{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:03:18Z","timestamp":1787806998057,"version":"build-2784847793"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>High-density lipoprotein cholesterol (HDL-C) plays a significant role in regulating bone mineral density (BMD), with this relationship being influenced by insulin resistance. Although previous studies have investigated the relationship between HDL-C and BMD in patients with type 2 diabetes mellitus (T2DM), the impact of fasting blood glucose (FBG) on this association remains unclear. This study analyzes health screening data from T2DM patients to investigate the relationship between lumbar BMD and serum HDL-C, while also examining how FBG mediates this association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective analysis involved T2DM patients who underwent lumbar BMD screening at our hospital from January 2019 to December 2023. Lumbar BMD was measured via quantitative computed tomography. This study mainly aimed to explore the relationship between lumbar BMD and serum HDL-C in T2DM patients and assess the mediating role of FBG. Statistical analyses employed comprehensive methods: univariate analysis to examine initial variable relationships, generalized additive models for non-linear curve fitting, segmented regression for threshold effects, stratified subgroup analysis to explore potential effect modifications, and mediation analysis to explore potential indirect effect mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This work revealed that after controlling confounding factors, an independent nonlinear correlation was observed between lumbar BMD and serum HDL-C in T2DM patients. When HDL-C &amp;gt; 1.35 mmol\/L, T2DM patients\u2019 lumbar BMD shows a significant positive correlation [\u03b2=3.32, 95% confidence interval (CI): 1.43, 4.21, <jats:italic>P<\/jats:italic>=0.010)]. Subgroup analysis results indicated the consistent relationship between lumbar BMD and serum HDL-C in T2DM patients across gender (male\/female), age (\u226440 years\/&amp;gt;40, \u226460 years\/&amp;gt;60 years), and body mass index (&amp;lt;24 kg\/m<jats:sup>2<\/jats:sup>\/\u226524, &amp;lt;28 kg\/m<jats:sup>2<\/jats:sup>\/\u226528 kg\/m<jats:sup>2<\/jats:sup>) subgroups (all <jats:italic>P<\/jats:italic> interaction &amp;gt; 0.05). Analysis of the mediation effect revealed that FBG mediated 5.38% of the association, with an indirect effect of -0.142 (95% CI: -0.327, -0.026, <jats:italic>P<\/jats:italic>=0.014).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The independent nonlinear, J-shaped association between lumbar BMD and serum HDL-C in T2DM patients was detected in this study, with FBG negatively mediating this relationship. These findings prove the effect of lipid metabolism and glucose dysregulation on bone health and contribute to the development of osteoporosis prevention and treatment strategies for T2DM patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1570841","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:23:21Z","timestamp":1748841801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nonlinear relationship between lumbar bone mineral density and high-density lipoprotein cholesterol in patients with type 2 diabetes"],"prefix":"10.3389","volume":"16","author":[{"given":"Yu-Hua","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Li","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Mei","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Juan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Fang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00042","article-title":"Type 2 diabetes and osteoporosis: A guide to optimal management","volume":"102","author":"Paschou","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"Itc1","DOI":"10.7326\/AITC202401160","article-title":"Osteoporosis","volume":"177","author":"Ensrud","year":"2024","journal-title":"Ann Intern Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.afos.2020.05.006","article-title":"Systematic evidence of health economic evaluation of drugs for postmenopausal osteoporosis: A quality appraisal","volume":"6","author":"Azharuddin","year":"2020","journal-title":"Osteoporos Sarcopenia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9848-z","article-title":"Spinal deformity index in patients with type 2 diabetes","volume":"43","author":"Di Somma","year":"2013","journal-title":"Endocrine"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.v27.5","article-title":"Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures","volume":"27","author":"Kurra","year":"2011","journal-title":"Diabetes Metab Res Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1089\/biores.2016.0045","article-title":"Prevalence and risk factors of osteoporosis among Jordanian postmenopausal women attending the national center for diabetes, endocrinology and genetics in Jordan","volume":"6","author":"Hyassat","year":"2017","journal-title":"Biores Open Access"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.929709","article-title":"Inverse association between low-density lipoprotein cholesterol and bone mineral density in young- and middle-aged people: The NHANES 2011-2018","volume":"9","author":"Xiao","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-020-05762-w","article-title":"Increasing fasting glucose and fasting insulin associated with elevated bone mineral density-evidence from cross-sectional and MR studies","volume":"32","author":"Zhou","year":"2021","journal-title":"Osteoporos Int"},{"key":"B9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s11657-019-0579-0","article-title":"Association between serum high-density lipoprotein cholesterol and bone health in the general population: a large and multicenter study","volume":"14","author":"Jiang","year":"2019","journal-title":"Arch Osteoporos"},{"key":"B10","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1186\/s13018-023-04275-6","article-title":"Association between triglyceride-glucose index and bone mineral density in US adults: a cross sectional study","volume":"18","author":"Zhan","year":"2023","journal-title":"J Orthop Surg Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081869","article-title":"HDL in atherosclerotic cardiovascular disease: in search of a role","volume":"10","author":"Casula","year":"2021","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-018-06846-w","article-title":"High-density lipoprotein function and dysfunction in health and disease","volume":"33","author":"Chiesa","year":"2019","journal-title":"Cardiovasc Drugs Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13018-022-02986-w","article-title":"Positive association between high-density lipoprotein cholesterol and bone mineral density in U.S. adults: the NHANES 