assessed with the l-arginine test, and higher circulating levels of TNF-α. Following the high-fat meal, both triglyceride and TNF-α levels increased more in subjects with the metabolic syndrome than in subjects without, while endothelial function decreased more in subjects with the metabolic syndrome. There was a significant relation between increases in TNF-α levels and decreases in endothelial function score in subjects with the metabolic syndrome (r = −0.39, P = 0.03).ConclusionTNF-α levels are increased in subjects with the metabolic syndrome; moreover, a high-fat meal produces further increase in its levels associated with endothelial dysfunction.     

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

Postprandial lipemia (PPL) is associated with impaired endothelial function and inflammation. Acute exercise reduces PPL in adults. This investigation examined the effect of an acute bout of exercise on postprandial changes in triglycerides (TG), glucose, insulin, inflammation [white blood cell count (WBC), interleukin-6 (IL-6) tumor necrosis factor-alpha, C-reactive protein (CRP)] and endothelial activation [soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1)] following a high-fat meal in adolescents. Ten normal weight (NW) (BMI, 20.9 ± 1.7 kg m⁻²; 15.6 ± 0.7 years) and eight overweight (OW) (BMI, 28.3 ± 3.6 kg m⁻²; 15.9 ± 0.4 years) adolescent boys underwent two 6-h oral fat tolerance tests (OFTT) separated by 7–10 days. On the evening prior to each OFTT, subjects either rested or completed a treadmill exercise bout (65% 600 kcal expended). Exercise reduced (P < 0.01) the postprandial TG area under the curve by ~20% in the NW and OW groups. The postprandial glucose and insulin response did not differ between the control and exercise trials or between the NW and OW groups. Circulating leukocytes and plasma IL-6 levels increased (P < 0.01) in the NW and OW groups 6 h following the OFTT in both experimental conditions. There were no changes in CRP, sVCAM-1 or sICAM-1 following the OFTT and there were no differences between experimental condition or NW and OW groups. In conclusion, a moderate exercise bout prior to a high-fat meal effectively reduces postprandial TG concentrations to a similar degree in both NW and OW adolescents, but does not reduce the concomitant postprandial increase in WBC or IL-6.     

正常空腹血糖与心血管疾病危险因素的相关性研究

目的探讨正常空腹血糖与心血管疾病及其危险因素的相关性。方法入选对象按空腹血糖结果分为以下4组:3.9~4.4 mmol/L为A组;4.5~5.1 mmol/L为B组;5.2~5.6 mmol/L为C组;5.7~6.1 mmol/L为D组。计算各组异常临床变量的相关指标及与空腹血糖的线性关系,比较各组间的差异性,并通过Logistic回归分析探讨正常空腹血糖与心血管危险因素间的关系。结果 (1)4组年龄、体质指数(BMI)、腰围(WC)、三酰甘油(TG)、总胆固醇(TC)、收缩压(SBP)、舒张压(DBP)及平均压间差异均有统计学意义(P<0.05),两两比较显示D组年龄、TG明显高于A、B、C组,差异有统计学意义(P<0.05);D组TC明显高于B、C组,差异有统计学意义(P<0.05);C、D组SBP、DBP、平均压明显高于B组,差异有统计学意义(P<0.05)。4组患者的BMI比较差异有统计学意义(P<0.05),两两比较显示:D组与B组比较差异有统计学意义;C组与A、B组比较差异有统计学意义。4组患者女性WC间差异有统计学意义(P<0.05),两两比较显示A组与B、C、D组差异有统计学意义,B组与C、D...     

三酰甘油与青年冠状动脉粥样硬化病变关系的研究

目的 探讨三酰甘油(TG)对青年冠心病患者冠状动脉狭窄严重程度及病变血管范围的影响.方法 对行经皮冠状动脉介入治疗(PCI)的93例青年冠心病患者(<45岁)的临床资料进行回顾性分析.按TG测定结果分为I组(TG<1.70 mmol/L,36例)、Ⅱ组(1.70 mmol/L≤TG≤2.25mmol/L,19例)、Ⅲ组(TG>2.25mmol/L,38例),对比各组冠状动脉狭窄严重程度及病变血管范围的差异.结果 93例患者中男性占94.62%(88/93)、吸烟者占83.87%(78/93).III组的总胆固醇、非高密度脂蛋白胆固醇明显高于I组(P=0.006、0.003),三组间低密度脂蛋白胆固醇、高密度脂蛋白胆同醇及空腹血糖比较差异无统计学意义(P=0.648、0.795、0.247).三组患者的冠状动脉病变血管范围、狭窄严重程度比较差异无统计学意义(P=0.241、0.879).结论 高TG血症对青年冠心病患者冠状动脉狭窄严重程度及病变血管范围无影响,不是冠心病患者病情严重程度的决定性因素.     

Modification of the oxidative stress biomarker AOPP assay: application in uremic samples

BACKGROUND: The levels of advanced oxidation protein products (AOPP), a plasma protein biomarker used to assess oxidative stress, are elevated in patients with chronic kidney disease (CKD). However, this apparent elevation is to a large extent due to assay interference (mostly by triglycerides which are usually markedly elevated in CKD). We therefore developed and tested a modified version of the AOPP assay to minimize the impact of this interference. METHODS: Plasma levels of AOPP, lipids, proteins and various biomarkers of inflammation and oxidative stress were analyzed in 218 prevalent hemodialysis patients and 13 healthy controls using the established original (oAOPP) assay and following precipitation of plasma lipids using dextran sulphate (modified assay, mAOPP). The modified results were validated against a lipid extraction procedure using ether/butanol. RESULTS: The modified assay decreased the levels of triglycerides and AOPP by 87% and 38%, respectively. Whereas oAOPP values correlated strongly with triglycerides, no such correlation was seen with mAOPP. The mAOPP levels correlated significantly with the oxidative stress markers 8-oxo-dG and pentosidine, whereas no such correlations were found for oAOPP. CONCLUSIONS: The oAOPP concentration is largely overestimated in plasma samples due to lipid interferences. Precipitation of triglycerides before analysis yields markedly lower mAOPP values which more accurately reflect oxidative stress. Based on these results we propose that AOPP should be analyzed using the modified assay, which is a cheap, simple and fast method.     

