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

Authors: TAS, EMIR - University Arkansas For Medical Sciences (UAMS); FLINT, AMANDA - University Of Pittsburgh Medical Center; LIBMAN, INGRID - University Of Pittsburgh Medical Center; MUZUMDAR, RADHIKA - University Of Pittsburgh Medical Center; OU, XIAWEI - University Arkansas For Medical Sciences (UAMS); WILLIAMS, DAVID - University Arkansas For Medical Sciences (UAMS); BORSHEIM, ELISABET - University Arkansas For Medical Sciences (UAMS); DIAZ, EVA - University Arkansas For Medical Sciences (UAMS)

Submitted to: Obesity Pillars
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2025
Publication Date: 3/20/2025
Citation: Tas, E., Flint, A., Libman, I., Muzumdar, R., Ou, X., Williams, D.K., Borsheim, E., Diaz, E. 2025. The association between hepatic steatosis, vitamin D status, and insulin resistance in adolescents with obesity. Obesity Pillars. 14(2025):100173. https://doi.org/10.1016/j.obpill.2025.100173.
DOI: https://doi.org/10.1016/j.obpill.2025.100173

Interpretive Summary: Problem: Low levels of vitamin D have been linked to problems with how the body uses insulin—a hormone that helps control blood sugar. This is especially concerning for teenagers, as insulin resistance can lead to health problems like type 2 diabetes. However, studies testing whether improving vitamin D levels actually helps with insulin resistance have shown mixed results. Scientists believe that other factors might play a role in how vitamin D affects insulin and overall metabolic health. Accomplishment: This study followed 44 teenagers over six months to explore how changes in vitamin D levels affect insulin resistance, a risk factor for type 2 diabetes. Researchers used advanced imaging to measure liver fat and assessed insulin resistance using two tests: HOMA-IR and the triglyceride-to-HDL cholesterol ratio (TG/HDL). They found that teens whose vitamin D levels remained low or decreased had worse insulin resistance, especially if they had higher liver fat. This relationship was most pronounced in Hispanic adolescents when measured by HOMA-IR. In contrast, the TG/HDL test showed a similar pattern across all participants, regardless of ethnicity. These findings suggest that liver fat and race or ethnicity may influence how vitamin D impacts metabolic health in adolescents. Contribution to Solving the Problem: These findings suggest that vitamin D’s role in improving insulin resistance may be influenced by both liver fat levels and racial or ethnic background, which could help explain why previous studies have produced mixed results. While this study provides important insights, larger and more controlled trials are needed to confirm these observations. Nonetheless, the results highlight the importance of considering liver health and population diversity in future research and may help inform the development of more personalized strategies to prevent or manage insulin-related problems in adolescents at risk for metabolic diseases.

Technical Abstract: 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 (ß = 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 (ß = -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 (ß = 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 (ß = 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.