Total antioxidant status and coronary artery calcification in type 1 diabetes

OBJECTIVE: Type 1 diabetes is associated with a high risk of coronary heart disease (CHD), despite the absence of dyslipidemia. Oxidative modification may render LDLs more atherogenic. We aimed to assess antioxidant status in type 1 diabetes and its association with coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS: Total antioxidant status (TAS) of serum was measured using the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25 nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects using electron beam computed tomography. RESULTS: TAS was reduced in type 1 diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P < 0.0001). There were associations between TAS and HbA(1c) (r = -0.43; P = 0.0026) and duration of diabetes (r = -0.35; P = 0.0157). Significant CAC was considered present if the Agatston score was >10. The diabetic subjects with significant CAC were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more likely to have high blood pressure (P = 0.040); had higher total cholesterol concentration (P = 0.039), serum creatinine concentration (P = 0.003), and urinary albumin-to-creatinine ratio (P = 0.022); and had lower serum TAS (P = 0.018) compared with those without significant calcification. In logistic regression with CAC as the dependent variable, TAS was entered as a predictor, and the effects on its predictive value of adding other explanatory variables in bivariate analyses were assessed. The power of TAS to predict CAC was independent of many of the traditional CHD risk factors. Whereas TAS as a predictor was no longer statistically significant when age or duration of diabetes were entered into the model, the odds ratio for a TAS concentration above the median value predicting significant CAC only increased from 0.19 to 0.26 and 0.32, respectively. CONCLUSIONS: TAS is reduced in type 1 diabetes and is associated with the presence of CAC.     

Comparison of coronary artery calcification and some coronary artery calcification risk factors in patients on haemodialysis and in patients with type 2 diabetes

Patients on haemodialysis (HD) and patients with type 2 diabetes are at high-risk for coronary artery calcification (CAC). The coronary artery calcium score (CACS), quantified by computed tomography, cannot be completely explained by traditional cardiovascular disease risk factors. CAC was measured in 45 non-diabetic chronic kidney disease patients on HD and in 45 matched type 2 diabetes patients without diabetic nephropathy. Serum calcium, phosphate, 25-hydroxyvitamin D (25[OH]D), alkaline phosphatase, intact parathyroid hormone (iPTH), fetuin-A, high-sensitivity C-reactive protein (hsCRP), albumin, homocysteine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and femoral neck bone mineral density were also measured. No differences were observed in patient distribution across the CACS risk categories between the two groups. Significant differences were observed in serum calcium, phosphate, 25(OH)D, alkaline phosphatase, iPTH, fetuin-A, hsCRP, homocysteine and triglycerides between the two patient groups. Further research into the diverse, numerous and often interlinked factors that influence CAC in different groups of patients is warranted.     

Reduced coronary artery and abdominal aortic calcification in Hispanics with type 2 diabetes

OBJECTIVE: To compare lifestyle factors, cardiovascular risk factors, and coronary artery calcium (CAC) and abdominal aortic calcium (AAC) levels in Hispanic and non-Hispanic white (NHW) individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We recently demonstrated in a small group of nonreferred, healthy, nondiabetic subjects that CAC was reduced in Hispanics compared with NHWs, despite a worse cardiovascular risk factor profile. In this study, we evaluated whether this ethnic disparity in vascular calcification was present in individuals with type 2 diabetes and in several different arterial beds. Hispanic and NHW subjects (n = 245) with type 2 diabetes were evaluated for cardiovascular risk factors using questionnaires and assays of plasma biomarkers. CAC and AAC were measured by electron-beam computer-assisted tomography. RESULTS: Although Hispanics were slightly younger than NHWs, other standard risk factors and novel cardiovascular risk factors, including plasminogen activator-1 and fibrinogen levels, were similar between the groups. Despite the similar risk factor profile, the prevalence of cardiovascular disease (CVD) and mean and median levels of CAC and AAC were lower in Hispanics. Furthermore, the distribution of these calcium scores differed from that of NHWs (P < 0.05), with significantly fewer Hispanic subjects having high CAC or AAC scores. These differences were not explained by differences in CVD prevalence or any measured lifestyle or risk factor. CONCLUSIONS: Hispanics with type 2 diabetes have reduced CAC and AAC levels compared with NHW subjects, suggesting a reduction in the overall burden of vascular calcification and atherosclerosis. These data are consistent with the notion that Hispanics are protected against the development of CVD.     

