1450-P: Differential Regulation of Noncanonical (Deoxy- and Deoxymethyl-) Sphingolipids Biosynthesis in Type 1 and Type 2 Diabetes Mellitus

Introduction and Objective: Deoxy- and deoxymethyl-sphingolipids (m18:1 and m17:1) are two classes of sphingolipids (SLs) resulting from the condensation of palmitoyl-CoA with alanine or glycine respectively, instead of serine. Due to their structure, they evade normal catabolic routes, favoring cellular accumulation and lipotoxicity. Recent studies have highlighted the role of deoxySLs in the pathophysiology of type 2 diabetes (T2D). The aim of this study was to compare the concentrations of circulating deoxySLs in type 1 diabetes (T1D) and T2D as compared to healthy individuals. Methods: Sphingolipidomic profiles of 15 plasma samples from T1D patients, T2D patients and healthy controls (HC) (age, sex and BMI matched, n. 45 subjects) were analyzed by targeted LC/MS-MS. Statistical analysis was performed by ANOVA test. Results: Total ceramides concentrations were significantly decreased in T1D (p0.005) and Cer 18:0/Cer 24:0 ratio, a metabolic and cardiovascular risk marker, was significantly lower in T1D compared to T2D (p0.005). Glucosyl ceramides (HexCer) were reduced in T2D as compared to HC, while in T1D only HexCer 16:0 and 18:0 were significantly decreased as compared to HC (both p0.05). Total contents of deoxyCers and deoxyDHCers were elevated in T2D, and significantly reduced in T1D, as compared to both HC (p0.05) and T2D (p0.001). DeoxymethylSLs showed a similar trend as deoxySLs, though their changes were not as marked. Sphingosine-1-phosphate levels did not differ between HC and T1D and T2D, showing no significant changes in the catabolism of canonical SLs. Conclusion: There is a differential regulation of the biosynthesis and the degradation in canonical SLs (d18:1) between T1D and T2D. Interestingly, no significant differences were found between T2D and HC. DeoxySLs were increased in T2D and decreased in T1D, as compared to controls, and could be markers of differential effects of insulin resistance, hyperglycemia and lack of endogenous insulin secretion between T1D and T2D in these processes. Disclosure L. Centofanti: None. C. Morano: None. M. Dei Cas: None. P. Zermiani: None. U. Mortola: None. M. Bignotto: None. G. Serrao: None. P. Battezzati: None. R. Paroni: None. F. Folli: None. Funding Project PNC 0000001 D3 4 Health, - CUP B83C22006120001, The National Plan for Complementary Investments to the NRRP, Funded by the European Union – NextGenerationEU.