Dataset Information

Association between serum osteocalcin and markers of metabolic phenotype.

ABSTRACT: Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals.Our objective was to examine the association between serum osteocalcin concentration and markers of dysmetabolic phenotype using data from a completed clinical trial in adults age 65 and older [n = 380, mean age 71 yr, body mass index (BMI) 26.9 kg/m(2), 5% with diabetes].In cross-sectional analyses (baseline data), we estimated the associations of serum osteocalcin and urine N-telopeptide with markers of metabolic phenotype including fasting plasma glucose (FPG) (primary outcome), fasting insulin, insulin sensitivity estimated by homeostasis model assessment for insulin resistance, plasma high-sensitivity C-reactive protein, IL-6, and measures of adiposity (BMI and body fat) (secondary outcomes) after multivariate adjustment for potential confounders. In prospective analysis (placebo arm), we estimated the associations of osteocalcin and N-telopeptide with change in the primary outcome, FPG, over a 3-yr period.In cross-sectional analyses, serum osteocalcin concentration was inversely associated with FPG (P = 0.01), fasting insulin (P = 0.006), homeostasis model assessment for insulin resistance (P = 0.002), high-sensitivity C-reactive protein (P = 0.01), IL-6 (P = 0.02), BMI (P < 0.001), and body fat (P < 0.001). When participants were divided into tertiles by serum osteocalcin, mean FPG was 97.1 vs. 104.8 mg/dl in the highest vs. lowest osteocalcin tertile, respectively (P < 0.01). In prospective analyses, exposure to higher osteocalcin levels during follow-up was associated with a significantly lower rise in FPG at 3 yr. Urine N-telopeptide was not associated with any marker of metabolic phenotype.Serum osteocalcin concentration was inversely associated with blood markers of dysmetabolic phenotype and measures of adiposity. Our findings should be considered hypothesis generating, and they need to be replicated in human studies designed to test the hypothesis that osteocalcin affects metabolism.

SUBMITTER: Pittas AG

PROVIDER: S-EPMC2681283 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Association between serum osteocalcin and markers of metabolic phenotype.

Pittas Anastassios G AG Harris Susan S SS Eliades Myrto M Stark Paul P Dawson-Hughes Bess B

The Journal of clinical endocrinology and metabolism 20081216 3

<h4>Context</h4>Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals.<h4>Objective</h4>Our objective was to examine the association between serum osteocalcin concentration and markers of dysmetabolic phenotype using data from a completed clinical trial in adults age 65 and older [n = 380, mean age 71 yr, body mass index (BMI) 26.9 kg/m(2), 5% with diabetes].<h4>Research design and methods</h4>In cross-sec ...[more]

PMID: 19088165

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Project description:BackgroundOsteocalcin is known to regulate energy metabolism. Recently, metabolic syndrome (MetS) has been found to be associated with reduced levels of osteocalcin in men, as well as in postmenopausal women. The aim of this study was to investigate the association between serum osteocalcin and MetS in premenopausal women, compared with that in postmenopausal women.MethodsThis cross-sectional study was based on 5,896 participants who completed a health screening examination. They were classified according to their menopausal status. Each group was subdivided into non-MetS and MetS groups according to the modified National Cholesterol Education Program-Adult Treatment Panel III criteria. Serum osteocalcin levels were measured using the electrochemiluminescence immunoassay.ResultsSerum osteocalcin level was significantly lower in women with MetS than in those without MetS, after adjusting for confounders (14.12 ± 0.04 vs. 13.17 ± 0.13 [P = 0.004] in premenopausal women, and 20.34 ± 0.09 vs. 19.62 ± 0.21 [P < 0.001] in postmenopausal women), regardless of their menopausal status. Serum osteocalcin levels decreased correspondingly with an increasing number of MetS elements (P for trend < 0.001). Multiple regression analysis demonstrated that waist circumference (β = -0.085 [P < 0.001] and β = -0.137 [P < 0.001]) and hemoglobin A1c (β = -0.09 [P < 0.001] and β = -0.145 [P < 0.001]) were independent predictors of osteocalcin in premenopausal and postmenopausal women. Triglyceride levels were also independently associated with osteocalcin levels in premenopausal women (β = -0.004 [P < 0.013]). The odds ratio (OR) for MetS was significantly higher in the lowest quartile than in the highest quartile of serum osteocalcin levels after adjusting for age, alkaline phosphatase, uric acid, high sensitivity C-reactive protein, and body mass index in all women (OR, 2.00; 95% confidence interval [CI], 1.49-2.68) as well as in premenopausal (OR, 2.23; 95% CI, 1.39-3.58) and postmenopausal (OR, 2.01; 95% CI, 1.26-3.23) subgroups.ConclusionLower serum osteocalcin concentrations were significantly associated with MetS in both premenopausal and postmenopausal women and were therefore independent of menopausal status.

Project description:INTRODUCTION:The global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and improve insulin sensitivity in mice. Observational studies in humans have investigated the relationship between OC and metabolic parameters, and T2DM. Importantly, few studies have reported on the undercarboxylated form of OC (ucOC), which is the putative active form of OC suggested to affect glucose metabolism. OBJECTIVES:We will conduct a systematic review and meta-analysis to: (1) compare the levels of serum OC and ucOC between T2DM and normal glucose-tolerant controls (NGC); (2) investigate the risk ratios between serum OC and ucOC, and T2DM; (3) determine the correlation coefficient between OC and ucOC and fasting insulin levels, homeostatic model assessment-insulin resistance, haemoglobin A1c and fasting glucose levels and (4) explore potential sources of between-study heterogeneity. The secondary objective is to compare the serum OC and ucOC between pre-diabetes (PD) and NGC and between T2DM and PD. HODS AND ANALYSIS:This study will report items in line with the guidelines outlined in preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology. We will include observational studies (cohort, case-control and cross-sectional studies) and intervention studies with baseline data. Three databases (MEDLINE, EMBASE and SCOPUS) will be searched from inception until July 2018 without language restrictions. Two reviewers will independently screen the titles and abstracts and conduct a full-text assessment to identify eligible studies. Discrepancies will be resolved by consensus with a third reviewer. The risk of bias assessment will be conducted by two reviewers independently based on the Newcastle-Ottawa Scale. Potential sources of between-study heterogeneity will be tested using meta-regression/subgroup analyses. Contour-enhanced funnel plots and Egger's test will be used to identify potential publication bias. ETHICS AND DISSEMINATION:Formal ethical approval is not required. We will disseminate the results to a peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER:CRD42017073127.

Project description:BackgroundAvailable evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.MethodsA total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms.ResultsCompared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P < 0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73 ± 8.18 ng/mL) compared with healthy controls (15.3 ± 6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls.ConclusionsThese findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.

Project description:Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (?88 cm); elevated blood pressure (?130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m2 with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m2 and ?1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR?=?1.26, 95% CI: 1.01-1.56), as did women with a BMI ?25 kg/m2 and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR?=?1.24, 95% CI: 0.99-1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ?88 cm, waist circumference ?80 cm, and waist-hip ratio ?0.85 of 1.58, 95% CI: 1.02-2.46; 1.38, 95% CI: 1.09-1.75; and 1.38, 95% CI: 1.02-1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR?=?0.71, 95% CI: 0.52-0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.

Dataset Information

Association between serum osteocalcin and markers of metabolic phenotype.

Publications

Association between serum osteocalcin and markers of metabolic phenotype.

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