Clinical Endocrinology (2015) 83, 429–434
doi: 10.1111/cen.12793
ORIGINAL ARTICLE
Association between serum osteocalcin level and visceral obesity in Chinese postmenopausal women Yuqi Luo*,1, Xiaojing Ma*,1, Yaping Hao*, Yiting Xu*, Qin Xiong*, Junling Tang*, Xiaoping Pan*, Yunfeng Xiao†, Yuqian Bao* and Weiping Jia* *Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus and †Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
Summary Background A low serum osteocalcin level, visceral obesity and postmenopausal status are recognized risk factors for cardiovascular disease. Objective We investigated the relationship between the serum osteocalcin level and visceral fat content in a population of Chinese postmenopausal women. Design and patients In total, 1481 postmenopausal women (mean age standard deviation, 571 48 years) were selected from the Shanghai Obesity Study. Measurements Abdominal fat accumulation was quantified using magnetic resonance imaging. Subjects with a visceral fat area (VFA) of ≥80 cm2 were classified as abdominally obese. The total serum osteocalcin level was measured by electrochemiluminescence immunoassay. Results The median serum osteocalcin level was 2066 lg/l (interquartile range, 1688–2542 lg/l). The overall prevalence of abdominal obesity was 491% (n = 727). Abdominally obese subjects had lower serum osteocalcin levels than did nonabdominally obese subjects [1914 (1602–2382) vs 2197 (1814– 2677) lg/l, respectively; P < 0001]. Partial correlation analysis showed that the serum osteocalcin level was still negatively correlated with VFA after adjusting for age, years since menopause and body mass index (P < 001). Moreover, VFA was independently associated with the serum osteocalcin level after adjustment for confounding factors (P < 005). A low serum osteocalcin level was an independent risk factor for abdominal obesity (odds ratio, 0972; 95% confidence interval, 0953– 0991; P = 0004).
Correspondence: Prof. Yuqian Bao, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Tel.: 86 21 64369181; Fax: 86 21 64368031; E-mail: [email protected] 1
These two authors contributed equally to this work.
© 2015 John Wiley & Sons Ltd
Conclusion The serum osteocalcin level was inversely correlated with the visceral fat content in these Chinese postmenopausal women. (Received 18 December 2014; returned for revision 3 January 2015; finally revised 16 March 2015; accepted 9 April 2015)
Introduction Osteocalcin, an osteoblast-specific protein, is a marker of osteogenesis and bone turnover. Evidence from human studies suggests that osteocalcin plays an important role not only in bone metabolism, but also in glucose and lipid metabolism and the development of obesity.1–3 Studies involving animal models have shown that osteocalcin-deficient mice exhibit glucose intolerance, increased fat mass and increased insulin resistance. The glycolipid metabolic abnormalities and adipose accumulation in these mice can be improved by the administration of recombinant osteocalcin, which may promote insulin secretion.4,5 Obesity, especially abdominal obesity (visceral obesity), is a generally accepted cardiovascular risk factor.6–8 Computed tomography (CT) and magnetic resonance imaging (MRI) are the recommended gold standard techniques with which to accurately evaluate a patient’s visceral adipose deposition.9 However, measurement of waist circumference (W) is an easy anthropometric method with which to determine the presence of visceral obesity. Sex-related differences exist in both the levels of circulating osteocalcin and body adipose deposition, and the relationship between visceral obesity and the serum osteocalcin level in men has been fully elucidated. Several clinical studies of men,10,11 including our study,12 have shown that the serum osteocalcin level is negatively correlated with W and independently correlated with visceral fat content as measured by CT or MRI. A prospective study of an obese population including both men and premenopausal women found that an increasing serum osteocalcin level was positively correlated with a decreasing visceral fat content.13 Studies of postmenopausal women have shown that the serum osteocalcin level is negatively associated with abdominal obesity.14–17 However, these studies adopted simple methods to 429
430 Y. Luo et al. evaluate abdominal obesity, such as measurement of W and performance of bioelectrical impedance analysis. Moreover, to the best of our knowledge, no study has focused on the association between the accurately quantified amount of visceral fat and serum osteocalcin level among Chinese postmenopausal women. Therefore, we quantified the amount of visceral fat in a largescale population of Chinese postmenopausal women using MRI, the recognized standard method for such measurement.
Subjects and methods Subjects The subjects were recruited from the Shanghai Obesity Study from December 2009 to December 2011. All participants were requested to complete a standardized questionnaire that included questions on the history of present and past illnesses and medical therapies. Subjects with any infections, fractures, malignant tumours, or hepatic or renal dysfunction that may influence the serum osteocalcin level were excluded from the study. In total, 1481 postmenopausal women with complete clinical data and abdominal MRI examination findings were finally enrolled. All participants provided written informed consent. This study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital.
Methods Physical and laboratory assessments The techniques for measurement of blood pressure, body weight and body height were described in our previous study.12 The body mass index (BMI) was calculated as body weight (kg) divided by height squared (m2). W was measured midway between the lowest rib and the iliac crest with the subject in the standing position. All subjects underwent an oral glucose tolerance test. Venous blood samples were drawn after a ≥10-h overnight fast. The subjects then ingested a 75-g oral glucose load (for participants without a prior diagnosis of diabetes mellitus) or a steamed bun containing approximately 100 g of complex carbohydrates (for participants with a self-reported history of diabetes mellitus). The fasting plasma glucose level (FPG) and 2-h postload plasma glucose level (2hPG) were measured using a standard glucose oxidase method. Glycated haemoglobin (HbA1c) level was determined by high-performance liquid chromatography (Bio-Rad Inc., Hercules, CA, USA). All lipid profiles included serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), assayed with a 7600-120 Hitachi automatic analyzer (Hitachi, Tokyo, Japan).12 TC and TG were measured by enzyme assay (Roche Diagnostics GmbH, Mannheim, Germany). HDL-C and LDL-C concentrations were measured via the direct assay method (Sekisui Medical Co. Ltd., Tokyo, Japan).16 An electrochemiluminescence immunoassay (Roche Diagnostics
GmbH) was used to measure fasting serum insulin (FINS) on a Cobas e 411 analyzer, with intra- and interassay coefficients of variation of 17% and 25%, respectively. The homoeostasis model assessment-insulin resistance index (HOMA-IR) was calculated using the following formula: HOMA-IR = FPG (mmol/ l) 9 FINS (mU/l)/225. Serum C-reactive protein (CRP) level was measured via particle-enhanced immunonephelometry using CardioPhase high-sensitivity CRP reagent (Siemens Healthcare Diagnostic Inc., Newark, NJ, USA).16 The total serum osteocalcin level was determined by an electrochemiluminescence immunoassay (Roche Diagnostics GmbH), with intra-assay and interassay coefficients of variation of 12% to 40% and 17% to 65%, respectively. Magnetic resonance imaging MRI images of the abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were obtained at the abdominal level between the fourth and fifth lumbar vertebrae in the supine position using a 30 T scanner (Achieva; Philips Medical Systems, Best, the Netherlands). A single radiological technician who was blinded to the participants’ clinical characteristics performed all measurements. The correlation coefficient for intraobserver variability was 0986 (P < 0001). The VFA and SFA images were separated by two trained observers unaware of the results using image analysis software (SLICEOMATIC, version 4.2; TomoVision Inc., Montreal, QC, Canada). A third observer who did not know the results reanalysed the image, if results of the same one differed by more than 10%.18 According to our previous study, subjects with a VFA of ≥80 cm2 were classified as abdominal obesity, and subjects with a VFA of
doi: 10.1111/cen.12793
ORIGINAL ARTICLE
Association between serum osteocalcin level and visceral obesity in Chinese postmenopausal women Yuqi Luo*,1, Xiaojing Ma*,1, Yaping Hao*, Yiting Xu*, Qin Xiong*, Junling Tang*, Xiaoping Pan*, Yunfeng Xiao†, Yuqian Bao* and Weiping Jia* *Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus and †Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
Summary Background A low serum osteocalcin level, visceral obesity and postmenopausal status are recognized risk factors for cardiovascular disease. Objective We investigated the relationship between the serum osteocalcin level and visceral fat content in a population of Chinese postmenopausal women. Design and patients In total, 1481 postmenopausal women (mean age standard deviation, 571 48 years) were selected from the Shanghai Obesity Study. Measurements Abdominal fat accumulation was quantified using magnetic resonance imaging. Subjects with a visceral fat area (VFA) of ≥80 cm2 were classified as abdominally obese. The total serum osteocalcin level was measured by electrochemiluminescence immunoassay. Results The median serum osteocalcin level was 2066 lg/l (interquartile range, 1688–2542 lg/l). The overall prevalence of abdominal obesity was 491% (n = 727). Abdominally obese subjects had lower serum osteocalcin levels than did nonabdominally obese subjects [1914 (1602–2382) vs 2197 (1814– 2677) lg/l, respectively; P < 0001]. Partial correlation analysis showed that the serum osteocalcin level was still negatively correlated with VFA after adjusting for age, years since menopause and body mass index (P < 001). Moreover, VFA was independently associated with the serum osteocalcin level after adjustment for confounding factors (P < 005). A low serum osteocalcin level was an independent risk factor for abdominal obesity (odds ratio, 0972; 95% confidence interval, 0953– 0991; P = 0004).
Correspondence: Prof. Yuqian Bao, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Tel.: 86 21 64369181; Fax: 86 21 64368031; E-mail: [email protected] 1
These two authors contributed equally to this work.
