葡萄糖激酶基因启动子G/A变异与空腹高血糖相关

目的　研究葡萄糖激酶 (GCK)基因启动子 - 30G/A变异在中国南方地区汉族人群中的分布并比较其在正常糖耐量 (NGT)者及糖耐量低减 (IGT)者中的差别及其与糖代谢相关指标之间的关系。方法　研究对象为 4 4 4例无糖尿病及亲缘关系的中国南方地区汉族人 ,其中 2 2 2例为NGT ,2 2 2例为IGT。通过PCR RFLP检测GCK启动子 - 30位置的G→A变异所导致BsiHKAⅠ酶切位点的缺失。结果　在IGT及NGT的人群中含有A等位基因的频率分别为 18.2 %及 19.8%。与GG基因型的人群相比 ,带有A等位基因的人群空腹血糖显著增高〔(5 .35± 0 .5 9vs 5 .19± 0 .5 3)mmol/L ,P =0 .0 0 6〕 ,在IGT的人群中 ,带有A等位基因的人群空腹血糖仍显著增高〔(5 .5 4± 0 .5 8vs 5 .35± 0 .5 2 )mmol/L ,P =0 .0 2〕 ,而在NGT的人群中 ,不同GCK基因型者的空腹血糖差异无显著性。结论GCK基因启动子 - 30G/A变异与空腹高血糖水平相关 ,可能对中国人的IGT有一定的影响。     

空腹血糖与冠状动脉病变程度的相关性

目的探讨空腹血糖（FPG）水平与冠状动脉（下称冠脉）病变程度的相关性。方法回顾分析913例高度怀疑冠心病（CHD）而行冠脉造影的患者的临床资料,冠脉造影病变程度由是否诊断CHD、冠脉病变支数和冠脉病变Gensini总积分三方面表示。对FPG水平与冠脉病变程度进行单因素和多因素分析。结果FPG与冠脉病变程度密切相关：（1）Logistic回归结果显示FPG与冠脉有无病变显著相关（OR值1.462,95%CI为1.178~1.813,P〈0.01）;（2）多元逐步回归结果显示在校正了年龄、性别等因素之后,FPG与冠脉病变支数（r=0.164,P〈0.01）、冠脉病变总积分（r=0.088,P〈0.05）仍然独立相关。随着FPG的升高,冠脉病变支数增加。结论冠心病高危人群的FPG水平与冠脉病变程度密切相关,即使在糖尿病前期,随着FPG升高,冠脉病变程度也更加严重。     

Increased fasting plasma insulin concentrations are associated with the severity of angiographic coronary artery disease

Fasting plasma insulin concentrations were obtained in 82 patients (51 men and 31 women), mean age 60 +/- 11 years, with a body mass index >25 kg/m(2) who had coronary angiography because of suspected symptomatic coronary artery disease (CAD). Obstructive CAD was diagnosed if there was >50% obstruction of > or =1 vessel. Of 82 patients, 37 (45%) had left main or 3-vessel CAD, 22 (27%) had 2-vessel CAD, 9 (11%) had 1-vessel CAD, and 14 (17%) had no obstructive CAD. Among the 4 groups, there was no significant difference in gender, age, dyslipidemia, and smoking. Hypertension (p = 0.0003), diabetes mellitus (p = 0.035), and increased fasting plasma insulin concentration (p < 0.0001) were significantly associated with the severity of CAD. Stepwise ordinal logistic regression analysis identified increased fasting plasma insulin concentrations in these obese subjects as a significant independent risk factor for the severity of angiographic CAD (p < 0.0001).     

Terminal ileum resection is associated with higher plasma homocysteine levels in Crohn's disease

BACKGROUND: Elevated plasma total homocysteine (tHcy) is associated with a higher risk of thrombosis. Crohn's disease (CD) is associated with hypercoagulability of undefined etiology. We investigated tHcy in patients with CD and its relationship with vitamin status, disease activity, location, duration, and history of terminal ileum (TI) resection. STUDY: We examined fasting plasma tHcy, folate, serum vitamin B12 levels, and sedimentation rate in consecutive adult patients with CD. Harvey-Bradshaw index of CD activity and history of TI resection and thromboembolism were recorded. RESULTS: Median plasma tHcy was 10.2 micromol/L in 125 patients with CD. Men (n = 60) had higher plasma tHcy than women (n = 65) (11.2 vs. 9.1 micromol/L; p = 0.004). Patients with a history of TI resection showed lower serum B12 levels (293 vs. 503 pg/mL; p < 0.001) and higher plasma tHcy levels (11.0 vs. 9.35 micromol/L; p = 0.027) than patients without such history. Multivariate analysis showed history of TI resection, serum B12, and creatinine levels to be significant predictors of elevated plasma tHcy. Fourteen patients with CD with a history of thrombosis had an elevated median plasma tHcy of 11.6 micromol/L. CONCLUSIONS: Terminal ileum resection contributes to elevated plasma tHcy levels in CD cases. We recommend tHcy screening in patients with CD, especially in those with prior history of TI resection, and the initiation of vitamin supplementation when appropriate.     

