Oxidized metabolites of linoleic acid as biomarkers of pancreatic beta-cell function in the first-onset type 2 diabetic patients with obesity.

OBJECTIVES

The role of oxylipins in type 2 diabetes (T2D) with obesity remains poorly understood. This study aimed to characterize oxylipin profiles in T2D patients with obesity, identify associations with pancreatic beta-cell function, and suggest potential therapeutic targets.

METHODS

We recruited first-onset T2D patients with obesity (OB group, n = 15) and normal-weight T2D patients (NW group, n = 15), matched by gender, age, and blood lipid levels. Serum samples were collected in a fasting state before medication. Oxylipin profiling was analyzed using liquid chromatography-tandem mass spectrometry, detecting 120 oxylipins. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze oxylipin profiles, and Pearson’s correlation coefficients assessed the relationship between oxylipin concentrations and clinical parameters.

RESULTS

Six oxylipins with variable importance in projection (VIP > 1) and p < 0.05 were significantly different between OB and NW groups. Five oxylipins (13-oxoODE, 12,13-EpOME, 15-keto-PGE2, 9,10-EpOME, 16(17)-EpDPE) were elevated in the OB group, while 2,3-dinor-8-iso-PGF2α was reduced. Correlation analysis revealed that 13-oxoODE, 15-keto-PGE2, and 16(17)-EpDPE levels positively correlated with BMI, visceral adipose tissue (VAT), and pancreatic beta-cell function.

CONCLUSIONS

Oxylipin profiling in first-onset T2D patients with obesity revealed that altered oxylipin metabolism, particularly linoleic acid pathways, is closely linked to pancreatic beta-cell dysfunction. These findings suggest potential biomarkers for therapeutic intervention.