【作者】 周密；

【导师】 包玉倩；

【作者基本信息】 苏州大学 ， 内科学， 2010， 硕士

【摘要】 目的1.探讨男性血清骨钙素水平与代谢综合征及组分的关系。2.研究骨钙素与冠状动脉粥样硬化病变程度的关系。方法1.选择2008.7—2009.10上海交通大学附属第六人民医院心内科入院行冠状动脉造影检查(Coronary angiography, CAG)的男性受试者187例作为研究对象,平均年龄64.9±10.7岁。测量简易体脂参数,包括体重、腰围(W)、体重指数(BMI),测定空腹血糖(FPG)、餐后2h血糖(2hPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1c)、糖化血清白蛋白(GA)、空腹胰岛素(FINS)、碱性磷酸酶(ALP)、骨钙素和脂联素水平。以稳态模式评估法的胰岛素抵抗指数(HOMA-IR)评价患者的胰岛素敏感性,以稳态模式评估法的β细胞功能指数(HOMA-%B)评价基础胰岛素分泌功能。将受试者按照是否存在代谢综合征(MS)分为MS组与非MS(Non-MS)组,比较两组间临床特征及血清骨钙素水平,分析MS组分数增加与骨钙素水平的变化趋势。探讨血清骨钙素水平与糖、脂代谢等临床生化指标的相关性,并进一步分析骨钙素与MS的关联。2.在上述受试者中进一步探讨血清骨钙素水平与冠脉病变程度的关系,并对其中60例正常糖耐量(NGT)者进行亚组分析,其中包括冠状动脉粥样硬化性心脏病(冠心病,CAD)患者48例(稳定型心绞痛20例,不稳定型心绞痛28例),非冠心病(Non-CAD)受试者12例。根据CAG结果采用冠状动脉粥样硬化指数(CAI)对主要冠状动脉内径的狭窄程度进行定量评定,比较CAD与Non-CAD组血清骨钙素水平,分析病变血管数目与血清骨钙素水平的关系,及血清骨钙素与CAI的相关性。结果1. MS组较Non-MS组BMI、W、血压(BP)、FPG、FINS、HbA1c、GA、TG及HOMA-IR明显升高(P<0.05-0.001)。而HDL-C、脂联素及骨钙素水平在MS组显著降低(P值均<0.001)。年龄、TC、LDL-C、HOMA-%B、ALP及吸烟史的比例在两组间没有明显差异(P>0.05)。2.在所有受试者血清骨钙素水平波动于5.34-53.67ng/mL。MS组血清骨钙素水平明显低于Non-MS组[5.61ng/mL(11.93- 20.56) vs. 17.95ng/mL(15.12-24.44),P<0.001]。进一步按照MS的组分数分组后发现:同1-2项代谢异常组相比[21.21ng/mL(16.08-26.47)],3项[16.93ng/mL(12.00-24.11)]、4项[15.36ng/mL(12.81-18.01)]及5项代谢异常组[14.74ng/mL ( 10.78-18.64 ) ]血清骨钙素水平显著降低(P<0.05-0.001),5项代谢异常组血清骨钙素水平也显著低于3项代谢异常组(P<0.05)。将血清骨钙素值按三分位点分层后分析可见,随着骨钙素水平的上升,MS发生频率及除高血压外MS各组分的患病率均显著降低(P<0.05-0.001)。3.简单相关分析显示:血清骨钙素水平与BMI(r=-0.185,P=0.015)、W(r=-0.310,P<0.001)、FPG(r=-0.318,P<0.001)、HbA1c(r=-0.211,P=0.006)及HOMA-IR(r=-0.181,P=0.017)呈负相关,与LDL-C(r=0.172,P=0.025)及ALP(r=0.279,P<0.001)呈正相关。进一步校正年龄和BMI后发现,血清骨钙素水平与W、FPG、HbA1c、HOMA-IR及ALP的相关关系依然明显,此外,还与HOMA-%B(r=0.182,P=0.022)呈显著正相关。多元逐步回归分析显示W和高血糖是血清骨钙素水平的独立影响因素。除W、HbA1c与HOMA-IR独立相关外,血清骨钙素水平也是HOMA-IR的独立影响因素。4.以MS为应变量进行多元Logistic回归分析,结果显示BMI、HOMA-IR、HbA1c及血清骨钙素水平是MS的独立影响因素,且骨钙素水平位于上1/3位点者较下1/3位点者及中1/3位点者有显著低的发生MS的风险(OR值分别为0.216和0.401)。5.按照CAG结果,将受试者分为冠心病(CAD)组和非冠心病组(Non-CAD)。CAD组年龄、HbA1c显著高于Non-CAD组(P<0.05),而骨钙素等指标在两组间无显著差异。在CAD患者,除高血压外MS各组分的患病率均随血清骨钙素水平的升高而下降(P<0.05-0.001),但冠脉病变支数及狭窄程度无明显差异。进一步对60例NGT受试者进行亚组分析后显示:血清骨钙素水平在CAD组显著低于Non-CAD组[20.52ng/mL (16.53-25.33) vs. 24.04ng/mL (17.58-33.64),P<0.05],而其他临床指标在两组间无明显差异。将受试者按照血管病变数进行分组后显示,随病变血管数目的增加,骨钙素水平呈逐渐降低趋势,同0支病变组相比,多支病变组血清骨钙素水平显著降低(P<0.05)。6.简单相关分析显示血清骨钙素水平与CAI呈显著负相关(r=-0.440,P=0.003)。以CAI为应变量进行多元逐步回归分析显示血清骨钙素是CAI的独立影响因素(β=-0.868,P=0.003)。结论1.血清骨钙素与糖脂代谢相关,MS组份的数目随着血清骨钙素水平增高而减少;血清骨钙素水平升高的个体,MS的患病风险明显降低。2.在CAD人群中,血清骨钙素水平相对低的个体其MS及除高血压外的MS各组分的发生频率显著升高。3.糖耐量正常的受试者中,冠脉病变程度相对重的个体其血清骨钙素水平较低。血清骨钙素水平是冠脉病变程度的独立影响因素。更多还原

【Abstract】 Objectives1. To investigate the relationship of serum osteocalcin with metabolic syndrome and its components in men.2. To explore the association of serum osteocalcin with the severity of coronary atherosclerosis.Methods1. We recruited 187 men who were admitted to the Department of Cardiology of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital to undergo coronary angiography (CAG) between July 2008 and October 2009, their mean