{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:07:43Z","timestamp":1787238463654,"version":"build-2736575974"},"reference-count":48,"publisher":"The Endocrine Society","issue":"11","funder":[{"name":"Intramural Research Programs of the National Institute of Diabetes"},{"name":"Digestive and Kidney Diseases"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N\u2005=\u200527), and 3 to 5 years (N\u2005=\u200523) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg\/dL at baseline, 1 year, 3-5 years, P\u2005&amp;lt;\u2005.0001), A1c (9.5\u2005\u00b1\u20053.0, 6.5\u2005\u00b1\u20051.6, 6.5\u2005\u00b1\u20051.9%, P\u2005&amp;lt;\u2005.001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P\u2005&amp;lt;\u2005.001). Only HOMA-IR improved in PLD (P\u2005&amp;lt;\u2005.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8\u2005\u00b1\u20051.7, 9.1\u2005\u00b1\u20051.3, 8.3\u2005\u00b1\u20051.7 mm, P\u2005&amp;lt;\u2005.01), and LV mass (140.7\u2005\u00b1\u200545.9, 128.7\u2005\u00b1\u200537.9, 110.9\u2005\u00b1\u200529.1 g, P\u2005&amp;lt;\u2005.01), and increased septal e\u2032 velocity (8.6\u2005\u00b1\u20051.7, 10.0\u2005\u00b1\u20052.1, 10.7\u2005\u00b1\u20052.4 cm\/s, P\u2005&amp;lt;\u2005.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e\u2032 velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metreleptin attenuated cardiac hypertrophy and improved septal e\u2032 velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab499","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T11:05:11Z","timestamp":1625483111000},"page":"e4327-e4339","source":"Crossref","is-referenced-by-count":15,"title":["Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy"],"prefix":"10.1210","volume":"106","author":[{"given":"My-Le","family":"Nguyen","sequence":"first","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Sachdev","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Burklow","sequence":"additional","affiliation":[{"name":"NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Startzell","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyoung","family":"Auh","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-7382","authenticated-orcid":false,"given":"Rebecca J","family":"Brown","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"issue":"12","key":"2021120108555145100_CIT0001","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021120108555145100_CIT0002","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1210\/jc.2014-4491","article-title":"Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin","volume":"100","author":"Diker-Cohen","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021120108555145100_CIT0003","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.cell.2015.07.007","article-title":"Leptin does not mediate hypertension associated with human obesity","volume":"162","author":"Brown","year":"2015","journal-title":"Cell."},{"issue":"4","key":"2021120108555145100_CIT0004","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ahj.2014.12.021","article-title":"Metabolic and cardiac phenotype characterization in 37 atypical Dunnigan patients with nonfarnesylated mutated prelamin A","volume":"169","author":"Andre","year":"2015","journal-title":"Am Heart J."},{"issue":"4","key":"2021120108555145100_CIT0005","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/MD.0b013e3181e9442f","article-title":"Cardiomyopathy in congenital and acquired generalized lipodystrophy: a clinical assessment","volume":"89","author":"Lupsa","year":"2010","journal-title":"Medicine (Baltimore)."},{"key":"2021120108555145100_CIT0006","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13098-019-0444-8","article-title":"Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in young patients with congenital generalized lipodystrophy","volume":"11","author":"Ponte","year":"2019","journal-title":"Diabetol Metab Syndr."},{"issue":"1","key":"2021120108555145100_CIT0007","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12872-017-0738-4","article-title":"Early commitment of cardiovascular autonomic modulation in Brazilian patients with congenital generalized lipodystrophy","volume":"18","author":"Ponte","year":"2018","journal-title":"BMC Cardiovasc Disord."},{"issue":"6","key":"2021120108555145100_CIT0008","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/europace\/eup095","article-title":"Autonomic modulation in patients with congenital generalized lipodystrophy (Berardinelli-Seip syndrome)","volume":"11","author":"Faria","year":"2009","journal-title":"Europace."},{"issue":"4","key":"2021120108555145100_CIT0009","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF00441777","article-title":"Echocardiographic assessment of cardiac function and morphology in patients with generalised lipodystrophy","volume":"144","author":"Bj\u00f8rnstad","year":"1985","journal-title":"Eur J Pediatr."},{"issue":"2","key":"2021120108555145100_CIT0010","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0022-3476(86)80389-4","article-title":"Hypertrophic cardiomyopathy in total lipodystrophy","volume":"109","author":"Rheuban","year":"1986","journal-title":"J Pediatr."},{"key":"2021120108555145100_CIT0011","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1651-2227.1996.tb14264.x","article-title":"Cardiac findings in generalized lipodystrophy","volume":"413","author":"Bj\u00f8rnstad","year":"1996","journal-title":"Acta Paediatr Suppl."},{"issue":"2","key":"2021120108555145100_CIT0012","first-page":"196","article-title":"Dilated cardiomyopathy and myocardial infarction secondary to congenital generalized lipodystrophy","volume":"35","author":"Khalife","year":"2008","journal-title":"Tex Heart Inst J."