Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects.

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.     

小肠脂酸结合蛋白基因多态性与2型糖尿病合并冠心病的关系

为了解小肠脂酸结合蛋白基因（ＦＡＢＰ２）多态性与２型糖尿病合并冠心病（ＣＨＤ）的关系。方法２型糖尿病无冠心病组（ＤＭ－１）６４型糖尿病合并冠心病组（ＤＭ－２）８２例,非糖尿病冠心病组６２例,正常对照组６０例。应用聚合链酶反应（ＰＣＲ）技术检测２６８例对象ＦＡＢＰ２ＨｈａⅠ位点的限制性片段长度多态性（ＲＦＬＰｓ）。结果（１）武汉地区汉族人存在ＰＡＢＰ２ＨｈａＩ多态性位点,可产生Ｔｈｒ５４（－）和Ｔｈ     

Lipoprotein(a) is associated with coronary heart disease independent of metabolic syndrome

AIM: To assess (i) the association between lipoprotein(a) [Lp(a)] with the likelihood of coronary heart disease and metabolic syndrome (MS) and (ii) its covariates in Turkish adults. METHODS: Cross-sectional evaluation of 1309 adults, who had serum Lp(a) determinations by Behring nephelometry, and followed for a mean 1.0 year. MS was defined by ATPIII criteria modified for male abdominal obesity. RESULTS: Mean age of the sample was 56.8+/-11.3 years. After adjustment for sex, age, and smoking status, log-transformed Lp(a) levels were associated significantly with coronary heart disease likelihood in both sexes combined [odds ratio: 1.53 (95% confidence interval: 1.06; 2.20)]. This association persisted after additional adjustment for MS [odds ratio: 1.57 (95% confidence interval: 1.09; 2.26)]. The Lp(a) mid-tertile (5-17 mg/dl), accompanied by significantly lower serum triglycerides than the two remaining tertiles, was inversely associated significantly with MS in either sex; in women, this association was independent of waist circumference. In a linear regression comprising seven variables, excepting total cholesterol, only gamma-glutamyltransferase in women (P=0.002) and waist circumference (P=0.057) in men were inverse covariates of modest magnitude of Lp(a). CONCLUSION: Coronary heart disease likelihood, significantly associated with Lp(a) concentrations, is independent of MS and insulin resistance. Suggestive evidence was provided that intermediary Lp(a) concentrations, when accompanied by the presence of MS, could accelerate progression of vascular disease, especially in women.     

代谢综合征患者血尿酸水平与冠心病的关系

将 769例不同程度代谢异常患者分为冠心病组和非冠心病组,分析血尿酸在不同代谢异常状态下与冠心病的关系。结果显示,在缺乏其他代谢因素影响时,尿酸可能与冠心病的发生有一定关联,但并非冠心病的独立危险因素。     

Non-traditional markers of atherosclerosis potentiate the risk of coronary heart disease in patients with type 2 diabetes and metabolic syndrome

Background and aimsThe aims of this study were to establish the prevalence of metabolic syndrome (MS), in type 2 diabetes mellitus (DM), according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and to assess the association of MS with other cardiovascular (CV) risk factors in these patients.Methods and resultsA cross-sectional study was conducted in 1610 patients with type 2 DM. Glycated hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), uric acid, fibrinogen, creatinine, and albumin/creatinine ratios were measured. The risk of coronary heart disease (CHD) was calculated using the UKPDS Risk Engine.Seventy percent of the diabetic population met the criteria for MS; central obesity and hypertension were the most common criteria. Subjects with MS had higher levels of HbA1c, LDL-C, non-HDL-C, uric acid, and fibrinogen compared to patients without MS. Similarly, microalbuminuria and a high triglyceride (Tg)/HDL-C ratio (a marker of small LDL-C) occurred more frequently in patients with MS. When patients with no history of CHD events were considered, mean CHD risk was greater in those with, than those without, MS.ConclusionsMS is highly prevalent in type 2 DM and is commonly associated with non-traditional CV risk factors. The diagnosis of MS seems to confer additional CHD risk in patients with type 2 diabetes.     

Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men

The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption.     

非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性分析

目的 研究非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性.方法 选取非酒精性脂肪肝106例,非酒精性脂肪肝合并代谢综合征58例,单纯肥胖32例,健康体检42例作为对照组.测定体重指数（BMI）和腰臀比（WHR）,检测空腹血糖（FBS）、丙氨酸氨基转移酶（ALT）、胆固醇（TC）、甘油三脂（TG）和高密度脂蛋自（HDL）等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素（FINS）水平,计算胰岛素抵抗指数（HOMA）.同时酶联免疫法测定血清脂联素水平,并用相关及多元回归分析脂联素与各参数的相关性.结果 非酒精性脂肪肝组BMI、ALT、TC、TG、FBS、FINS和HOMA均较正常对照组高,HDL和脂联素水平较正常对照组低;非酒精性脂肪肝合并代谢综合征组胰岛素抵抗程度较非酒精性脂肪肝组更严重,脂联素水平更低.单纯肥胖组ALT、TC高于对照组,脂联素水平有下降趋势.非酒精性脂肪肝ALT异常组与ALT正常组比较,脂联素水平下降.结论 非酒精性脂肪肝存在不同程度胰岛素抵抗,脂联素水平降低;合并代谢综合征者胰岛素抵抗更为严重,脂联素水平更低;合并ALT异常时脂联素水平下降     

Physical performance is associated with markers of vascular inflammation in patients with coronary heart disease.

BACKGROUND: Coronary heart disease as well as major cardiovascular risk factors are associated with elevated levels of pro-inflammatory markers. There is, however, limited information about how changes in lifestyle improving the cardiovascular risk profile influence these levels. The aim of the study was to evaluate whether changes in lifestyle measures with special attention to physical activity, were associated with the levels of such markers. DESIGN: Coronary heart disease patients (n = 197) were randomized to either a comprehensive lifestyle intervention programme comprising regular physical activity, low fat diet and smoking cessation, or usual care with routine follow-up in the outpatient clinic for 6 months. An exercise test and fasting blood samples analysed for soluble cell adhesion molecules, C reactive protein and pro-inflammatory cytokines were evaluated before and at the end of the study. RESULTS: Improved diet, physical performance and reduction in smoking were obtained in the intervention programme when compared with usual care patients, but no significant group differences in levels of inflammatory markers were observed. In the total population, however, physical performance significantly and inversely predicted levels of soluble cell adhesion molecule 1, (P < 0.001), C-reactive protein (P < 0.001) and interleukin-6 (P = 0.01) at 6 months. Smokers had elevated levels of soluble cell adhesion molecule 1 when compared with non-smokers (P = 0.011). CONCLUSIONS: We demonstrated that physical performance is inversely correlated with levels of pro-inflammatory markers in coronary heart disease patients, possibly retarding the process of atherosclerosis. No effect on inflammatory markers was obtained with a 6-month lifestyle intervention programme when compared with patients who received usual care follow-up.     

伴有代谢综合征的冠心病患者高敏C反应蛋白浓度的变化

目的探讨伴有代谢综合征(MS)的冠心病患者血清中高敏C反应蛋白(hs-CRP)浓度的变化及其临床意义。方法选择179例冠心病患者为冠心病组,根据冠心病组患者是否伴有MS分为2个亚组,伴MS组(63例)和不伴MS组(116例)。同期选择健康体检者80例为正常对照组。测量身高、体重、血压,测定血糖、血脂和hs-CRP等相关指标,分析血清hs-CRP浓度与冠心病、MS的关系。结果冠心病组患者血清hs-CRP(1.77±0.96)mg/L较正常对照组(1.43±0.51)mg/L明显增高(P<0.05)。伴MS组血清hs-CRP(3.06±1.14)mg/L明显高于正常对照组,且差异有统计学意义(P<0.01);而不伴MS组血清hs-CRP(1.52±0.75)mg/L较正常对照组虽有增高,但差异无统计学意义(P>0.05)。血清hs-CRP浓度随着MS组分数目的增加而增高,且差异有统计学意义(P<0.05)。相关分析表明,血清hs-CRP与体重指数、收缩压、舒张压、TC、空腹血糖呈正相关(r=0.355,0.218,0.312,0.368,0.297,P<0.05),与HDL-C呈负相关(r=-0.221,P<0.05)。结论冠心病患者血清hs-CRP浓度增高,尤其以伴有MS的冠心病患者增高明显。     