Multiple Benign Symmetric Lipomatosis—A Differential Diagnosis of Obesity. Is There a Rationale for Fibrate Treatment?

Multiple benign symmetric lipomatosis (MSL) is characterized by a rapid progression of multiple, symmetric nonencapsulated fat masses in the face, neck, and extremities. The lipomas are thought to be the result of defective brown adipose tissue (BAT). In up to 90% MSL is associated with chronic alcohol abuse. Prognosis depends on the concomitant presence of a neuropathy with a mortality of 25.8%. Therapeutic options are limited to alcohol abstinence and surgical interventions. We report here about a 53-year-old MSL patient who increased his body weight by 37 kg over 10 years. Multiple lipectomies were performed, but disease progressed. We treated him with fenofibrates (200 mg/day). Disease progression discontinued and circumferences of abdominal adipose tissue reduced. Fibrates, peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, are pleiotropic hypolipidemic drugs, and might have worked by suppression of protein expressions involved in the architecture of BAT keeping it in a quiescent state. H. Zeitler and G. Ulrich-Merzenich contributed equally to this work.     

Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1

BACKGROUND: The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial. METHODS: The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. RESULTS: At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP. CONCLUSIONS: This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment.     

特技飞行前后血糖、血脂、载脂蛋白A_1、B、心肌酶及免疫球蛋白的变化

为探讨特技飞行是否会增加冠心病发病的危险因素，是否能损伤心肌细胞以及是否能使某些体液免疫功能发生变化，对20例飞行员进行复杂特拉飞行前（6：00，空腹）、飞行后即刻（10：00）、6h（16：00）及24h（次日10：00）血糖、血清胆固醇（TC）、甘油三脂（TG）、载脂蛋白A1（apoA1）、B（apoB）、GOT、CPK、LDH及IgA、IgG、IgM检测。结果显示：①飞行后即刻血糖、TG及apoA1明显升高，与飞行前及飞行后6h、24h比较，均有显著性差异（P＜0．05）；②飞行后即刻血清apoB／apoA1比值与飞行前及飞行后6h、24h比较，均无显著性差异（P＞0．05）；③其余各项指标，飞行前后均无显著性变化（P＞0．05）。本研究结果提示，短时间特技飞行不会增加冠心病发病的危险因素，不会损伤心肌细胞，亦不会影响以上体液免疫功能。     

空腹甘油三酯正常者脂肪负荷试验的动态观察

目的：探讨空腹ＴＧ正常的人在脂肪餐后的血脂水平的动态变化。方法：采用６３．９ｇ／ｍ２体表面积的脂肪餐，对５８名ＴＧ　≤１．７０　ｍｍｏｌ／Ｌ的人进行脂肪代谢的研究，根据年龄分为老年组、中年组和青年组，又依据餐后４ｈ、８ｈＴＧ浓度和ＴＧ－ＡＵＣ分为餐后ＴＧ正常组和异常组。结果：脂肪餐后的ＴＧ水平明显较空腹增高（Ｐ　＜０．００１），餐后各时间点之间的ＴＧ无显著性差异（Ｐ　＞０．０５），平均达峰时间为３．９８ｈ，８ｈ未能完全恢复至空腹水平。青、中、老年组达峰时间和ＴＧ－ＡＵＣ依次递增，仅青年组和老年组达峰时间的差异有显著性意义（Ｐ　＜０．０５）。餐后ＴＧ异常组各时间点的ＴＧ水平均明显高于正常组（Ｐ　＜０．００１）。餐后ＴＣ、ＨＤＬ－Ｃ和ＬＤＬ－Ｃ在２　ｈ时都有一个低谷期，８　ｈ时基本恢复正常。结论：空腹ＴＧ正常者中有一些人，在高脂餐后可出现ＴＧ代谢异常；ＴＧ廓清速率随着年龄的增加而减慢。     

Ten-year change in serum uric acid and its relation to changes in other metabolic risk factors in young black and white adults: the CARDIA study

Elevated serum uric acid is commonly seen in association with obesity, glucose intolerance, hypertension and dyslipidemia. There is currently no satisfactory explanation for the relation of uric acid and the metabolic syndrome (MetSyn). This study aimed to evaluate the relations of change in serum uric acid with changes in components of the MetSyn in young adults. We studied 1,249 male and 1,362 female black and white subjects aged 17–35 years (baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, which attended a 10-year follow-up. Metabolic factors assessed at both time periods included BMI, waist circumference, blood pressure, fasting glucose, insulin, and lipids. Confounders examined (baseline and change variables) were serum creatinine, alcohol, smoking, physical activity, and oral contraceptives. Mean uric acid increased the most in black males (+0.5 mg/dl), followed by white males (+0.3 mg/dl) and black females (+0.2 mg/dl) (all P < 0.01), with the least change among white females (+0.1 mg/dl) (ns). Although change in all of the metabolic factors was associated with change in uric acid in the anticipated directions, in multivariable analyses only BMI and triglycerides had a significant independent association with uric acid in all race-sex-groups. Among confounders, only change in serum creatinine showed a strong independent association with uric acid. In conclusion, besides weight gain and renal excretion, increasing uric acid concentrations in young adults are strongly related to corresponding changes in triglycerides. The correlation of uric acid and triglycerides was found within the normal range and could not be explained by obesity.