{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T13:53:04Z","timestamp":1752673984662,"version":"3.37.3"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Project of National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31571212"],"award-info":[{"award-number":["31571212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Public Health"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>First-degree relatives of patients with diabetes (FDR) tend to have impaired insulin activity, which lead to the alternation of circulating cytokine levels. Liver is a main target tissue of insulin action; therefore, liver fat content (LFC) has a close relationship with insulin resistance. This study aimed to find the alteration in serum osteocalcin levels in FDR and the relationship of serum osteocalcin levels with FDR and non-alcoholic fatty liver disease (NAFLD).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In total, 1206 subjects including 413 men and 793 women from the communities, aged 59.7 (range, 54.8\u201364.3) years, were enrolled. An electrochemiluminescence immunoassay was performed to measure the levels of serum osteocalcin. LFC was measured using quantitative ultrasonography.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A significant decrease was found in serum osteocalcin levels in subjects with NAFLD (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) as well as in FDR (19.8\u2009\u00b1\u20095.7\u2009ng\/mL versus 20.7\u2009\u00b1\u20096.8\u2009ng\/mL, <jats:italic>P<\/jats:italic>\u2009=\u20090.028). Furthermore, among the subjects with NAFLD, those with FDR had lower levels of osteocalcin than those without FDR (<jats:italic>P<\/jats:italic>\u2009=\u20090.011). The presence of FDR remained a predictor for decreased serum osteocalcin levels after adjusting for body mass index, blood glucose, blood lipids, and LFC (standardized <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u2212\u20090.057, <jats:italic>P<\/jats:italic>\u2009=\u20090.028).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>FDR had lower serum osteocalcin levels than non-FDR. The inverse association between FDR and serum osteocalcin levels was independent of metabolic factors.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12889-019-7932-5","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T10:03:27Z","timestamp":1575367407000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["First-degree family history of diabetes and its relationship with serum osteocalcin levels independent of liver fat content in a non-diabetic Chinese cohort"],"prefix":"10.1186","volume":"19","author":[{"given":"Yiting","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengchen","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqian","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"key":"7932_CR1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S1521-690X(03)00041-1","volume":"17","author":"H Beck-Nielsen","year":"2003","unstructured":"Beck-Nielsen H, Vaag A, Poulsen P, Gaster M. Metabolic and genetic influence on glucose metabolism in type 2 diabetic subjects--experiences from relatives and twin studies. Best Pract Res Clin Endocrinol Metab. 2003;17:445\u201367.","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"7932_CR2","doi-asserted-by":"publisher","first-page":"e112","DOI":"10.1038\/nutd.2014.9","volume":"4","author":"CH Tam","year":"2014","unstructured":"Tam CH, Wang Y, Luan J, Lee HM, Luk AO, Tutino GE, et al. Maternal history of diabetes is associated with increased cardiometabolic risk in Chinese. Nutr Diabetes. 2014;4:e112.","journal-title":"Nutr Diabetes"},{"key":"7932_CR3","doi-asserted-by":"publisher","first-page":"e70435","DOI":"10.1371\/journal.pone.0070435","volume":"8","author":"AB Jenkins","year":"2013","unstructured":"Jenkins AB, Batterham M, Samocha-Bonet D, Tonks K, Greenfield JR, Campbell LV. Segregation of a latent high adiposity phenotype in families with a history of type 2 diabetes mellitus implicates rare obesity-susceptibility genetic variants with large effects in diabetes-related obesity. PLoS One. 2013;8:e70435.","journal-title":"PLoS One"},{"key":"7932_CR4","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.2337\/diabetes.52.7.1872","volume":"52","author":"A Kubaszek","year":"2003","unstructured":"Kubaszek A, Pihlajam\u00e4ki J, Komarovski V, Lindi V, Lindstr\u00f6m J, Eriksson J, et al. Finnish Diabetes Prevention Study. Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes. 2003;52:1872\u20136.","journal-title":"Diabetes"},{"key":"7932_CR5","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1038\/ijo.2016.147","volume":"40","author":"X Hu","year":"2016","unstructured":"Hu X, Pan X, Ma X, Luo Y, Xu Y, Xiong Q, et al. Contribution of a first-degree family history of diabetes to increased serum adipocyte fatty acid binding protein levels independent of body fat content and distribution. Int J Obes. 2016;40:1649\u201354.","journal-title":"Int J Obes"},{"issue":"5","key":"7932_CR6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1530\/EJE-09-0585","volume":"161","author":"M Zhou","year":"2009","unstructured":"Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol. 2009;161(5):723\u20139.","journal-title":"Eur J Endocrinol"},{"issue":"12","key":"7932_CR7","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1038\/aps.2017.23","volume":"38","author":"J Wang","year":"2017","unstructured":"Wang J, Yan DD, Hou XH, Bao YQ, Hu C, Zhang ZL, et al. Association of bone turnover markers with glucose metabolism in Chinese population. Acta Pharmacol Sin. 2017;38(12):1611\u20137.","journal-title":"Acta Pharmacol Sin"},{"key":"7932_CR8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1475-2840-13-74","volume":"13","author":"J Dou","year":"2014","unstructured":"Dou J, Li H, Ma X, Zhang M, Fang Q, Nie M, et al. Osteocalcin attenuates high fat diet-induced impairment of endothelium-dependent relaxation through Akt\/eNOS-dependent pathway. Cardiovasc Diabetol. 2014;13:74.","journal-title":"Cardiovasc Diabetol"},{"issue":"3","key":"7932_CR9","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","volume":"130","author":"NK Lee","year":"2007","unstructured":"Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456\u201369.","journal-title":"Cell."},{"issue":"4","key":"7932_CR10","doi-asserted-by":"publisher","first-page":"E1079","DOI":"10.1152\/ajpendo.00245.2006","volume":"292","author":"JW Bullen Jr","year":"2007","unstructured":"Bullen JW Jr, Bluher S, Kelesidis T, Mantzoros CS. Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice. Am J Physiol Endocrinol Metab. 2007;292(4):E1079\u201386.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"7932_CR11","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1111\/1440-1681.12063","volume":"40","author":"J Dou","year":"2013","unstructured":"Dou J, Ma X, Fang Q, Hao Y, Yang R, Wang F, et al. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in Chinese men. Clin Exp Pharmacol Physiol. 2013;40:282\u20138.","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"7932_CR12","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1038\/aps.2015.81","volume":"36","author":"YQ Luo","year":"2015","unstructured":"Luo YQ, Ma XJ, Hao YP, Pan XP, Xu YT, Xiong Q, et al. Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels. Acta Pharmacol Sin. 2015;36:1497\u2013502.","journal-title":"Acta Pharmacol Sin"},{"key":"7932_CR13","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/oby.2011.302","volume":"20","author":"MF Xia","year":"2012","unstructured":"Xia MF, Yan HM, He WY, Li XM, Li CL, Yao XZ, et al. Standardized ultrasound hepatic\/renal ratio and hepatic attenuation rate to quantify liver fat content: an improvement method. Obesity (Silver Spring). 2012;20:444\u201352.","journal-title":"Obesity (Silver Spring)"},{"key":"7932_CR14","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1002\/oby.21182","volume":"23","author":"MF Xia","year":"2015","unstructured":"Xia MF, Bian H, Yan HM, Lin HD, Chang XX, Li XM, et al. Assessment of liver fat content using quantitative ultrasonography to evaluate risks for metabolic diseases. Obesity (Silver Spring). 2015;23:1929\u201337.","journal-title":"Obesity (Silver Spring)"},{"key":"7932_CR15","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12933-018-0786-9","volume":"17","author":"Y Xu","year":"2018","unstructured":"Xu Y, Ma X, Pan X, He X, Xiao Y, Bao Y. Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women. Cardiovasc Diabetol. 2018;17:143.","journal-title":"Cardiovasc Diabetol"},{"key":"7932_CR16","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/joim.12289","volume":"277","author":"H Cederberg","year":"2015","unstructured":"Cederberg H, Stan\u010d\u00e1kov\u00e1 A, Kuusisto J, Laakso M, Smith U. Family history of type 2 diabetes increases the risk of both obesity and its complications: is type 2 diabetes a disease of inappropriate lipid storage? J Intern Med. 2015;277:540\u201351.","journal-title":"J Intern Med"},{"key":"7932_CR17","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1210\/jc.2012-2906","volume":"98","author":"Y Bao","year":"2013","unstructured":"Bao Y, Ma X, Yang R, Wang F, Hao Y, Dou J, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab. 2013;98:345\u201351.","journal-title":"J Clin Endocrinol Metab"},{"key":"7932_CR18","volume-title":"Report of a WHO consultation: definition, diagnosis and classification of diabetes mellitus and its complication. Part 1: Diagnosis and classification of diabetes mellitus","author":"Department of Noncommunicable Disease Surveillance","year":"1999","unstructured":"Department of Noncommunicable Disease Surveillance. Report of a WHO consultation: definition, diagnosis and classification of diabetes mellitus and its complication. Part 1: Diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999."},{"key":"7932_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/1440-1681.12853","volume":"45","author":"X Zhang","year":"2018","unstructured":"Zhang X, Shen Y, Xu Y, Xiong Q, Lu Z, Ma X, et al. Association of serum osteocalcin levels with major adverse cardiovascular events: a 4.4-year retrospective cohort study. Clin Exp Pharmacol Physiol. 