小肠型脂肪酸结合蛋白基因多态性与老年冠心病人群发病风险的研究

目的研究老年人群小肠型脂肪酸结合蛋白(I-FABP)基因编码区外显子2中第54位密码子多态性与冠心病患者血脂水平和冠心病发病风险的关系。方法随机选取老年冠心病患者56例作为病例组,同时选取我院体检中心的健康老年人49例作为对照组,记录一般临床资料,检测TC、TG、LDL-C、HDL-C水平,同时采用聚合酶链反应技术、DNA限制性内切酶酶切技术检测该人群的I-FABP基因HhaⅠ酶切位点的多态性。结果所有受试者I-FABP基因编码区外显子第54位密码子存在HhaⅠ酶切位点,产生多态性片段为野生型A/A、杂合突变型A/T、纯合突变型T/T。病例组A/T、T/T基因携带者TC、TG、LDL-C水平明显高于A/A携带者,差异有统计学意义(P<0.05)。对照组A/A基因携带者与A/T、T/T基因携带者TC、TG、LDL-C、HDL-C差异无统计学意义(P>0.05)。体质量指数、饮食习惯、I-FABP等位基因是冠心病主要的独立危险因素。结论样本人群中存在I-FABP基因多态性;I-FABP基因多态性影响老年冠心病患者的脂质代谢水平,与老年人冠心病发病风险有关,可能是冠心病发生的遗传易感因素。     

Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers

Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFAs) in the adipocytes during lipolysis. Serum FFA relates to metabolic syndrome, and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test. Insulin resistance was determined using frequently sampled intravenous glucose tolerance test. Serum lipids and inflammation markers were measured at fasting. During oral glucose tolerance test, serum FABP4 decreased by 40%, reaching its nadir at 3 hours (from 45.3 ± 3.1 to 31.9 ± 1.6 ng/mL), and stayed below the baseline at 5 hours (35.9 ± 2.2 ng/mL) (P < .0001 for both, compared with the baseline). Serum FFA decreased by 10-fold, reaching a nadir at 2 hours (from 0.611 ± 0.033 to 0.067 ± 0.004 mmol/L), then rebounded to 0.816 ± 0.035 mmol/L at 5 hours (P < .001 for both, compared with baseline). Both fasting FABP4 and nadir FABP4 correlated with obesity. Nadir FABP4 correlated also with insulin resistance parameters from frequently sampled intravenous glucose tolerance test and with inflammation. Nadir FFA, but not fasting FFA, correlated with the metabolic syndrome parameters. In conclusion, fasting FABP4 related to metabolic risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured after glucose loading may provide better risk assessment than the fasting values.     

冠状动脉病变与代谢综合征及高敏C反应蛋白关系的探讨

目的 探讨冠状动脉病变与代谢综合征、血清高敏C反应蛋白（hs—CRP）水平之间的关系。方法 对2003年4月至2004年4月期间北京协和医院就诊的227例临床怀疑冠心病的患者进行冠状动脉造影,将其中冠状动脉狭窄大于50％的170例患者按照中国代谢综合征诊断标准分为代谢综合征组和非代谢综合征组。对两组同时进行hs—CRP水平的测定。两组的冠状动脉造影和hs—CRP结果进行组内及组间统计学分析。结果 不同hs—CRP水平下冠状动脉病变类型的比较表明,随着hs—CRP水平的升高,代谢综合征组的冠状动脉病变严重程度加重,差异有统计学意义,特别是在hs-CRP〉3．5μg／ml时,这种差异尤其明显。结论 hs—CRP可以作为预测代谢综合征合并冠状动脉粥样硬化性心脏病患者冠状动脉病变严重程度的预测指标。     

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Aims/hypothesis Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. Methods Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. Results RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA_1c in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. Conclusions/interpretation RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.     