},{"issue":"11","key":"2021120108555145100_CIT0013","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.acvd.2020.06.006","article-title":"Myocardial glucotoxicity: mechanisms and potential therapeutic targets","volume":"113","author":"Battault","year":"2020","journal-title":"Arch Cardiovasc Dis."},{"issue":"8","key":"2021120108555145100_CIT0014","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1210\/en.2003-0242","article-title":"Cardiac lipid accumulation associated with diastolic dysfunction in obese mice","volume":"144","author":"Christoffersen","year":"2003","journal-title":"Endocrinology."},{"issue":"5","key":"2021120108555145100_CIT0015","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.yjmcc.2008.03.008","article-title":"Insulin signaling pathways and cardiac growth","volume":"44","author":"DeBosch","year":"2008","journal-title":"J Mol Cell Cardiol."},{"issue":"8","key":"2021120108555145100_CIT0016","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJMoa012437","article-title":"Leptin-replacement therapy for lipodystrophy","volume":"346","author":"Oral","year":"2002","journal-title":"N Engl J Med."},{"issue":"10","key":"2021120108555145100_CIT0017","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1172\/JCI0215001","article-title":"Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy","volume":"109","author":"Petersen","year":"2002","journal-title":"J Clin Invest."},{"issue":"2","key":"2021120108555145100_CIT0018","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1210\/jc.2006-1546","article-title":"Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy","volume":"92","author":"Ebihara","year":"2007","journal-title":"J Clin Endocrinol Metab."},{"issue":"8","key":"2021120108555145100_CIT0019","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1172\/JCI95476","article-title":"Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy","volume":"128","author":"Brown","year":"2018","journal-title":"J Clin Invest."},{"issue":"3","key":"2021120108555145100_CIT0020","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12020-018-1589-1","article-title":"Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy","volume":"60","author":"Brown","year":"2018","journal-title":"Endocrine."},{"issue":"3","key":"2021120108555145100_CIT0021","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/s12020-019-01862-8","article-title":"Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy","volume":"64","author":"Oral","year":"2019","journal-title":"Endocrine."},{"issue":"1","key":"2021120108555145100_CIT0022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"28","author":"Lang","year":"2015","journal-title":"J Am Soc Echocardiogr."},{"issue":"4","key":"2021120108555145100_CIT0023","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.echo.2017.02.009","article-title":"Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European association of cardiovascular imaging and the American society of echocardiography","volume":"30","author":"Baumgartner","year":"2017","journal-title":"J Am Soc Echocardiogr."},{"issue":"12","key":"2021120108555145100_CIT0024","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/ehjci\/jew082","article-title":"Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American society of echocardiography and the European association of cardiovascular imaging","volume":"17","author":"Nagueh","year":"2016","journal-title":"Eur Heart J Cardiovasc Imaging."},{"issue":"7","key":"2021120108555145100_CIT0025","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.echo.2010.05.010","article-title":"Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography","volume":"23","author":"Rudski","year":"2010","journal-title":"J Am Soc Echocardiogr."},{"issue":"8","key":"2021120108555145100_CIT0026","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.jcmg.2018.07.005","article-title":"Research to practice: assessment of left ventricular global longitudinal strain for surveillance of cancer chemotherapeutic-related cardiac dysfunction","volume":"11","author":"Yang","year":"2018","journal-title":"JACC Cardiovasc Imaging."},{"issue":"2","key":"2021120108555145100_CIT0027","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7326\/0003-4819-110-2-101","article-title":"Left ventricular mass and incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study","volume":"110","author":"Levy","year":"1989","journal-title":"Ann Intern Med."},{"issue":"7","key":"2021120108555145100_CIT0028","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/S0735-1097(01)01663-1","article-title":"Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study","volume":"38","author":"Verdecchia","year":"2001","journal-title":"J Am Coll Cardiol."},{"issue":"2","key":"2021120108555145100_CIT0029","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1161\/01.HYP.35.2.580","article-title":"Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension","volume":"35","author":"Schillaci","year":"2000","journal-title":"Hypertension."},{"issue":"5","key":"2021120108555145100_CIT0030","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.amjhyper.2005.10.018","article-title":"Regression of left ventricular hypertrophy and prevention of stroke in hypertensive subjects","volume":"19","author":"Verdecchia","year":"2006","journal-title":"Am J Hypertens."},{"issue":"11 Pt 1","key":"2021120108555145100_CIT0031","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0895-7061(03)01018-5","article-title":"Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a meta-analysis","volume":"16","author":"Verdecchia","year":"2003","journal-title":"Am J Hypertens."