Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA.
Department of Nutrition Harvard T.H. Chan School of Public Health Boston MA USA.
J Am Heart Assoc. 2024 Aug 6;13(15):e033350. doi: 10.1161/JAHA.123.033350. Epub 2024 Jul 18.
Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3.
We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, =0.02; saliva: 13.3±5.11, =0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, =0.02) and triglyceride (0.52±0.18, =0.002).
Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.
队列研究的证据表明,牙周病和 2 型糖尿病(T2D)之间存在双向关系,但潜在机制尚不清楚。在这项研究中,我们旨在(1)确定与牙周病相关的唾液、血浆和多流体代谢组学特征,(2)确定这些特征是否可预测 3 年内 T2D 的进展和心血管代谢生物标志物。
我们纳入了 SOALS(圣胡安超重成人纵向研究)(n=911)的参与者。使用液相色谱-质谱法对唾液(k=635)和血浆(k=1051)中的代谢物进行定量。我们应用 10 倍交叉验证的弹性网络回归来识别牙周病的基线代谢组学特征。多变量 Cox 比例风险回归和线性回归用于评估与 T2D 进展和生物标志物浓度的关联。代谢组学特征包括与赖氨酸和嘧啶代谢高度相关的加权代谢物。牙周病或其 3 个代谢组学特征与 3 年内 T2D 的进展无关。前瞻性地,多流体和唾液代谢组学特征的 1-SD 增加与较低的低密度脂蛋白(多流体:12.9±5.70,=0.02;唾液:13.3±5.11,=0.009)相关。血浆代谢组学特征的 1-SD 增加也与稳态模型评估的胰岛素抵抗(2.67±1.14,=0.02)和甘油三酯(0.52±0.18,=0.002)相关。
尽管牙周病的代谢组学特征不能预测 T2D 的进展,但它们与第 3 年的低密度脂蛋白、甘油三酯和稳态模型评估的胰岛素抵抗水平相关。