2011-2018","volume":"17","author":"Xie","year":"2022","journal-title":"J Orthop Surg Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12944-024-02023-1","article-title":"Association between high-density lipoprotein cholesterol and lumbar bone mineral density in Chinese: a large cross-sectional study","volume":"23","author":"Sun","year":"2024","journal-title":"Lipids Health Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1186\/s12891-021-04643-5","article-title":"Association between lipid biomarkers and osteoporosis: a cross-sectional study","volume":"22","author":"Kan","year":"2021","journal-title":"BMC Musculoskelet Disord"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/biom13040616","article-title":"Correlation between blood lipid level and osteoporosis in older adults with type 2 diabetes mellitus-A retrospective study based on inpatients in Beijing, China","volume":"13","author":"Zhao","year":"2023","journal-title":"Biomolecules"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076474","article-title":"Reduced high-density lipoprotein cholesterol is an independent determinant of altered bone quality in women with type 2 diabetes","volume":"24","author":"Dule","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1182866","article-title":"Apolipoprotein A1 is associated with osteocalcin and bone mineral density rather than high-density lipoprotein cholesterol in Chinese postmenopausal women with type 2 diabetes mellitus","volume":"10","author":"Wang","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.bone.2019.05.037","article-title":"Causal link between lipid profile and bone mineral density: A Mendelian randomization study","volume":"127","author":"Yang","year":"2019","journal-title":"Bone"},{"key":"B20","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4244\/EIJ-D-23-00124","article-title":"The 17th expert consensus document of the European Bifurcation Club - techniques to preserve access to the side branch during stepwise provisional stenting","volume":"19","author":"Pan","year":"2023","journal-title":"EuroIntervention"},{"key":"B21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12902-022-01076-6","article-title":"The study of bone mineral density measured by quantitative computed tomography in middle-aged and elderly men with abnormal glucose metabolism","volume":"22","author":"Zhang","year":"2022","journal-title":"BMC Endocr Disord"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4187","article-title":"Opportunistic screening using low-dose CT and the prevalence of osteoporosis in China: A nationwide, multicenter study","volume":"36","author":"Cheng","year":"2021","journal-title":"J Bone Miner Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.012","article-title":"Relationship between abdominal fat and bone mineral density in white and African American adults","volume":"50","author":"Katzmarzyk","year":"2012","journal-title":"Bone"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.06.001","article-title":"Extragonadal effects of follicle-stimulating hormone on osteoporosis and cardiovascular disease in women during menopausal transition","volume":"29","author":"Zhu","year":"2018","journal-title":"Trends Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12944-019-1034-3","article-title":"Prevalence of dyslipidemia associated with complications in diabetic patients: a nationwide study in Thailand","volume":"18","author":"Narindrarangkura","year":"2019","journal-title":"Lipids Health Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0023-5","article-title":"Dyslipidemia in type 2 diabetes: prevalence, pathophysiology, and management","volume":"73","author":"Chehade","year":"2013","journal-title":"Drugs"},{"key":"B27","doi-asserted-by":"publisher","first-page":"189","DOI":"10.5223\/pghn.2020.23.3.189","article-title":"Novel insights into the pathogenesis and management of the metabolic syndrome","volume":"23","author":"Wang","year":"2020","journal-title":"Pediatr Gastroenterol Hepatol Nutr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13098-022-00832-x","article-title":"The association between diabetes coexisting with low levels of high-density lipoprotein cholesterol and peritoneal dialysis-related peritonitis","volume":"14","author":"Zhang","year":"2022","journal-title":"Diabetol Metab Syndr"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.3390\/healthcare12242502","article-title":"Insulin resistance and bone mineral density: A comprehensive examination using UK biobank data","volume":"12","author":"Hung","year":"2024","journal-title":"Healthcare (Basel Switzerland)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"10760296221079334","DOI":"10.1177\/10760296221079334","article-title":"Analysis of the correlation between the ratio of monocytes to high-density lipoprotein cholesterol and in-stent restenosis in patients with premature coronary heart disease","volume":"28","author":"Chen","year":"2022","journal-title":"Clin Appl Thromb Hemost"},{"key":"B31","doi-asserted-by":"publisher","first-page":"100699","DOI":"10.1016\/j.crfs.2024.100699","article-title":"Glucosamine attenuates alcohol-induced acute liver injury via inhibiting oxidative stress and inflammation","volume":"8","author":"Lai","year":"2024","journal-title":"Curr Res Food Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2019.01.003","article-title":"Proteomics analysis of lipid droplets from the oleaginous alga chromochloris zofingiensis reveals novel proteins for lipid metabolism","volume":"17","author":"Wang","year":"2019","journal-title":"Genomics Proteomics Bioinf"},{"key":"B33","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1186\/s13018-023-04237-y","article-title":"Analysis of the predictive value of the Geriatric Nutritional Risk Index for osteoporosis in elderly patients with T2DM: a single-center retrospective study","volume":"18","author":"Sun","year":"2023","journal-title":"J Orthop Surg Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05410-w","article-title":"Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study","volume":"64","author":"Mitchell","year":"2021","journal-title":"Diabetologia"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00674","article-title":"Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men","volume":"103","author":"Lamb","year":"2018","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1570841\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:23:21Z","timestamp":1748841801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1570841\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":35,"alternative-id":["10.3389\/fendo.2025.1570841"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1570841","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"article-number":"1570841"}}