Preliminary Comparative Analysis of Circulatory Glycosaminoglycan Concentrations and Disaccharide Profiles in Diabetic and Healthy Subjects

Background: Type II diabetes (T2D) represents a significant global health challenge, necessitating deeper insights into its complex disease mechanism. While numerous efforts have advanced the understanding and treatment of T2D, the role of circulating glycosaminoglycans (GAGs) in diabetic plasma remains unclear. This study provides preliminary quantitative and qualitative screening of circulating GAG macromolecule levels in diabetic vs. healthy plasma. Methods: Plasma samples were collected from healthy and diabetic individuals (n = 12 per group). Then, via disaccharide composition liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, the GAG species was quantified and their disaccharide profiles were evaluated. Results: Notably, a significant reduction in the relative abundance of the chondroitin sulfate (CS) 2S6S disaccharide was also observed (P = .004). Additionally, CS concentrations in healthy human plasma were approximately 70 and 100 times higher than those of hyaluronic acid (HA) and heparan sulfate (HS), respectively, highlighting differential enzymatic or nonenzymatic turnover rates among GAG species. Interestingly, circulating CS, HS, and HA levels remained stable in diabetic plasma. Conclusion: These findings elucidate the downregulation of a specific disaccharide variant (CS 2S6S) as a potential biomarker of T2D. Further research is warranted to elucidate the mechanistic underpinnings of these observations and their clinical implications.