State Key Laboratory of Medical Genomics, Shanghai National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Diabetes. 2020 Aug;12(8):616-625. doi: 10.1111/1753-0407.13040. Epub 2020 Apr 15.
Bile acids have been found to be related to changes in gut microbiota and multiple metabolic disorders, including type 2 diabetes (T2D). We aimed to prospectively investigate associations of serum total bile acids (TBAs) with risk of incident T2D and longitudinal changes in glycemic traits.
A community-based study was conducted at baseline in 2010, including 4968 nondiabetic participants aged ≥40 years followed up for an average of 4.3 years. Incident T2D was defined by using the 1999 WHO criteria based on 75-g oral glucose tolerance tests. Multivariate Cox proportional hazards regression was used to examine the association of serum TBAs with incident T2D. Fasting plasma glucose (FPG), 2-hour postload plasma glucose (2-h PPG), and fasting serum insulin (FSI) were measured at baseline and follow-up.
During 21 653.7 person-years of follow-up, 605 cases of incident diabetes were identified (incidence rate 2.8%). Comparing to quartile 1 of serum TBAs, quartile 2, 3, and 4 were significantly associated with a 14.2%, 15.0%, and 31.4% higher risk of incident T2D (P = .029). Each one unit of log-TBAs was associated with an increase of 0.034 mmol/L in FPG, 0.111 mmol/L in 2-h PPG, 0.023 in log-FSI, and 0.012 in log-HOMA-IR (homeostasis model assessment of insulin resistance) (all P ≤ .024). The association was attenuated after further adjustment for HOMA-IR. Mediation analysis showed that insulin resistance indicated by HOMA-IR might mediate 28.5% of indirect effect on the association of TBAs with T2D (P = .0004).
Baseline serum TBAs were significantly associated with incident T2D and longitudinal changes in glycemic traits. Insulin resistance might partially mediate the association of TBAs and T2D.
已发现胆汁酸与肠道微生物群的变化和多种代谢紊乱有关，包括 2 型糖尿病（T2D）。我们旨在前瞻性研究血清总胆汁酸（TBAs）与 T2D 发病风险和血糖特征的纵向变化之间的关联。
2010 年在基线进行了一项基于社区的研究，包括 4968 名年龄≥40 岁的非糖尿病参与者，平均随访 4.3 年。根据 75g 口服葡萄糖耐量试验，采用 1999 年世卫组织标准定义新发 T2D。使用多变量 Cox 比例风险回归来检查血清 TBAs 与新发 T2D 的相关性。在基线和随访时测量空腹血糖（FPG）、餐后 2 小时血糖（2-h PPG）和空腹血清胰岛素（FSI）。
在 21653.7 人年的随访期间，确定了 605 例新发糖尿病病例（发病率 2.8%）。与 TBAs 血清四分位 1 相比，四分位 2、3 和 4 与 T2D 发病风险分别增加 14.2%、15.0%和 31.4%（P=0.029）。TBAs 对数每增加 1 个单位，FPG 增加 0.034mmol/L，2-h PPG 增加 0.111mmol/L，FSI 对数增加 0.023，HOMA-IR（胰岛素抵抗评估的稳态模型）对数增加 0.012（所有 P≤0.024）。进一步调整 HOMA-IR 后，相关性减弱。中介分析表明，HOMA-IR 所表示的胰岛素抵抗可能部分介导了 TBAs 与 T2D 之间关联的间接作用（P=0.0004）。
基线血清 TBAs 与 T2D 发病和血糖特征的纵向变化显著相关。胰岛素抵抗可能部分介导了 TBAs 与 T2D 之间的关联。
