Serum Osteocalcin In Relation To Metabolic Syndrome And Coronary Atherosclerosis In Chinese Men

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.