Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months

The identification of metabolomic dysregulation appears promising for the prediction of type 1 diabetes and may also reveal metabolic pathways leading to beta-cell destruction. Recent studies indicate that regulation of multiple phospholipids precede the presence of autoantigens in the development of type 1 diabetes.

We hypothesize that lipid biomarkers in plasma from children with recent onset type 1 diabetes will reflect their remaining beta-cell function and predict future changes in beta-cell function.

We performed targeted lipidomic profiling by electrospray ionization tandem mass spectrometry to acquire comparative measures of 354 lipid species covering 25 lipid classes and subclasses in plasma samples from 123 patients < 17 years of age followed prospectively at 1, 3, 6 and 12 months after diagnosis. Lipidomic profiles were analysed using liner regression to investigate the relationship between plasma lipids and meal stimulated C-peptide levels at each time point. P-values were corrected for multiple comparisons by the method of Benjamini and Hochberg.

Linear regression analysis showed that the relative levels of cholesteryl ester, diacylglycerol and triacylglycerol at 1 month were associated to the change in c-peptide levels from 1 to 6 months (corrected p-values of 4.06E-03, 1.72E-02 and 1.72E02, respectively). Medium chain saturated and monounsaturated fatty acids were the major constituents of the di- and triacylglycerol species suggesting a link with increased lipogenesis.

These observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes.