{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:08:28Z","timestamp":1779170908807,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder linked to increased risk of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). The Non-HDL-to-HDL Cholesterol Ratio (NHHR) is an emerging lipid marker, but its predictive value for T2DM and CHD in NAFLD patients is unclear. This study evaluated the association between NHHR and the incidence of T2DM and CHD in a large NAFLD cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study involving 13,741 NAFLD patients from the Affiliated Hospital of Guangdong Medical University (2018\u20132025) and validated our findings in NHANES cohort (1999\u20132018) comprising 5,789 individuals. Participants were stratified into quartiles, and multivariate logistic regression with restricted cubic splines assessed associations with incident T2DM and CHD, adjusting for confounders. Subgroup, interaction, and mediation analyses elucidated potential effect modifiers and mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher NHHR was independently associated with an increased risk of T2DM in both cohorts (per unit increase: OR 1.08, 95% CI 1.06\u20131.11). A nonlinear dose\u2013response relationship was observed, with a marked rise in T2DM risk at higher NHHR levels, and participants in the highest NHHR quartile had 67% higher odds of T2DM compared with the lowest quartile. Mediation analysis indicated that fasting glucose accounted for over half of the NHHR\u2013T2DM association. In contrast, the association between NHHR and CHD was weaker and less consistent across cohorts, suggesting heterogeneity in its cardiovascular predictive value among patients with NAFLD. Findings for T2DM were robust across major subgroups and externally validated in NHANES.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NHHR is a simple, readily available lipid index that independently predicts incident T2DM in patients with NAFLD. Its nonlinear risk pattern and partial mediation through glucose metabolism underscore its clinical utility for early risk stratification and personalized prevention strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1750177","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:39:18Z","timestamp":1779169158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-HDL-to-HDL cholesterol ratio predicts incident T2DM and CHD in non-alcoholic fatty liver disease: evidence from a large clinical cohort and NHANES"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanqi","family":"Kou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanxuan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoyan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jietao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiying","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bohuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shicai","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: a multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nrneph.2017.16","article-title":"Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease","volume":"13","author":"Targher","year":"2017","journal-title":"Nat Rev 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