Adiposity and inflammation mediate altered metabolic profile in individuals with opioid use disorder

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 body mass index (BMI), 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_1,481 = 12.9, p < 0.001), higher HbA1c (F_1,481 = 10.5, p = 0.001), lower high-density lipoprotein cholesterol (HDL-C; F_1,481 = 46.2, p < 0.001), higher low-density lipoprotein cholesterol (LDL-C; F_{1, 481} = 11.9, p < 0.001), and higher AIP (F_1,481 = 20.7, p < 0.001) compared to non-OUD. Inflammatory markers were also elevated in individuals with OUD, including CRP (F_1,481 = 9.4, p = 0.002) and ESR (F_1,481 = 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.