{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:06:12Z","timestamp":1776791172098,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,18]]},"group-title":"Addiction Medicine","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Previous studies have linked opioid use to altered metabolic profiles, but findings have been inconsistent and mechanisms remain unclear. One potential mechanism involves increased adiposity, leading to chronic low-grade inflammation that elevates metabolic risk. Here, we examined metabolic profiles in individuals with opioid use disorder (OUD) and matched non-OUD controls, focusing on the sequential mediating roles of BMI and inflammation. Data from individuals with OUD (n=281) and non-OUD (n=246) were drawn from a natural history screening protocol from the National Institute on Alcohol Abuse and Alcoholism intramural program. Groups were matched on age, sex, race, ethnicity, socioeconomic status, and education via propensity score matching. Metabolic measures included BMI, blood glucose, hemoglobin A1c (HbA1c), and lipid profiles, with lipid imbalance indexed by the atherogenic index of plasma (AIP). Inflammatory markers included C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Individuals with OUD had significantly higher BMI (F\n                  <jats:sub>1,481<\/jats:sub>\n                  =12.9, p&lt;0.001), HbA1c (F\n                  <jats:sub>1,481<\/jats:sub>\n                  =10.5, p=0.001), lower high-density lipoprotein cholesterol (HDL-C; F\n                  <jats:sub>1,481<\/jats:sub>\n                  = 46.2, p&lt; 0.001), higher low-density lipoprotein cholesterol (LDL-C; F\n                  <jats:sub>1,<\/jats:sub>\n                  <jats:sub>481<\/jats:sub>\n                  =11.9, p&lt; 0.001), and higher AIP (F\n                  <jats:sub>1,481<\/jats:sub>\n                  =20.7, p&lt; 0.001) compared to non-OUD. Inflammatory markers were also elevated in individuals with OUD, including CRP (F\n                  <jats:sub>1,481<\/jats:sub>\n                  =9.4, p=0.002) and ESR (F\n                  <jats:sub>1,481<\/jats:sub>\n                  =7.4, p= 0.007), and statistically mediated group differences in AIP and HbA1c, respectively. Our results are consistent with prior evidence of metabolic dysfunctions in individuals with OUD and suggest inflammation as a contributing mechanism. Targeting metabolic health and inflammation may offer new avenues for improving long-term health outcomes in OUD.\n                <\/jats:p>","DOI":"10.64898\/2026.04.13.26350800","type":"posted-content","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T21:30:17Z","timestamp":1776547817000},"source":"Crossref","is-referenced-by-count":0,"title":["Adiposity and inflammation mediate altered metabolic profiles in individuals with opioid use disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-4811","authenticated-orcid":false,"given":"Xinyi","family":"Li","sequence":"first","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-357X","authenticated-orcid":false,"given":"Peter","family":"Manza","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Maryland, Baltimore MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-9905","authenticated-orcid":false,"given":"Gene-Jack","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0368-1780","authenticated-orcid":false,"given":"Natasha","family":"Giddens","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Donald and Barbara Zucker School of Medicine, Hofstra University, Glen Oaks, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-0181","authenticated-orcid":false,"given":"Annabelle","family":"Belcher","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Maryland, Baltimore MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-4900","authenticated-orcid":false,"given":"Melanie","family":"Schwandt","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-8455","authenticated-orcid":false,"given":"Nancy","family":"Diazgranados","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-0323","authenticated-orcid":false,"given":"Kevin G.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-0908","authenticated-orcid":false,"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-2034","authenticated-orcid":false,"given":"Zhenhao","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-8794","authenticated-orcid":false,"given":"Corinde E.","family":"Wiers","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042109150954000_2026.04.13.26350800v1.1","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S0002-8223(21)01747-8","article-title":"Position of the American Dietetic Association: nutrition intervention in treatment and recovery from chemical dependency","volume":"90","year":"1990","journal-title":"Journal of the American Dietetic Association"},{"key":"2026042109150954000_2026.04.13.26350800v1.2","unstructured":"Administration, S.A.a.M.H.S., 2024. 2023 Companion infographic report: Results from the 2021, 2022, and 2023 National Surveys on Drug Use and Health. 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