空腹血糖及糖尿病与冠状动脉病变程度的相关性

目的 探讨空腹血糖及糖尿病与冠状动脉病变程度的相关性.方法 回顾分析419例拟诊为冠心病并行冠状动脉造影的患者的临床资料,采用Gensini积分系统对冠状动脉病变程度进行评估.采用Logistic回归分析空腹血糖及糖尿病与冠脉病变总积分的相关性.结果 Logistic回归分析发现糖尿病与冠脉病变积分显著相关,但根据Gensini积分四分位分组,空腹血糖并没有是随着冠脉病变程度的加重而升高.结论 冠脉病变可能与糖尿病疾病显著相关,但与空腹血糖水平关系不大.因此,对糖尿病的治疗在于全面控制各危险因素,而不是单纯的控制血糖.     

Decreased plasma CXCL16/SR-PSOX concentration is associated with coronary artery disease

OBJECTIVES: To investigate for the first time whether the plasma CXCL16 concentration is altered in coronary artery disease (CAD) patients. BACKGROUND: Accumulating evidence suggests that the novel chemokine/scavenger receptor CXCL16/SR-PSOX is involved in the development of atherosclerosis and CAD. METHODS: Using ELISA we assessed the plasma CXCL16 concentration in 40 stable angina pectoris (SAP) patients, 17 unstable angina pectoris/non-ST-elevation myocardial infarction (UAP/non-STEMI) patients, 387 survivors of a first myocardial infarction (MI) and healthy control subjects (44 controls for SAP and UAP/non-STEMI patient groups and 387 controls for post-MI patients). RESULTS: SAP patients exhibited significantly lower median CXCL16 levels (2111 pg/ml) than the corresponding control subjects (2678 pg/ml) (P=0.0012). UAP/non-STEMI patients also appeared to have lower CXCL16 levels (2192 pg/ml) compared with controls (NS). Patients investigated 3 months after MI tended (P=0.07) to have lower CXCL16 levels (2529 pg/ml) than the corresponding controls (2638 pg/ml). There were no significant correlations between CXCL16 levels and different measures of CAD severity determined by quantitative coronary angiography in post-MI patients. Neither patients nor controls exhibited significant correlations between CXCL16 levels and plasma lipoprotein fractions, inflammatory cytokines, C-reactive protein or numbers of inflammatory cells in peripheral blood. CONCLUSIONS: The finding that lower plasma CXCL16 concentration is associated with CAD might indicate a potential atheroprotective function of CXCL16.     

不同年龄患者空腹血糖与冠脉病变的相关性

目的:探讨不同年龄患者空腹血糖(FPG)与冠脉病变之间的相关性. 方法:回顾性分析拟诊冠心病行冠脉造影的患者580例,按FPG水平分为3组,对患者临床及冠脉造影资料进行分析. 结果:随着FPG增加,病变部位的比例、病变支数、狭窄程度、病变积分及支架数均增加.年龄＜60岁的患者,空腹血糖受损(IFG)组及糖尿病(DM)组的冠脉病变均重于正常空腹血糖(NFG)组;年龄60～74岁的患者,DM组的冠脉病变较NFG组严重;而年龄≥75岁的患者,FPG并不为冠心病的独立危险因素.结论:冠脉的病变程度随着FPG增加而增加;＜60岁的患者FPG＞5.6 mmol/L或60～74岁的患者FPG＞7.0 mmol/L,其冠脉的病变程度较同龄正常FPG组严重.     

Carotid artery intima-media thickness is associated with coronary artery disease

OBJECTIVE: The intima-media thickness (IMT) of the carotid artery is dependent on the risk factor load during life and correlates well with the degree of atherosclerosis, also in other vascular beds. METHODS: We reviewed our database of IMT measurements, from January 2002 to February 2007. We compared the mean IMT values of patients without a history of coronary artery disease (group 1) with those with a history of coronary artery disease (group 2). For both groups we divided the results of measurements according to age. We compared the IMT between both groups and looked for a correlation with increasing age. The IMT was measured with high-resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. RESULTS: The database contained 598 IMT measurements in group 1 and 672 in group 2. In both groups we observed a significant increase in IMT with increasing age. Within a certain age group, a significant difference in IMT between group 1 and 2 occurred at an age of 40 years or above (age 40-65: IMT 645.54 versus 671.71 microm, respectively, P = 0.04, and age > 65 years: IMT 715.2 versus 772.91 microm, respectively, P = 0.01). CONCLUSIONS: IMT increases with age and is higher in patients with a history of vascular disease. This difference is significant in patients of 40 years or older. This finding supports the recommendations of the prevention conference of the American Heart Association, that carefully performed IMT measurement can add incremental information to traditional risk factor assessment in asymptomatic individuals above the age of 45 years.     

Insulin response to oral glucose load is associated with coronary artery disease in subjects with normal glucose tolerance

AIM: The critical role of hyperinsulinemia, independent of hyperglycemia, in the pathogenesis of atherosclerosis has not been fully determined. We investigated the association between secretion patterns of insulin after oral glucose load and the severity of coronary artery disease (CAD) in patients with normal glucose tolerance (NGT). METHODS: We enrolled 116 subjects with NGT from 243 patients who had undergone coronary angiography and a standard 75-g oral glucose tolerance test. The patients were divided into 0-vessel, single-vessel and multi-vessel disease groups on the basis of the severity of CAD. RESULTS: The 2-h insulin levels in the multi-vessel disease group (p=0.005) and the single-vessel disease group (p<0.05) were significantly higher than those in the 0-vessel disease group. Multivariate analysis revealed that the levels of 2-h insulin were an independent variable for the presence of CAD (p=0.02) after adjustment for gender and the presence of each criterion of metabolic syndrome using the definition of the International Diabetes Federation. CONCLUSION: A slight but significant increase in prolonged insulin secretion, which is associated with the early stage of insulin resistance, in subjects with NGT, may play an important role in the pathogenesis of atherosclerosis.     

Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease

Reduced incidence of type-2 diabetes has been shown in patients treated with pravastatin. Adiponectin can exhibit beneficial effects on glucose metabolism. We investigated whether pravastatin could improve glucose tolerance associated with increasing adiponectin levels in patients with impaired glucose tolerance (IGT). This study consisted of 40 coronary artery disease (CAD) patients with IGT assessed by oral glucose tolerance test (OGTT). Patients were randomized to receive pravastatin (n=20) or no lipid-lowering medications (control group, n=20) for 6 months, after which OGTT was repeated and adiponectin levels were measured. Pravastatin treatment significantly decreased levels of total cholesterol (16%), low-density lipoprotein cholesterol (23%) and high-sensitivity C-reactive protein (37%) (p<0.01, respectively). At 2h in OGTT, pravastatin significantly improved hyperglycemia (-14%) and hyperinsulinemia (-23%). Pravastatin treatment significantly elevated plasma adiponectin levels (35%; p<0.001) but not in the control group. The glucose reduction at 2h post-OGTT was significantly associated with increased levels of adiponectin (r=-0.462; p=0.003). Pravastatin treatment is an independent predictor for improvement of post-loaded hyperglycemia (odds ratio; 5.7; 95% confidence interval 1.7-19.3; p=0.003) and achieved beneficial conversion from IGT to normal glucose tolerance (40%; p=0.03). Pravastatin exhibits beneficial effects on glucose metabolism especially in the postprandial state associated with increasing plasma adiponectin levels in CAD patients with IGT.     

Hypoadiponectinemia is associated with impaired glucose tolerance and coronary artery disease in non-diabetic men.

BACKGROUND: Impaired glucose tolerance (IGT) is a significant risk factor for cardiovascular disease, but is not always recognized in the clinical setting. An anti-atherogenic adipocytokine, adiponectin, is decreased in type 2 diabetes mellitus, but its role in non-diabetic subjects has not been clarified. The hypothesis investigated in the present study was that plasma adiponectin levels correlate with IGT and coronary artery disease (CAD) in non-diabetic men. METHODS AND RESULTS: Glucose intolerance was evaluated by an oral glucose tolerance test and plasma adiponectin levels were measured in 232 non-diabetic men who underwent coronary angiography. Patients with IGT (n=102) had significantly lower adiponectin levels than those with normal glucose tolerance (n=130) (4.47 [3.23-6.39] vs 5.85 [3.99-8.65] mug/ml, p=0.003). Plasma adiponectin levels were associated with IGT in multiple logistic regression analysis (odds ratio (OR) 0.623, 95% confidence interval (CI) 0.397-0.980; p=0.041). Non-diabetic patients with CAD (n=122) had lower adiponectin levels than those without CAD (n=110) (4.60 [3.32-6.38] vs 6.08 [4.10-9.88] microg/ml, p<0.001). Multiple logistic regression analysis demonstrated adiponectin independently correlated with the presence of CAD (OR 0.432, 95% CI 0.256-0.728; p=0.002). CONCLUSIONS: Hypoadiponectinemia is associated with IGT and CAD in non-diabetic men, suggesting that the adiponectin level can provide valuable information regarding the risk of CAD even in non-diabetic subjects.     

