The research involved 360 participants: 91 with T1D, 91 with T2D, 74 prediabetic individuals, and 104 controls. All participants were free from previous cardiovascular or chronic kidney disease. The study utilized untargeted lipidomic analysis through Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) to assess lipid profiles. Multiple linear regression models were employed to examine the associations of different lipid classes with diabetes, while considering both sex-specific differences and glycemic states.

 Study findings

 The study identified 54 unique lipid subspecies from 15 unique lipid classes, highlighting a diverse lipidomic profile associated with diabetes.

Lysophosphatidylcholines (LPC) and ceramides showed opposite effects in subjects with T1D and subjects with T2D. Lysophosphatidylcholines were significantly up-regulated in T1D participants but down-regulated in those with T2D. This suggests that LPC metabolism differs markedly between these two types of diabetes. This increase in LPC levels may correlate with increased LCAT activity, which is involved in lipid metabolism, particularly the synthesis of phosphocholine and cholesteryl esters from LPCs and phosphatidylcholine.

Ceramides displayed the opposite trend compared to LPCs; they were found to be up-regulated in subjects with T2D while showing down-regulation in T1D. Variants such as 1-deoxyceramides exhibited a significant increase in T2D, marking them as important indicators of the disease. These findings indicate a clear alteration in ceramide metabolism in type 2 diabetes that may influence insulin signaling pathways, potentially worsening insulin resistance.

Phosphatidylcholines (PC) were predominantly down-regulated in the subjects with type 1 diabetes; this may have implications for membrane integrity and function. This down-regulation contributes to the overall altered lipid profile observed in T1D.

Interestingly, the study identified sex-specific lipidomic differences. For instance, lipid alterations were notably more pronounced in men regarding certain ceramides. Specifically, specific ceramide molecules were significantly decreased only in men with T1D. Additionally, higher levels of phosphatidylcholines were present in normoglycemic women than in men. These findings point to the role of hormonal factors in determining sex-specific lipid metabolism differences.

We also analyzed possible associations of lipid classes with the glycemic state, i.e. normoglycemia, prediabetes and type 2 diabetes. A gradual increase in 1-deoxyceramides was seen progressing from normoglycemia through prediabetes to T2D, indicating these lipid species might serve as potential early biomarkers for diabetes progression.

Clinical and research implications

 The findings underscore a substantial disruption in lipid metabolism for both types of diabetes, indicating that further investigation into lipidomic profiles may yield critical insights into diabetes pathophysiology. This could lead to enhanced understanding of the disease mechanisms and the identification of novel biomarkers for diabetes. Furthermore, from the clinical point of view, our results suggest the need for sex-specific strategies in diabetes management. This personalized approach to treatment could enhance patient outcomes and open avenues for tailored therapeutic interventions. Moreover, the future potential introduction of lipidomic profiling characterization into routine clinical assessments could contribute to more precise management of diabetes and its complications.

Overall, this study contributes relevant knowledge to the field of diabetes research, emphasizing the potential of lipidomics in personalizing treatment strategies while highlighting the importance of sex differences in metabolic responses.