Feng Su-Su, Wang Si-Jing, Guo Lin, Ma Pan-Pan, Ye Xiao-Long, Pan Ming-Lin, Hang Bo, Mao Jian-Hua, Snijders Antoine M, Lu Yi-Bing, Ding Da-Fa
Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China.
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States.
World J Diabetes. 2024 May 15;15(5):898-913. doi: 10.4239/wjd.v15.i5.898.
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.
To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.
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.
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.
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.
在2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)的个体中,对胆汁酸(BA)和不饱和脂肪酸(UFA)谱及其失调的理解仍然不清楚。研究这些代谢物可为T2DM中NAFLD的病理生理学提供有价值的见解。
确定能够区分NAFLD和T2DM的潜在代谢物生物标志物。
开发了一个训练模型,涉及399名参与者,包括113名健康对照者(HC)、134名无NAFLD的T2DM患者和152名患有T2DM和NAFLD的患者。外部验证包括172名参与者。NAFLD患者根据肝纤维化评分进行分组。分析方法采用单变量测试、正交偏最小二乘判别分析、逻辑回归、受试者工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。
与HC相比,T2DM组和NAFLD组的特定BA水平均降低。在UFA中,特定的酸与T2DM中NAFLD的风险呈正相关,而ω-6:ω-3 UFA比率呈负相关。α-亚麻酸和γ-亚麻酸的水平与NAFLD中的显著肝纤维化有关。验证队列证实了这些生物标志物在评估T2DM患者NAFLD风险方面的预测效力。
本研究强调了BA和UFA谱改变与T2DM个体中NAFLD存在之间的联系,提出它们作为NAFLD发病机制中生物标志物的潜力。