2018;45:3\u20139.","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"7932_CR20","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1111\/cen.12793","volume":"83","author":"Y Luo","year":"2015","unstructured":"Luo Y, Ma X, Hao Y, Xu Y, Xiong Q, Tang J, et al. Association between serum osteocalcin level and visceral obesity in Chinese postmenopausal women. Clin Endocrinol. 2015;83:429\u201334.","journal-title":"Clin Endocrinol"},{"key":"7932_CR21","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s12020-016-0926-5","volume":"53","author":"J Du","year":"2016","unstructured":"Du J, Zhang M, Lu J, Zhang X, Xiong Q, Xu Y, et al. Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK. Endocrine. 2016;53:701\u20139.","journal-title":"Endocrine."},{"key":"7932_CR22","doi-asserted-by":"publisher","first-page":"19782","DOI":"10.3390\/ijms141019782","volume":"14","author":"JJ Liu","year":"2013","unstructured":"Liu JJ, Chen YY, Mo ZN, Tian GX, Tan AH, Gao Y, et al. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in adult males, South China. Int J Mol Sci. 2013;14:19782\u201391.","journal-title":"Int J Mol Sci"},{"key":"7932_CR23","doi-asserted-by":"publisher","first-page":"788","DOI":"10.2337\/diabetes.47.5.788","volume":"47","author":"M Ishikawa","year":"1998","unstructured":"Ishikawa M, Pruneda ML, Adams-Huet B, Raskin P. Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of individuals with type 2 diabetes. Diabetes. 1998;47:788\u201392.","journal-title":"Diabetes."},{"key":"7932_CR24","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1046\/j.1464-5491.2001.00496.x","volume":"18","author":"A Vaag","year":"2001","unstructured":"Vaag A, Lehtovirta M, Thye-R\u00f6nn P, Groop L, European Group of Insulin Resistance. Metabolic impact of a family history of type 2 diabetes. Results from a European multicentre study (EGIR). Diabet Med. 2001;18:533\u201340.","journal-title":"Diabet Med"},{"key":"7932_CR25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2337\/diacare.28.1.115","volume":"28","author":"SA Arslanian","year":"2005","unstructured":"Arslanian SA, Bacha F, Saad R, Gungor N. Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth. Diabetes Care. 2005;28:115\u20139.","journal-title":"Diabetes Care"},{"key":"7932_CR26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13098-017-0210-8","volume":"9","author":"JH Moon","year":"2017","unstructured":"Moon JH, Roh E, Oh TJ, Kim KM, Moon JH, Lim S, et al. Increased risk of metabolic disorders in healthy young adults with family history of diabetes: from the Korea National Health and nutrition survey. Diabetol Metab Syndr. 2017;9:16.","journal-title":"Diabetol Metab Syndr"},{"key":"7932_CR27","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1007\/s00125-009-1520-7","volume":"52","author":"M Stadler","year":"2009","unstructured":"Stadler M, Pacini G, Petrie J, Luger A, Anderwald C, RISC Investigators. Beta cell (dys)function in non-diabetic offspring of diabetic patients. Diabetologia. 2009;52:2435\u201344.","journal-title":"Diabetologia."},{"key":"7932_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/JCI72323","volume":"124","author":"J Wei","year":"2014","unstructured":"Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, et al. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest. 2014;124:1\u201313.","journal-title":"J Clin Invest"},{"key":"7932_CR29","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.cell.2010.06.002","volume":"142","author":"K Fulzele","year":"2010","unstructured":"Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142:309\u201319.","journal-title":"Cell."},{"key":"7932_CR30","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1007\/s12020-017-1396-0","volume":"59","author":"FL Bilotta","year":"2018","unstructured":"Bilotta FL, Arcidiacono B, Messineo S, Greco M, Chiefari E, Britti D, et al. Insulin and osteocalcin: further evidence for a mutual cross-talk. Endocrine. 2018;59:622\u201332.","journal-title":"Endocrine."}],"container-title":["BMC Public Health"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-019-7932-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12889-019-7932-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-019-7932-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T19:16:49Z","timestamp":1606850209000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpublichealth.biomedcentral.com\/articles\/10.1186\/s12889-019-7932-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["7932"],"URL":"https:\/\/doi.org\/10.1186\/s12889-019-7932-5","relation":{},"ISSN":["1471-2458"],"issn-type":[{"type":"electronic","value":"1471-2458"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"12 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted according to the World Medical Association Declaration of Helsinki and approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital. All subjects provided written informed consent before the interview.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1628"}}