Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

Susu Feng, Sijing Wang, Lin Guo, Pan-Pan Ma, Xiao-Long Ye, Ming-Lin Pan, Bo Hang, Jian-Hua Mao, A. Snijders, Yi-Bing Lu, Da-Fa Ding
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Abstract

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 pathophy-siology 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.
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2 型糖尿病患者非酒精性脂肪肝的血清胆汁酸和不饱和脂肪酸概况
背景 2 型糖尿病(T2DM)并发非酒精性脂肪肝(NAFLD)患者的胆汁酸(BA)和不饱和脂肪酸(UFA)概况及其失调情况仍难以了解。研究这些代谢物可为了解 T2DM 中非酒精性脂肪肝的病理生理学提供有价值的信息。目的 找出能够区分非酒精性脂肪肝和 T2DM 的潜在代谢物生物标志物。方法 建立了一个由 399 名参与者组成的训练模型,其中包括 113 名健康对照组 (HC)、134 名患有 T2DM 但无非酒精性脂肪肝的患者以及 152 名患有 T2DM 和非酒精性脂肪肝的患者。外部验证包括 172 名参与者。非酒精性脂肪肝患者根据肝纤维化评分进行划分。分析方法包括单变量检验、正交偏最小二乘判别分析、逻辑回归、接收器操作特征曲线分析和决策曲线分析,以确定和评估血清生物标志物的诊断价值。结果 与 HCs 相比,T2DM 和 NAFLD 组的特定 BAs 水平都有所降低。在 UFAs 中,特定酸与 T2DM 非酒精性脂肪肝风险呈正相关,而 ω-6:ω-3 UFA 比率呈负相关。在非酒精性脂肪肝中,α-亚麻酸和γ-亚麻酸的水平与明显的肝纤维化有关。验证队列证实了这些生物标志物对评估 T2DM 患者非酒精性脂肪肝风险的预测功效。结论 本研究强调了 BA 和 UFA 特征的改变与 T2DM 患者出现非酒精性脂肪肝之间的联系,提出了它们在非酒精性脂肪肝发病机制中作为生物标志物的潜力。
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