age was 64.94±10.66 years. Anthropometric parameters including weight, waist circumference (W) and body mass index (BMI) was measured and biochemical parameters including fasting plasma glucose (FPG), 2-h post-load plasma glucose (2hPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), glycated hemoglobin A1c (HbA1c), glycated albumin (GA), fasting insulin (FINS), alkaline phosphatase (ALP), serum osteocalcin and adiponectin were analyzed. Insulin sensitivity and insulin secretion were estimated by homeostasis model assessment-insulin resistance (HOMA-IR) and homeostasis model assessment of beta cell function (HOMA-%B). Serum osteocalcin concentrations were compared between metabolic syndrome (MS) group and non-metabolic syndrome (Non-MS) group. The changing of serum osteocalcin along with the increasing of the components of MS was analyzed. In addition, multiple stepwise regression analysis was used to determine the association of serum osteocalcin with parameters related to glucose metabolism, fat metabolism and lipid profile, and multiple logistic regression analysis was used to determine the influence of serum osteocalcin on MS. 2. We further investigated the association of serum osteocalcin with the severity of coronary atherosclerosis. A subgroup analysis was performed in 60 subjects with normal glucose tolerance (NGT) from the above population. They were divided into coronary artery disease (CAD) group (n=48) and non-coronary artery disease (Non-CAD) group (n=12). The severity of CAD was accessed by the coronary atherosclerosis index (CAI). Serum osteocalcin concentrations were compared between CAD group and Non-CAD group. The differences of serum osteocalcin concentrations were further compared among subjects with different number of vessel lesions. Moreover, the relationship between serum osteocalcin and CAI was also analyzed.Results1. Compared with Non-MS group, subjects in MS group had significantly higher BMI, W, blood pressure (BP), FPG, FINS, HbA1c、GA、TG and HOMA-IR (P<0.05). However, age, TC、LDL-C、HOMA-%B、ALP and percentage of subjects with a cigarette history were not different between the two groups (P>0.05).2. Serum osteocalcin concentrations ranged from 5.34 ng/mL to 53.67 ng/mL. As compared with Non-MS group, serum osteocalcin concentrations were significantly lower in MS group. When subjects were further divided into different groups according to the components of metabolic disorders, serum osteocalcin concentrations were decreased with the incement of the components of metabolic disorders. Significant lower serum osteocalcin concentrations were found in 3, 4 and 5 components metabolic disorder group compared with 1-2 components metabolic disorder group (P<0.05-0.001), and similar difference was found in subjects with 5 components compared with those with 3 components (P<0.05). The frequency of MS and its components except for hypertension were decreased