Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

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.

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.

Hispanic adults with type 2 diabetes mellitus using lipid-lowering agents have better periodontal health than non-users.

Background: Recent studies suggest that lipid-lowering agents (LLA) may reduce chronic periodontitis, but it is unknown whether this benefit extends to people with type 2 diabetes (T2D). Objective: We assessed the association between LLA use and periodontitis in Hispanic adults with T2D. Design: This was a cross-sectional observational study. Methods: We assessed the association of LLA use and periodontal parameters in 253 Puerto Ricans 40-65 years with T2D who participated in the Lipid-Lowering agents use in Periodontitis and Diabetes Study study. Participants were classified as (a) none- or <1 year, (b) 1-4 years, or (c) >4 years. The primary outcome consists of a tertile percent of sites with probing pocket depth (PPD) ⩾ 4 mm and the secondary outcome includes tertiles of percent sites with clinical attachment loss (CAL) ⩾ 4 mm. Multinomial logistic regression models adjusted for age, gender, smoking status, education, waist circumference, glycosylated hemoglobin A1C (HbA1c), bleeding on probing, examiner, and anti-inflammatory agents were used to estimate the association. Results: LLA (92.5%, statins) was used by 52% of participants. LLA use 1-4 years was associated with lower odds of PPD ⩾ 4 mm (OR: 0.22, p = 0.005; high versus low tertile) or lower odds of CAL ⩾ 4 mm (OR: 0.33, p = 0.02, middle versus low tertile), compared to those with LLA minimal or no use. This association was lost for participants who used LLA for >4 years. LLA users for >4 years with periodontal disease had elevated HbA1c (OR: 1.36, p = 0.05). Conclusion: The use of LLA for 1-4 years was associated with lower values of periodontal parameters versus minimal LLA use. This association was not present among people using LLA > 4 years users, but these participants had poorer glycemic control compared to other participants. In this cross-sectional study, the finding that LLA use 1- 4 years is associated with lower values of periodontal parameters of severity in T2D individuals may help clarify some of the controversies regarding the benefit of these medications in this population.

Lipid-lowering agents and lower values of periodontal parameters in individuals with type 2 diabetes • Lipid-lowering agents (LLA), such as statins, are reported to reduce chronic periodontitis, making individuals with diabetes ideal candidates for this treatment due to their high prevalence of oral disease.• The association between LLA use and periodontitis was assessed among Hispanic adults with type 2 diabetes (T2D).• Short-term LLA use (but not long-term use) was associated with lower values of periodontal parameters in individuals with T2D.• For long-term LLA use, high glycemic level was associated with high values of periodontitis.• Thus, under the study design limitations, the finding may provide clinical implications and may help clarify some of the controversies regarding the benefits of LLA use in humans.• Furthermore, the higher glycemic levels for periodontal patients with long-term LLA use points to the need to monitor these patients carefully.