Novel Plasma Metabolomic Markers Associated with Diabetes Progression in Older Puerto Ricans

Abstract

We assessed longitudinal associations between plasma metabolites, their network-derived clusters, and type 2 diabetes (T2D) progression in Puerto Rican adults, a high-risk Hispanic subgroup with established health disparities. We used data from 1221 participants free of T2D and aged 40-75 years at baseline in the Boston Puerto Rican Health and San Juan Overweight Adult Longitudinal Studies. We used multivariable Poisson regression models to examine associations between baseline concentrations of metabolites and incident T2D and prediabetes. Cohort-specific estimates were combined using inverse-variance weighted fixed-effects meta-analyses. A cluster of 13 metabolites of branched chain amino acids (BCAA), and aromatic amino acid metabolism (pooled IRR = 1.87, 95% CI: 1.28; 2.73), and a cell membrane component metabolite cluster (pooled IRR = 1.54, 95% CI: 1.04; 2.27) were associated with a higher risk of incident T2D. When the metabolites were tested individually, in combined analysis, 5 metabolites involved in BCAA metabolism were associated with incident T2D. These findings highlight potential prognostic biomarkers to identify Puerto Rican adults who may be at high risk for diabetes. Future studies should examine whether diet and lifestyle can modify the associations between these metabolites and progression to T2D.

Keywords: Hispanic; biomarkers; diabetes; metabolites.

Figure 1

(A) Distribution of San Juan Overweight Adult Study (SOALS) participants at follow-up, according to baseline glycemic levels. (B) Distribution of Boston Puerto Rican Health Study (BPRHS) participants at follow-up, according to baseline glycemic levels.

Figure 1

(A) Distribution of San Juan Overweight Adult Study (SOALS) participants at follow-up, according to baseline glycemic levels. (B) Distribution of Boston Puerto Rican Health Study (BPRHS) participants at follow-up, according to baseline glycemic levels.

Figure 2

(A) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among all participants, according to their network-derived pathway. (B) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among those with prediabetes at baseline, according to their network-derived pathway. (C) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident prediabetes among participants with normal glycemic levels at baseline, according to their network-derived pathway. (D) Incidence rate ratios (IRR) and p-values (P) for individual metabolites in relation to incident prediabetes or type 2 diabetes among all participants, according to their network-derived pathway. Metabolites with unadjusted p-values < 0.05 are colored according to their network-derived cluster membership; metabolites with FDR-adjusted p-values < 0.05 are indicated with a triangle-shaped marker.

Figure 2

(A) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among all participants, according to their network-derived pathway. (B) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among those with prediabetes at baseline, according to their network-derived pathway. (C) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident prediabetes among participants with normal glycemic levels at baseline, according to their network-derived pathway. (D) Incidence rate ratios (IRR) and p-values (P) for individual metabolites in relation to incident prediabetes or type 2 diabetes among all participants, according to their network-derived pathway. Metabolites with unadjusted p-values < 0.05 are colored according to their network-derived cluster membership; metabolites with FDR-adjusted p-values < 0.05 are indicated with a triangle-shaped marker.

Figure 2

(A) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among all participants, according to their network-derived pathway. (B) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident type 2 diabetes among those with prediabetes at baseline, according to their network-derived pathway. (C) Incidence rate ratios (IRR) and unadjusted p-values (P) for individual metabolites in relation to incident prediabetes among participants with normal glycemic levels at baseline, according to their network-derived pathway. (D) Incidence rate ratios (IRR) and p-values (P) for individual metabolites in relation to incident prediabetes or type 2 diabetes among all participants, according to their network-derived pathway. Metabolites with unadjusted p-values < 0.05 are colored according to their network-derived cluster membership; metabolites with FDR-adjusted p-values < 0.05 are indicated with a triangle-shaped marker.