空腹血糖水平与经皮冠状动脉介入治疗五年预后的关系

目的 了解老年冠心病患者经皮冠状动脉介入治疗(PCI)预后及相关危险因素,分析空腹血糖(FPG)水平与PCI术后冠状动脉再狭窄和心脏事件发生率的关系,为论证FPG受损(IFG)诊断标准提供相关心血管终点事件的依据.方法 选取2000年1月至2001年12月于解放军总医院成功接受PCI术的老年冠心病患者共269例,按照基线空腹血糖水平分为4组(组1:FPG<5.6mmol/L;组2:5.6 mmol/L≤FPG<6.1 mmol/L;组3:6.1 mmol/L≤FPG<7.0 mmoL/L;组4:FPG≥7.0mmol/L),随访时间为5年,进行PCI术后再狭窄、复发性心脏事件、生存率及相关危险因素的分析.结果 5年随访结束后5.6 mmol/L≤FPG<6.1 mmol/L人群总心脏事件发生率、再次血运重建率、心绞痛复发率以及再狭窄发生率显著高于FPG<5.6 mmol/L的人群(P均<0.05),而与6.1 mmol/L≤FPG<7.0 mmol/L人群比较差异无统计学意义.5年随访结束组2、3、4的无心脏事件的累积生存率显著低于组1(P均<0.05),组2、3之间差异无统计学意义.logistic回归模型结果 显示,水平是PCI术后再狭窄、心脏事件发生、全因死亡、心绞痛复发的危险因素(P均<0.05).结论 FPG 5.6 mmol/L以上的老年冠心病人群PCI术后5年冠状动脉再狭窄及不良心脏事件发生率已开始显著升高,无心脏事件累积生存率显著降低.因此从改善心血管预后角度看,将IFG的下限调整到5.6 mmol/L具有合理性.     

High hexacosanoic acid levels are associated with coronary artery disease

Aims

Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear.

Method

We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas–liquid chromatography mass spectrometry.

Results

C26:0 levels were significantly higher in the CAD group than in the control group (2.42 ± 0.32 vs. 2.27 ± 0.24 μg/ml, P = 0.01) and positively correlated with BMI (r = 0.23, P = 0.008), triglyceride levels (r = 0.22, P = 0.01), and hypertension (P = 0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P = 0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure.

Conclusion

High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.     

ADIPOR2 variant is associated with higher fasting glucose level in non-diabetic Chinese Han population

A high but normal fasting plasma glucose level in adults is a marker for insulin resistance and future development of type 2 diabetes mellitus. We aimed to investigate whether ADIPOR2 variants are associated with increased fasting plasma glucose (FPG) in non-diabetic Chinese Han subjects who had normal FPG levels. This study included 2038 subjects among the non-diabetic Chinese Han population. The ADIPOR2 polymorphisms were genotyped by the TaqMan method. For the analysis, participants were divided into low-normal FPG group (FPG?<?4.88 mmol/L) and high-normal FPG group (6.1 mmol/L?>?FPG?≥?4.88 mmol/L). We identified five single nucleotide polymorphisms (SNPs) of ADIPOR2 gene: rs10773989, rs2370055, rs9300298, rs10773983, and rs13611594. There was no significant difference in FPG levels between different genotypes of rs10773989, rs2370055, rs9300298, and rs13611594. Our data showed a significant association of rs10773983 with higher FPG levels, fasting insulin levels, and homeostatic model assessment of insulin resistance (HOMA-IR) in A-allele carriers (p =?0.006, p <?0.001, and p <?0.001, respectively). The subjects in high FPG group had higher median fasting insulin level (9.25 vs 8.16 μIU/mL, p =?0.003) and higher HOMA-IR (2.21 vs 1.58, p <?0.001) than those in normal FPG group. Subjects with the A-allele of rs10773983 compared to subjects with G-allele had 1.222-fold higher risk for high-normal FPG (OR?=?1.222, 95%CI?=?1.010–1.478, p =?0.039). Our findings suggest that ADIPOR2 rs10773983 polymorphism may be associated with an increased risk of high-normal FPG among non-diabetic Chinese Han subjects who have normal FPG levels.     

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention

Background

Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain.

Methods

The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG ≥126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 ± 1.2 years.

Results

The average patient age was 62 ± 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM , 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P = .04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG ≥109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P = .002) remained independent predictors of mortality.

Conclusions

Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.