{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:16:18Z","timestamp":1783664178942,"version":"3.55.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"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>Background<\/jats:title>\n                    <jats:p>Sleep fragmentation impairs health and quality of life, yet its relationship with glucose\u2013lipid metabolic dysregulation remains unclear. This study investigated this association in obstructive sleep apnea (OSA), with a focus on nocturnal hypoxia and hypoxia-related brainstem cellular responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This large-scale cross-sectional study included 5,885 adults with suspected OSA from the Shanghai Sleep Health Study. Glucose\u2013lipid metabolic status was assessed using the triglyceride\u2013glucose (TyG) index, TyG-body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), and metabolic syndrome. Sleep fragmentation was quantified by the micro-arousal index (MAI). Multivariable regression, restricted cubic spline, threshold effect, multiplicative and additive interaction, stratified analyses, Benjamini\u2013Hochberg false discovery rate (FDR) correction were performed. GEO single-nucleus analyses were conducted to explore intermittent hypoxia-related cellular and metabolic pathway responses in the brainstem (metabolic activity scoring, GSVA, scTenifoldKnk).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TyG, TyG-BMI, and METS-IR were independently positively associated with MAI. Each 1-unit increase in TyG was associated with a 4.0-unit increase in MAI (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f4.0,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). TyG-BMI and METS-IR showed significant nonlinear dose\u2013response relationships with thresholds at 310.31 and 57.25, respectively. OSA severity and nocturnal hypoxia significantly strengthened these associations through both multiplicative and additive interactions. When AHI\u202f&amp;gt;\u202f5, the associations of TyG (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f4.04), TyG-BMI (\u03b2\u202f=\u202f0.08), and METS-IR (\u03b2\u202f=\u202f0.41) on MAI were more pronounced. Combined exposure was associated with 4.07\u20135.91-fold higher odds of elevated MAI. All primary associations remained significant after FDR correction. Single-nucleus analyses suggested widespread glucose\u2013lipid metabolic reprogramming in brainstem cells, particularly neurons and oligodendrocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glucose\u2013lipid metabolic abnormalities were significantly associated with OSA-related sleep fragmentation, and these associations were stronger among participants with greater OSA severity and nocturnal hypoxia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1859107","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:15Z","timestamp":1783661955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucose\u2013lipid metabolic dysregulation and sleep fragmentation in obstructive sleep apnea: insights from a large-scale cross-sectional study and exploratory hypoxia-related single-nucleus transcriptomic analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhicheng","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Sleep Disordered Breathing","place":["Shanghai, China"]},{"name":"Otorhinolaryngology Institute of Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head& Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Jiaotong University School of Medicine Ear Institute","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head& Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Jiaotong University School of Medicine Ear Institute","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Huai","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck, The Affiliated Huai\u2019an Hospital of Xuzhou Medical University","place":["Huaian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Sleep Disordered Breathing","place":["Shanghai, China"]},{"name":"Otorhinolaryngology Institute of Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Sleep Disordered Breathing","place":["Shanghai, China"]},{"name":"Otorhinolaryngology Institute of Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankai","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Sleep Disordered Breathing","place":["Shanghai, China"]},{"name":"Otorhinolaryngology Institute of Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S2213-2600(19)30198-5","article-title":"Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis","volume":"7","author":"Benjafield","year":"2019","journal-title":"Lancet Respir 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