Determinants of raised C-reactive protein concentration in type 1 diabetes

As a marker of systemic inflammation, raised C-reactive protein (CRP) concentrations which are still within the normal range have been associated with an increased incidence of coronary heart disease (CHD) in non-diabetic subjects. This study aimed to establish potential determinants of raised CRP concentrations in type 1 diabetic patients. We used a sensitive assay to measure 'low-level' CRP concentrations in 167 type 1 patients (93M, 74F, median age 30 years, range 13-67). Stepwise multivariate analysis was used to relate these CRP levels to known cardiovascular risk factors and demographic data. Only six patients had established CHD (median CRP 3.34 mg/l vs. 0.83 mg/l, p=0.032). In subjects without overt CHD, multivariate analysis showed increases in subject age (p=0.0025), BMI (p=0.001) and HbA(1) (p=0.012) to be associated with a higher CRP concentration, as was female sex (p=0.026) and a history of CHD in a first-degree relative (p=0.018, n=57). The duration of diabetes, current smoking status, presence of microvascular complications, lipid status and presence of hypertension were unrelated. This study suggests that some of the risk factors associated with CHD in type 1 patients are also independently predictive of high CRP concentrations. The reasons for this, and whether intervention would prove useful, require further investigation.     

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

1型糖尿病患者超敏C反应蛋白与微量白蛋白尿发展的关系

目的评估年轻的1型糖尿病患者中超敏C反应蛋白（hsCRP）与微量白蛋白尿进展之间的关系。方法选取49例微量白蛋白尿期的1型糖尿病患者及49例年龄、性别、病程与之相匹配的正常白蛋白尿期的1型糖尿病患者。观察两组糖化血红蛋白（HbA1c）和hsCRP水平以及hsCRP与年龄、病程和体质量指数（BMI）的相关性。结果微量白蛋白尿期的1型糖尿病患者的HbA1c和hsCRP的水平明显高于正常白蛋白尿期的1型糖尿病患者,分别为HbA1c（11.86±1.95）%vs（10.26±1.03）%,hsCRP（1.7±0.5）mg/L vs（1.2±0.4）mg/L（均P〈0.01）。hsCRP与年龄、病程、BMI及HbA1c呈显著正相关（P〈0.05或〈0.01）,而与胰岛素的应用量无相关。多元线性回归分析显示年龄、病程和BMI是hsCRP的独立危险因素。结论在年轻的1型糖尿病患者中随着微量白蛋白尿的出现,hsCRP的水平有明显增加,这是炎症状态的一种反应。显示了微量白蛋白尿与亚临床炎症及内皮功能损伤有关。     

C-reactive protein contributes to the hypercoagulable state in coronary artery disease

OBJECTIVES: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. PATIENTS AND METHODS: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. RESULTS: CRP (5-25 microg mL(-1)) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than non-adherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. CONCLUSIONS: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.     

血清C-反应蛋白与妊娠糖尿病的关系研究

目的探讨血清C-反应蛋白（C-reactive protein,CRP）水平与妊娠糖尿病（gestational diabetes mellitus,GDM）的关系。方法选取2002年6月至2006年6月本院门诊及住院患者经75g葡萄糖耐量试验（OGTT）确诊为妊娠期糖尿病患者（GDM）48例和糖耐量异常妊娠妇女32例,并随机选择同期相匹配的正常糖耐量妊娠妇女80例（作为对照组）,同时检测空腹血清CRP水平。结果GDM组C-反应蛋白水平明显高于另两组（P〈0.05）;CRP水平与孕前体重指数（BMI）、空腹血糖、空腹胰岛素呈正相关,相关系数分别为0.348、0.156和0.296,P值分别为0.0001、0.0178和0.0004。直线回归方程y=0.0741x1＋0.0147x2＋0.0397x3-1.457,r2=0.2469。结论C-反应蛋白与GDM密切相关,参与了其发病机制。     

Increased prevalence of significant coronary artery calcification in patients with diabetes

