{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:05:35Z","timestamp":1784005535416,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is one of the major risk factors for diabetes mellitus (DM), and testosterone plays a pivotal role in metabolic regulation. However, it remains unclear whether testosterone exerts a mediating effect in the association between body fat percentage (BFP) and DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data (N\u00a0=\u00a04433) from Shengjing Hospital were used to assess the BFP-DM association, modeled via restricted cubic spline (RCS). Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, N\u00a0=\u00a04772) were then used for observational validation of the mediating pathway and analysis of gender differences. Cross-sectional NHANES data validated the mediating pathway and examined gender differences. Causal relationships of BFP with a mediator (testosterone) and outcomes (blood glucose, T1DM, T2DM) were evaluated using Mendelian randomization (MR), with inverse variance weighting (IVW) as the primary analysis. Sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) assessed pleiotropy and heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical data showed BFP was associated with DM (OR\u00a0=\u00a02.684, 95% CI 1.981-3.638). NHANES results indicated testosterone may mediate the BFP-DM association, accounting for 6.24% (95% CI 2.84%-10.68%) of the total effect, with significant gender differences: significant in males (14.92%, 95% CI 6.49%-25.29%) but not in females. MR analysis validated these associations: higher BFP may elevate blood glucose (OR\u00a0=\u00a01.147, 95% CI 1.097-1.200) and T2DM risk (OR\u00a0=\u00a02.456, 95% CI 2.120-2.845), while reducing testosterone (OR\u00a0=\u00a00.614, 95% CI 0.521-0.724). Mediation analysis showed testosterone partially mediated BFP\u2019s effect on blood glucose (8.63%, 95% CI 2.19%-15.10%) and T2DM risk (3.80%, 95% CI 0.62%-6.98%), but no significant mediation was found for BFP and T1DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study speculates that testosterone partially mediates the effect of BFP on DM risk, especially in males. However, further prospective studies are needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1872434","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:22:36Z","timestamp":1784002956000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The mediating role of testosterone in the relationship between body fat percentage and diabetes mellitus risk"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongdong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Fourth Affiliated Hospital of Nanjing Medical University (Nanjing Pukou Hospital)","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shengjing Hospital of China Medical 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