Saliva, Plasma, and Multifluid Metabolomic Signatures of Periodontal Disease, Type 2 Diabetes Progression, and Markers of Glycemia and Dyslipidemia Among Puerto Rican Adults With Overweight and Obesity

Abstract

Background: 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.

Methods and results: 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, P=0.02; saliva: 13.3±5.11, P=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, P=0.02) and triglyceride (0.52±0.18, P=0.002).

Conclusions: 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.

Keywords: T2D progression; metabolomics; periodontal disease; plasma metabolites; saliva metabolites; type 2 diabetes.

Figure 1. Venn diagram of the numbers of metabolites identified by the plasma, saliva, and multifluid metabolomic profiles of periodontal disease.*

*The circle on the upper left corner represents the number of metabolites selected in the multifluid metabolomic profile: 11 unique, 28 in common with the plasma profile, and 30 in common with the saliva profile. The circle on the upper right corner represents the number of metabolites selected in the plasma metabolomic profile, which has 11 unique metabolites and 2 in common with the saliva metabolomic profile. The circle on the bottom represents the saliva metabolomic profile, which has 21 unique metabolites. One metabolite (N,N‐dimethyl‐5‐aminovalerate) is common in all 3 signatures. The saliva and multifluid profiles share 30 common metabolites. The plasma and multifluid profiles share 28 common metabolites. The plasma and saliva profiles share 2 common metabolites.