© 2015 John Wiley & Sons Ltd
Conclusion The serum osteocalcin level was inversely correlated with the visceral fat content in these Chinese postmenopausal women. (Received 18 December 2014; returned for revision 3 January 2015; finally revised 16 March 2015; accepted 9 April 2015)
Introduction Osteocalcin, an osteoblast-specific protein, is a marker of osteogenesis and bone turnover. Evidence from human studies suggests that osteocalcin plays an important role not only in bone metabolism, but also in glucose and lipid metabolism and the development of obesity.1–3 Studies involving animal models have shown that osteocalcin-deficient mice exhibit glucose intolerance, increased fat mass and increased insulin resistance. The glycolipid metabolic abnormalities and adipose accumulation in these mice can be improved by the administration of recombinant osteocalcin, which may promote insulin secretion.4,5 Obesity, especially abdominal obesity (visceral obesity), is a generally accepted cardiovascular risk factor.6–8 Computed tomography (CT) and magnetic resonance imaging (MRI) are the recommended gold standard techniques with which to accurately evaluate a patient’s visceral adipose deposition.9 However, measurement of waist circumference (W) is an easy anthropometric method with which to determine the presence of visceral obesity. Sex-related differences exist in both the levels of circulating osteocalcin and body adipose deposition, and the relationship between visceral obesity and the serum osteocalcin level in men has been fully elucidated. Several clinical studies of men,10,11 including our study,12 have shown that the serum osteocalcin level is negatively correlated with W and independently correlated with visceral fat content as measured by CT or MRI. A prospective study of an obese population including both men and premenopausal women found that an increasing serum osteocalcin level was positively correlated with a decreasing visceral fat content.13 Studies of postmenopausal women have shown that the serum osteocalcin level is negatively associated with abdominal obesity.14–17 However, these studies adopted simple methods to 429
430 Y. Luo et al. evaluate abdominal obesity, such as measurement of W and performance of bioelectrical impedance analysis. Moreover, to the best of our knowledge, no study has focused on the association between the accurately quantified amount of visceral fat and serum osteocalcin level among Chinese postmenopausal women. Therefore, we quantified the amount of visceral fat in a largescale population of Chinese postmenopausal women using MRI, the recognized standard method for such measurement.
Subjects and methods Subjects The subjects were recruited from the Shanghai Obesity Study from December 2009 to December 2011. All participants were requested to complete a standardized questionnaire that included questions on the history of present and past illnesses and medical therapies. Subjects with any infections, fractures, malignant tumours, or hepatic or renal dysfunction that may influence the serum osteocalcin level were excluded from the study. In total, 1481 postmenopausal women with complete clinical data and abdominal MRI examination findings were finally enrolled. All participants provided written informed consent. This study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital.
Methods Physical and laboratory assessments The techniques for measurement of blood pressure, body weight and body height were described in our previous study.12 The body mass index (BMI) was calculated as body weight (kg) divided by height squared (m2). W was measured midway between the lowest rib and the iliac crest with the subject in the standing position. All subjects underwent an oral glucose tolerance test. Venous blood samples were drawn after a ≥10-h overnight fast. The subjects then ingested a 75-g oral glucose load (for participants without a prior diagnosis of diabetes mellitus) or a steamed bun containing approximately 100 g of complex carbohydrates (for participants with a self-reported history of diabetes mellitus). The fasting plasma glucose level (FPG) and 2-h postload plasma glucose level (2hPG) were measured using a standard glucose oxidase method. Glycated haemoglobin (HbA1c) level was determined by high-performance liquid chromatography (Bio-Rad Inc., Hercules, CA, USA). All lipid profiles included serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), assayed with a 7600-120 Hitachi automatic analyzer (Hitachi, Tokyo, Japan).12 TC and TG were measured by enzyme assay (Roche Diagnostics GmbH, Mannheim, Germany). HDL-C and LDL-C concentrations were measured via the direct assay method (Sekisui Medical Co. Ltd., Tokyo, Japan).16 An electrochemiluminescence immunoassay (Roche Diagnostics
GmbH) was used to measure fasting serum insulin (FINS) on a Cobas e 411 analyzer, with intra- and interassay coefficients of variation of 17% and 25%, respectively. The homoeostasis model assessment-insulin resistance index (HOMA-IR) was calculated using the following formula: HOMA-IR = FPG (mmol/ l) 9 FINS (mU/l)/225. Serum C-reactive protein (CRP) level was measured via particle-enhanced immunonephelometry using CardioPhase high-sensitivity CRP reagent (Siemens Healthcare Diagnostic Inc., Newark, NJ, USA).16 The total serum osteocalcin level was determined by an electrochemiluminescence immunoassay (Roche Diagnostics GmbH), with intra-assay and interassay coefficients of variation of 12% to 40% and 17% to 65%, respectively. Magnetic resonance imaging MRI images of the abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were obtained at the abdominal level between the fourth and fifth lumbar vertebrae in the supine position using a 30 T scanner (Achieva; Philips Medical Systems, Best, the Netherlands). A single radiological technician who was blinded to the participants’ clinical characteristics performed all measurements. The correlation coefficient for intraobserver variability was 0986 (P < 0001). The VFA and SFA images were separated by two trained observers unaware of the results using image analysis software (SLICEOMATIC, version 4.2; TomoVision Inc., Montreal, QC, Canada). A third observer who did not know the results reanalysed the image, if results of the same one differed by more than 10%.18 According to our previous study, subjects with a VFA of ≥80 cm2 were classified as abdominal obesity, and subjects with a VFA of