},{"issue":"19","key":"2021120108555145100_CIT0032","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1001\/jama.292.19.2350","article-title":"Prognostic significance of left ventricular mass change during treatment of hypertension","volume":"292","author":"Devereux","year":"2004","journal-title":"JAMA."},{"issue":"19","key":"2021120108555145100_CIT0033","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1001\/jama.292.19.2343","article-title":"Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events","volume":"292","author":"Okin","year":"2004","journal-title":"JAMA."},{"key":"2021120108555145100_CIT0034","article-title":"LMNA-related dilated cardiomyopathy","volume-title":"GeneReviews\u00ae.","author":"Hershberger"},{"issue":"4","key":"2021120108555145100_CIT0035","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.2337\/db16-0733","article-title":"The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model","volume":"66","author":"Joubert","year":"2017","journal-title":"Diabetes."},{"issue":"21","key":"2021120108555145100_CIT0036","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N Engl J Med."},{"issue":"7","key":"2021120108555145100_CIT0037","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.amjcard.2013.05.036","article-title":"Cardiac steatosis and left ventricular hypertrophy in patients with generalized lipodystrophy as determined by magnetic resonance spectroscopy and imaging","volume":"112","author":"Nelson","year":"2013","journal-title":"Am J Cardiol."},{"issue":"6","key":"2021120108555145100_CIT0038","doi-asserted-by":"crossref","first-page":"500","DOI":"10.2337\/diacare.11.6.500","article-title":"Selective insulin action on skin, ovary, and heart in insulin-resistant states","volume":"11","author":"Geffner","year":"1988","journal-title":"Diabetes Care."},{"issue":"1","key":"2021120108555145100_CIT0039","first-page":"50","article-title":"Cardiomyopathy in lipodystrophy and the specificity spillover hypothesis","volume":"29","author":"Klar","year":"1993","journal-title":"Isr J Med Sci."},{"issue":"1","key":"2021120108555145100_CIT0040","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0022-3476(87)80317-7","article-title":"Hypertrophic cardiomyopathy in total lipodystrophy: insulin action in the face of insulin resistance?","volume":"110","author":"Geffner","year":"1987","journal-title":"J Pediatr."},{"issue":"9","key":"2021120108555145100_CIT0041","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/j.jacc.2004.07.050","article-title":"Plasma leptin and prognosis in patients with established coronary atherosclerosis","volume":"44","author":"Wolk","year":"2004","journal-title":"J Am Coll Cardiol."},{"issue":"3","key":"2021120108555145100_CIT0042","doi-asserted-by":"crossref","first-page":"E316","DOI":"10.1152\/ajpendo.00005.2014","article-title":"Rescue of cardiac leptin receptors in db\/db mice prevents myocardial triglyceride accumulation","volume":"307","author":"Hall","year":"2014","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"8","key":"2021120108555145100_CIT0043","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41440-018-0062-0","article-title":"Higher plasma leptin levels are associated with reduced left ventricular mass and left ventricular diastolic stiffness in black women: insights from the Genetic Epidemiology Network Of Arteriopathy (GENOA) study","volume":"41","author":"Kamimura","year":"2018","journal-title":"Hypertens Res."},{"issue":"10","key":"2021120108555145100_CIT0044","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1517\/14728222.2015.1019468","article-title":"Association between plasma leptin and adiponectin levels and diastolic function in the general population","volume":"19","author":"Fontes-Carvalho","year":"2015","journal-title":"Expert Opin Ther Targets."},{"key":"2021120108555145100_CIT0045","doi-asserted-by":"crossref","first-page":"54","DOI":"10.22146\/aci.44552","article-title":"Correlation between leptin with diastolic function in young adult obesity","volume":"5","author":"Nugraha","year":"2019","journal-title":"Acta Cardiol Indones."},{"issue":"1","key":"2021120108555145100_CIT0046","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12020-014-0450-4","article-title":"Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience","volume":"49","author":"Araujo-Vilar","year":"2015","journal-title":"Endocrine."},{"issue":"3","key":"2021120108555145100_CIT0047","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1210\/jc.2011-2229","article-title":"Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety","volume":"97","author":"Simha","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021120108555145100_CIT0048","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/HYPERTENSIONAHA.109.136655","article-title":"Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of randomized comparative studies","volume":"54","author":"Fagard","year":"2009","journal-title":"Hypertension."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgab499\/39463126\/dgab499.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/11\/e4327\/41378610\/dgab499.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/11\/e4327\/41378610\/dgab499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T08:53:22Z","timestamp":1638348802000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/11\/e4327\/6314685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,7,5]]},"published-print":{"date-parts":[[2021,10,21]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgab499","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,7,5]]}}}