Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
背景: 新近研究发现, 胆汁酸在调节肠道菌群代谢及包括2型糖尿病(Type 2 diabetes, T2D)在内的多种代谢异常中发挥重要作用。本研究旨在探讨血清总胆汁酸(Total bile acids, TBA)与T2D发生风险和血糖代谢指标纵向变化的相关性。 方法: 研究选取2010年基于参加社区队列调查的4968例40岁以上的非糖尿病人群, 对其进行平均4.3年的随访。所有受试者进行75 g口服糖耐量试验(Oral glucose tolerance test, OGTT), 根据1999年WHO标准诊断新发T2D。采用Cox比例风险回归模型分析血清TBA与T2D发生风险之间的相关性。检测基线及随访时受试者空腹血糖(Fasting plasma glucose, FPG)、餐后2小时血糖(2h post-loading plasma glucose, 2h PPG)及空腹血清胰岛素(Fasting serum insulin, FSI)水平。 结果: 研究人群平均21653.7人年随访, 共605例新发T2D(发病率2.8%)。与最低四分位Q1组血清TBA人群相比, Q2、Q3及Q4组人群的T2D发生风险分别增加14.2%, 15.0%及31.4 %(趋势p =0.029)。Log TBA每增加1个单位, FPG水平增高0.034 mmol/L, 2h-PPG水平增高0.111 mmol/L, log FSI水平增高0.023, log HOMA-IR水平增高0.012(p均 ≤ .024)。进一步校正基线HOMA-IR水平后, 血清TBA与T2D发生风险之间的相关性减弱。中介分析结果显示, 28.5%的TBA与T2D发生风险之间的间接作用由HOMA-IR胰岛素抵抗指数介导 (p = .0004)。 结论: 基线血清TBA水平与T2D发生风险及血糖代谢指标纵向变化呈显著正相关。胰岛素抵抗可能部分介导了TBA和T2D之间的相关性。.
Keywords: 2型糖尿病; glucose-related metabolic traits; longitudinal change; mediation analysis; prospective; serum total bile acids; type 2 diabetes; 中介分析; 前瞻性; 纵向变化; 血清总胆汁酸; 血糖代谢指标.
© 2020 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.