OBJECTIVE: Coronary artery disease is the major cause of morbidity and mortality in patients with diabetes. Detection of coronary artery disease before the first myocardial infarction and before anginal symptoms will allow for strategies designed to reduce the cardiovascular event rate in this group of patients. Electron beam-computed tomography (EBCT) is a noninvasive technology for evaluating the extent of coronary artery atherosclerosis that relies on the detection of coronary artery calcium (CAC). We used EBCT to detect significant coronary artery atherosclerosis in diabetic patients without symptoms of heart disease. RESEARCH DESIGN AND METHODS: We used EBCT to evaluate calcium in the coronary arteries of 139 consecutive diabetic patients scanned over a 20-month period. The CAC scores in this group were compared with a randomly selected nondiabetic control group and a control group that was selected to match a number of established cardiovascular risk factors. RESULTS: Patients with diabetes had a significant increase in the prevalence of CAC scores > or =400 (25.9%) compared with the randomly selected (7.2%) and matched (14.4%) nondiabetic control groups. Scores in this range have been reported to be highly predictive for abnormal stress myocardial perfusion tomography and subsequent coronary events. CONCLUSIONS: Our results, therefore, indicate a substantial prevalence of significant coronary artery disease in an asymptomatic diabetic patient population compared with nondiabetic control subjects. They also suggest that EBCT may be a useful approach for selecting a group of diabetic subjects who would benefit most from additional evaluation for subclinical coronary artery disease.     

超敏C反应蛋白与初诊2型糖尿病下肢血管病变的相关性研究

目的 探讨超敏C反应蛋白(hsCRP)与初诊2型糖尿病(T2DM)下肢血管病变发生的关系.方法 测定正常对照组(A组)、初诊T2DM患者(B组)、初诊T2DM下肢血管病变患者(C组)的hsCRP水平和踝肱指数(ABI)变化.结果 与ABI正常的A组相比,ABI正常的B组和ABI降低的C组hsCRP、体质量指数、腰臀围比、收缩压、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1 c)显著升高或增加(P＜0.01或P＜0.05)、高密度脂蛋白胆固醇(HDL-C)显著下降(P＜0.05);C组hsCRP(1.10±0.36)vs(0.88±0.36)、LDL-C(4.20±1.09)mmol/L vs(3.25±1.04)mmol/L、HbAlc(10.11± 3.92)%vs(8.10±1.51)%明显高于B组(P＜0.01或P＜0.05),HDL-C明显低于B组(1.24±0.32)mmol/L vs(1.36±0.26)mmol/L(P＜0.05).logisitic回归分析显示,hsCRP是初诊T2DM下肢血管病变独立的危险因子(P=0.029).结论 hsCRP与初诊T2DM的发生相关,升高的hsCRP是促使初诊T2DM并发下肢血管病变的独立危险因素.     

罗格列酮对2型糖尿病合并冠心病患者血清基质金属蛋白酶-9及高敏C-反应蛋白的影响

目的:探讨罗格列酮的抗炎、抗动脉粥样硬化作用及其机制.方法:2型糖尿病合并冠心痛患者60例随机分为罗格列酮治疗组和常规治疗组.采用酶联免疫吸附法测定血清基质金属蛋白酶-9、高敏C-反应蛋白水平,观察罗格列酮治疗前后血清基质金属蛋白酶-9、高敏C-反应蛋白水平变化及与常规治疗组之间变化的差别.结果:治疗2周时的血清基质金属蛋白酶-9、高敏C-反应蛋白水平分别较治疗前水平下降,应用罗格列酮治疗组较常规治疗组下降明显,差异有统计学意义(P<0.05).空腹血糖在2治疗组间差异无统计学意义(P>0.05).罗格列酮治疗12周时的血清基质金属蛋白酶-9、高敏C-反应蛋白较治疗2周时下降,差异有统计学意义(P<0.05).结论:罗格列酮具有抗炎及独立于降糖之外的抗动脉粥样硬化作用,且在一定时期内具有时间依赖性.     

Long-term predictors of coronary artery disease and mortality in type 1 diabetes.

We assessed clinical and biochemical predictors of death and/or cardiovascular disease in 147 type 1 diabetes mellitus (DM) patients followed-up for 14 years. At follow-up, 28 of patients (19%) had died, and 25 patients (18%) had developed or died of coronary artery disease (CAD). At baseline, those who died had significantly higher serum creatinine (p=0.001) and urine albumin/creatinine ratio (p=0.016), greater prevalence of retinopathy (p=0.006), lower serum apolipoprotein A1 (p=0.046), and lower daily insulin dose (p=0.024) than those who survived. CAD patients had a longer duration of diabetes (p<0.001), were older at the onset of diabetes and at presentation (p=0.001), and had higher prevalences of retinopathy (p=0.005) and neuropathy (p=0.016). The CAD group also had higher baseline serum creatinine (p=0.02), lower HDL cholesterol (p=0.004) and apolipoprotein A1 (p=0.007) and higher LDL cholesterol (p=0.028) and apolipoprotein B concentrations (p=0.027). Under logistic regression analysis (adjusted for age and sex), baseline urine albumin/creatinine ratio (p=0.003), presence of retinopathy (p=0.004), serum creatinine (p=0.028), and serum urea (p=0.034) were the most powerful predictors of mortality, while duration of diabetes (p<0.0001), baseline HDL cholesterol (p=0.012), serum creatinine (p=0.02), apolipoprotein B (p=0.038), LDL cholesterol (p=0.039), and systolic blood pressure (p=0.055) were the strongest predictors of CAD. These findings emphasize the role of abnormal lipoprotein metabolism in the development of CAD in type 1 DM. Indicators of renal impairment and the presence of retinopathy seem to be of greater importance in predicting overall mortality.     

