The association between hepatic steatosis, vitamin D status, and insulin resistance in adolescents with obesity

Introduction: Epidemiological studies suggest an inverse relationship between circulating 25-hydroxy-vitamin D [25(OH)D] levels and insulin resistance (IR), yet interventional studies have yielded inconsistent findings. This study examined the relationship between changes in vitamin D status and markers of IR in adolescents, with a focus on the modifying effect of liver fat. Methods: A post-hoc analysis was performed using data from 44 adolescents participating in a 6-month observational study evaluating biomarkers of hepatosteatosis. Participants were categorized into two groups based on vitamin D status at the end of the observation period: those whose vitamin D levels increased or remained sufficient (VDI, n = 22) and those whose levels decreased or remained insufficient/deficient (VDD, n = 22). Liver fat percentage was measured using magnetic resonance imaging (MRI) fat-fraction, and IR was assessed using the updated Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR) and the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL). Results: Across the cohort, liver fat was positively associated with HOMA2-IR (β = 0.08, p = 0.023). The association between changes in vitamin D status and HOMA2-IR trajectories was modified by liver fat but only in Hispanic adolescents (β = −0.18, p < 0.001). Among Hispanic adolescents in the VDD group, HOMA-IR worsened, particularly at higher levels of liver fat. In non-Hispanic adolescents, HOMA-IR increased in the VDD group (β = 0.65, p = 0.033) compared to the VDI group, independent of baseline liver fat. Across the cohort, changes in vitamin D status interacted with liver fat to influence TG/HDL trajectories (β = 0.20, p = 0.034). Conclusions: The metabolic response to changes in vitamin D status in adolescents with IR may vary based on racial and ethnic differences and liver fat status. These findings underscore the importance of considering liver fat and racial/ethnic background in vitamin D and metabolic health studies. Future research with more extensive and diverse cohorts spanning the fatty liver disease spectrum is needed to clarify these relationships.