Relationship between serum circulating insulin-like growth factor-1 and liver fat in the United States

Background and Aim Nonalcoholic fatty liver disease (NAFLD), circulating insulin‐like growth factor‐1 (IGF‐1), and IGF‐1/IGF‐binding protein‐3 (IGFBP‐3) concentrations are associated with adiposity and insulin resistance. We aimed to determine whether serum IGF‐1, IGFBP‐3, and IGF‐1/IGFBP‐3 are associated with presence or severity of NAFLD independent of potential confounding. Methods We performed a cross‐sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988–1994, a representative sample of the United States adult population. Among participants who had a fasting blood draw and ultrasound examination, we excluded those with missing data, viral hepatitis, iron overload, excessive alcohol intake, pregnancy, or taking glucose‐lowering therapy, yielding 4172 adults for this analysis. Results In logistic regression analyses adjusted for age, gender, and race/ethnicity, higher IGF‐1 and IGF‐1/IGFBP‐3 quartiles were associated with lower likelihood of NAFLD and lower grade steatosis. These associations became non‐significant when further adjusted for adiposity (body mass index, waist circumference) with the exception of the association between IGF‐1/IGFBP‐3 and severity of NAFLD which remained significant after adjustment for homeostasis model assessment for insulin resistance (HOMA‐IR) (odds ratio [95% CI]: Q3: 0.71 [0.53–0.96], Q4: 0.62 [0.43–0.89]) and adiposity (Q4: 0.67 [0.47–0.96]). Full adjustment (age, gender, race/ethnicity, adiposity, HOMA‐IR, A1C%) further attenuated associations between IGF‐1 or IGF‐1/IGFBP‐3 and liver fat such that they were no longer significant. Conclusions Adiposity explains much of the observed association between IGF‐1 or IGF‐1/IGFBP‐3 and liver fat. These findings do not support a direct role for the growth hormone‐IGF‐1/IGFBP‐3 axis in the pathophysiology of NAFLD.