老年冠心病合并代谢综合征患者平均血小板体积的相关性研究

目的研究合并代谢综合征(MS)老年冠心病患者的平均血小板体积(MPV)变化及相关影响因素。方法选择冠状动脉造影确诊的老年冠心病患者288例,根据诊断分为MS组154例和非MS组134例。测定入院时MPV、脂联素、高敏C反应蛋白(hs-CRP)等指标,并进行相关性分析。结果与非MS组比较,MS组MPV和血小板分布宽度显著升高,差异有统计学意义(P<0.05,P<0.01);相关性分析显示,MS组患者MPV与体质量指数、空腹胰岛素、胰岛素抵抗指数(HOMA-RI)、hs-CRP和冠状动脉病变积分呈正相关(P<0.05,P<0.01),与HDL-C和脂联素呈负相关(P<0.01);多重线性回归分析显示,MS组MPV与hs-CRP、HOMA-RI显著独立正相关,与脂联素和HDL-C显著独立负相关(P<0.05)。结论合并MS的老年冠心病患者MPV显著升高,与hs-CRP、HOMA-RI、脂联素及HDL-C有密切关系。     

Chemerin is associated with inflammatory markers and metabolic syndrome phenotypes in hypertension patients

Background: Chemerin is a new adipokine elevated in states of obesity and metabolic syndrome. In order to identify the role of chemerin in hypertension, we conducted a case--control study to evaluate the role of chemerin in hypertension.

Methods: Two hundred and thirty-seven new-diagnosed essential hypertensive (EH) patients and one hundred and ten normotensive healthy subjects (NT) were enrolled. After an overnight fasting, participants underwent an oral glucose-tolerance test (OGTT). Anthropometric measurements and serum analyses were checked, including body mass index (BMI), waist circumference, insulin, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, glucose, chemerin, hs-CRP, TNF-α and IL-6.

Results: Compared with healthy controls, subjects with hypertension had significantly higher chemerin serum levels (p?p?p?=?0.289).

Conclusions: Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome in hypertensive subjects and was independently associated with hypertension after adjustment for age, gender and metabolic risk factors.     

Serum adipocyte fatty acid-binding protein is independently associated with complex coronary lesions in patients with stable coronary artery disease

The association between circulating adipocyte fatty acid-binding protein (A-FABP) levels and coronary artery disease (CAD) is reported. We assessed whether plasma A-FABP levels are associated with angiographic coronary lesion morphology in patients with stable CAD. Serum A-FABP levels were analyzed in 115 patients with stable CAD (mean age 69 ± 10 years; 80 % men). These patients were angiographically studied and divided into two groups: simple lesions (n = 34) and complex lesions (n = 81). We also compared 50 age- and gender-matched controls with no evidence of CAD. Serum A-FABP levels in patients with stable CAD were significantly higher than those in controls. In patients with stable CAD, serum A-FABP levels were significantly higher in patients with complex lesions than in those with simple lesions: median (25th–75th percentile), 23.4 (17.7–30.8) vs 18.2 (12.2–24.7) ng/ml, P < 0.01. Serum A-FABP levels were also significantly associated with angiographic scores of extent of coronary lesion (r = 0.21, P = 0.02). Multiple logistic analysis that included dyslipidemia, statin therapy, and extent score demonstrated that serum A-FABP was independently associated with complex lesions. The multiple adjusted odds ratio for a complex lesion with a serum A-FABP level (per doubling) was 2.38 (95 % confidence interval, 1.03–6.41; P = 0.03). High serum A-FABP levels were significantly associated with complex coronary lesions in patients with stable CAD, suggesting that high A-FABP levels may be involved in coronary plaque vulnerability.