Fig. 4: Association between palmitic acid and atherosclerotic plaque vulnerability in T2DM.

A Orthogonal partial least squares discriminant analysis (OPLS-DA) scatter plot demonstrates the metabolomic differences between non-T2DM and T2DM human serum samples. B Cross-validation plot for the OPLS-DA model reveals model robustness and absence of overfitting, as validated by the intercepts of R2 = (0.0, 0.891) and Q2 = (0.0, 0.367). C Volcano plot detailing the results of pairwise comparisons of metabolites in T2DM relative to non-T2DM subjects. D Venn diagram displays the overlap of 705 annotated metabolites shared between human and mouse models. E Display of the top 30 altered metabolites, ranked by their log2 fold change. F Metabolite annotation using the Lipid Maps database. G Visualization of significantly altered metabolites annotated by Lipid Maps database. H Venn diagram shows the 34 shared human-mouse annotated metabolites classified within the “Fatty acyls” category according to the Lipid Maps database. Depiction of the count of distinctively altered metabolites across categories (I) and within “Fatty acyls” category (J). K Visualization of significantly altered metabolites in the “Fatty acyls” category. L Comparison of serum palmitic acid (PA) concentration between non-T2DM and T2DM human subjects. (n = 55 subjects in non-T2DM and n = 46 subjects in T2DM, data presented as mean ± SD, two-tailed unpaired Student t-test with Welch’s correction, ***P < 0.001). M Two-tailed Pearson’s linear regression analysis shows a significant negative correlation (r = −0.262, P = 0.008) between serum PA concentration and coronary plaque fibrous cap thickness. The shaded area around the regression line is the error band, representing confidence interval. N Logistic regression analysis reveals the relationship between PA and plaque vulnerability in the cohort study. Model 1 indicates the univariate regression analysis; Model 2 is adjusted for age and gender; Model 3 is adjusted for age, gender, BMI, LDL, smoking, and hypertension. (The center for the error bars is the point estimate of the odds ratio for each variable. n = 101 subjects). O A Kaplan-Meier survival curve plots the 180-day MACE-free survival in Higher PA group versus Lower PA group. Source data are provided as a Source Data file.