C-reactive protein associated with coronary artery disease in Iranian patients with angiographically defined coronary artery disease

INTRODUCTION: Several cross-sectional and cohort studies have reported an association between serum markers of inflammation such as C-reactive protein, and coronary heart disease in Caucasian populations. We aimed to investigate the relationship between levels of serum C-reactive protein (hs-CRP) and the presence of coronary artery disease (CAD) in Iranian patients undergoing coronary angiography. METHODS: Serum hs-CRP, fasting lipid profile and blood glucose levels were measured in 110 patients (61 males and 49 females) undergoing routine coronary angiography. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including post-menopausal status and smoking habit were assessed by questionnaire. RESULTS: Of the 110 subjects undergoing angiography, 74 (67.28%) had significant CAD (CAD+) and 36 (32.72%) were classified as having insignificant CAD (CAD-). Mean age (p<0.01), waist circumference (p<0.01) and LDL (p<0.05) and median values of hs-CRP (p<0.01) and triglycerides (p<0.05) were higher in the patients CAD+ than in the subjects CAD-. The proportion of women who were postmenopausal was also significantly higher in the CAD+ group. Age (p<0.01), waist circumference (p<0.05) and hs-CRP (p<0.05) were significant CAD predictive factors from logistic regression analysis. Serum hs-CRP concentrations were significantly higher in smokers compared to non-smokers (p<0.05), low density lipoprotein (LDL) (r=0.31, p<0.001), and serum triglycerides (r=0.191, p<0.05) correlated with serum hs-CRP. The median value of serum hs-CRP increased with the severity of the disease, but failed to reach statistical significance. CONCLUSION: Serum hs-CRP is an independent predictor of angiographically defined CAD in an Iranian population. Measurement of the serum hs-CRP level may improve risk stratification among patients suspected of having CAD. The strong correlations between serum hs-CRP with LDL and smoking may be due to the putative pro-inflammatory effects of these two parameters. The association with serum triglycerides may be indirect and related to insulin resistance and adiposity.     

Fasting glucose, obesity, and coronary artery calcification in community-based people without diabetes

OBJECTIVE Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population. RESEARCH DESIGN AND METHODS We assessed CAC using multidetector computed tomography in 3,054 Framingham Heart Study participants (mean [SD] age was 50 [10] years, 49% were women, 29% had IFG, and 25% were obese) free from known vascular disease or diabetes. We tested the hypothesis that IFG (5.6-6.9 mmol/L) and obesity (BMI ≥30 kg/m(2)) were independently associated with high CAC (>90th percentile for age and sex) after adjusting for hypertension, lipids, smoking, and medication. RESULTS High CAC was significantly related to IFG in an age- and sex-adjusted model (odds ratio 1.4 [95% CI 1.1-1.7], P = 0.002; referent: normal fasting glucose) and after further adjustment for obesity (1.3 [1.0-1.6], P = 0.045). However, IFG was not associated with high CAC in multivariable-adjusted models before (1.2 [0.9-1.4], P = 0.20) or after adjustment for obesity. Obesity was associated with high CAC in age- and sex-adjusted models (1.6 [1.3-2.0], P < 0.001) and in multivariable models that included IFG (1.4 [1.1-1.7], P = 0.005). Multivariable-adjusted spline regression models suggested nonlinear relationships linking high CAC with BMI (J-shaped), waist circumference (J-shaped), and fasting glucose. CONCLUSIONS In this community-based cohort, CAC was associated with obesity, but not IFG, after adjusting for important confounders. With the increasing worldwide prevalence of obesity and nondiabetic hyperglycemia, these data underscore the importance of obesity in the pathogenesis of CAC.