with the increment of serum osteocalcin after stratified by tertile (P<0.05-0.001).3. In whole participants the correlation analysis showed that serum osteocalcin was inversely correlated with BMI (r=-0.185, P=0.015), W (r=-0.310, P<0.001), FPG (r=-0.318, P<0.001), HbA1c (r=-0.211, P=0.006) and HOMA-IR (r=-0.181, P=0.017), and positively correlated with LDL-C (r=0.172, P=0.025) and ALP (r=0.279, P<0.001). After further adjusted for age and BMI, serum osteocalcin was still negatively correlated with W, FPG, HbA1c and HOMA-IR, and positively correlated with HOMA-%B (r=0.182, P=0.022) and ALP (r=0.290, P<0.001). Multivariate stepwise regression analysis showed that W and hyperglycemia were independent factors significantly influencing serum osteocalcin. Moreover, serum osteocalcin was an independent factor for HOMA-IR.4. Multiple logistic regression analysis was performed using the presence of MS as a dependent variable. As a result, BMI, HOMA-IR, HbA1c and serum osteocalcin were independent predictors for the development of MS. Subjects with the highest tertile of serum osteocalcin had an increased risk of developing MS compared with those with osteocalcin in the middle and lowest tertile (OR, 0.216 and 0.401).5. Total subjects were divided into CAD group and Non-CAD group according to CAG. Age and HbA1c were significantly higher in CAD group, however, osteocalcin was not significantly different between the two groups. In CAD patients, the frequency of MS and its components except for hypertension were decreased with the increment of serum osteocalcin (P<0.05-0.001), however, the severity of CAD showed no significant difference.Subgroup analysis in 60 subjects with NGT showed that age, BP, parameters related to glucose, fat and lipid metabolism, FINS, HOMA-IR, HOMA-%B, ALP and adiponectin had no significant differences between CAD group and Non-CAD group, while serum osteocalcin concentrations were significantly lower in Non-CAD group compared with CAD group [20.52ng/mL (16.53-25.33), p<0.05 vs. 24.04ng/mL (17.58-33.64)]. As compared with 0 vessel disease group, multiple vessels disease group had significantly lower serum osteocalcin concentrations (P<0.05).6. Serum osteocalcin was significantly correlated with CAI (r=-0.440, P=0.003). Multivariate stepwise regression analysis showed that serum osteocalcin was the independent factor significantly influencing CAI (β=-0.868, P=0.003).Conclusions1. Serum osteocalcin was important for glucose and fat metabolism. The risk of MS and the number of its components were decreased with the increment of serum osteocalcin.2. In CAD patients, the frequency of MS and its components except for hypertension increased with the decreasing of serum osteocalcin. 3. In NGT subjects, serum osteocalcin concentrations decreased with the aggravating of coronary atherosclerosis. Osteocalcin was the only independent factor significantly influencing CAI.更多还原