Association of Serum Bile Acids Profile and Pathway Dysregulation With the Risk of Developing Diabetes Among Normoglycemic Chinese Adults: Findings From the 4C Study
Association of Serum Bile Acids Profile and Pathway Dysregulation With the Risk of Developing Diabetes Among Normoglycemic Chinese Adults: Findings From the 4C Study
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血清胆汁酸谱和通路失调与血糖正常的中国成年人患糖尿病风险的关系：4C 研究的结果
DOI：
10.2337/dc20-0884
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发表时间：
2021-02-01
期刊：
影响因子：
16.2
通讯作者：
Wang, Weiqing
中科院分区：
文献类型：
--
作者：
Lu, Jieli;Wang, Shuangyuan;Wang, Weiqing
目的对糖尿病患者发病前血清胆汁酸(BAS)异常进行综合评估，目前尚无定论。在血糖正常的中国成年人中，我们研究了血清BA谱和协同调节与发生2型糖尿病(T2 DM)风险的关系。研究设计与方法我们检测了中国心脏代谢性疾病与癌症队列(4C)研究中与倾向性评分(包括年龄、性别、体重指数和空腹血糖)匹配的23种BA在糖尿病患者(n=1,707)和对照组(n=1,707)中的水平。用条件Logistic回归方法估计BAS与T2 DM关联的多变量调整优势比(ORs)。结果在多因素Logistic回归分析中，原、继发性未结合胆酸的单位标准差增量与糖尿病发病呈负相关，胆酸、鹅去氧胆酸和去氧胆酸的OR(95%CI)分别为0.89(0.83~0.96)、0.90(0.84~0.97)和0.90(0.83~0.96)(P<；0.05和假发现率均为0.05)。而一级BAs(甘胆酸、牛磺胆酸、甘鹅脱氧胆酸、牛磺鹅去氧胆酸、硫酸甘鹅脱氧胆酸)和继发性BA(牛磺熊去氧胆酸)与糖尿病发病呈正相关，OR值为1.11~1.19(95%Cis为1.05~1.28)。在完全调整的模型中，另外调整了肝酶、高密度脂蛋白胆固醇、饮食、2小时后血糖、HOMA-胰岛素抵抗和腰围，风险估计是相似的。差分相关网络分析显示，类内(即初级和次级)和类间(即非共轭和共轭)BA共调节的扰动在糖尿病发病前就已经存在。结论这些发现揭示了T2 DM发病前BAS的新变化，支持BA代谢在糖尿病发病机制中的潜在作用。
OBJECTIVE Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83–0.96) for cholic acid, 0.90 (0.84–0.97) for chenodeoxycholic acid, and 0.90 (0.83–0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.