Type 2 diabetes (T2D) and prediabetes represent a progressive glycemic continuum associated with multi-pathway metabolic deterioration that often precedes clinical diagnosis. Early identification of molecular alterations underlying this transition is critical for prevention strategies. Untargeted gas chromatography–mass spectrometry (GC–MS) metabolomics combined with multivariate statistical analysis (PCA) was applied to serum samples from 188 participants stratified into Control (n = 48), Prediabetes (n = 113), and Diabetes (n = 27) groups according to ADA/WHO diagnostic criteria. Progressive metabolic alterations were observed across the glycemic continuum. Several amino acid-, lipid-, and organic acid-related features showed nominal differences between the study groups. However, none of the detected metabolomic features remained statistically significant after false discovery rate (FDR) correction, indicating that these findings should be considered exploratory. Diabetes was associated with widespread downregulation of amino acid-related features, long-chain and complex lipid species, and small organic acids relative to both control and prediabetes groups. PCA (PC1 = 35.9%) showed progressive metabolic stratification primarily driven by hyperglycemia, dyslipidemia, and blood pressure elevation. These exploratory findings suggest that the transition from prediabetes to diabetes may be accompanied by alterations in amino acid, lipid, and energy metabolism. The identified metabolomic features represent candidate metabolites that require validation in larger independent cohorts using targeted metabolomics.

Population-specific data on serum fatty acids across the progression to type 2 diabetes mellitus (T2DM) are limited. In this exploratory cross-sectional study, serum fatty acids were determined by gas chromatography–mass spectrometry in 177 adults from Kazakhstan (45 normoglycemic, 114 with prediabetes, 18 with T2DM) and expressed as percentages of the quantified profile of the 13 components detected in ≥50% of samples. No fatty acid differed between glycemic groups after false discovery rate correction. In controls and participants with prediabetes, oleic and palmitoleic acids correlated with serum triglycerides (ρ = +0.65 and +0.32; q ≤ 0.005), and both associations persisted after adjustment for age, sex and adiposity and after exclusion of implausible profiles arising from a peak-assignment inconsistency. Across all participants, linoleic acid correlated inversely with glycated hemoglobin (HbA1c; ρ = −0.21, q = 0.033) in unadjusted analyses only. An association of heptadecanoic acid with HbA1c depended on its non-detection in part of the samples and was neither established nor excluded. Covariates were not recorded for the T2DM group, HbA1c was recorded with limited precision for most participants, and adjusted analyses were restricted to 107 participants without diabetes. The study describes serum fatty acid composition in this population and generates hypotheses.