Background: The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as
well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM)
coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could
offer valuable insights into the pathophysiology of NAFLD in T2DM. Aim: To identify potential
metabolite biomarkers capable of distinguishing between NAFLD and T2DM. Methods: A
training model was developed involving 399 participants, comprising 113 healthy controls (HCs),
134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD.
External validation encompassed 172 participants. NAFLD patients were divided based on liver
fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least
squares-discriminant analysis, logistic regression, receiver operating characteristic curve
analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum
biomarkers.
Results: Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of
specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM,
while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and
γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort
substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM
patients. Conclusion: This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as
biomarkers in the pathogenesis of NAFLD.
World J Diabetes, 2024, 2024 May 15;15(5):898-913. doi: 10.4239/wjd.v15.i5.898