Abstract
IntroductionThe 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.ObjectivesWe 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.MethodsWe 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.ResultsLinear 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.ConclusionThese observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes.
Highlights
The identification of metabolomic dysregulation appears promising for the prediction of type 1 diabetes and may reveal metabolic pathways leading to beta-cell destruction
This study aimed to investigate the lipidome in relation to beta-cell function in children the first year after type 1 diabetes debut
Several lipid classes were associated with a decrease in beta-cell function after diagnosis of type 1 diabetes and the level of oxidized phosphatidylcholine could predict an increase in C-peptide over time, significance did not remain after correction for multiple testing
Summary
The identification of metabolomic dysregulation appears promising for the prediction of type 1 diabetes and may reveal metabolic pathways leading to beta-cell destruction. Within a short time after disease onset approximately half of the patients will experience a remission phase or honeymoon period characterized by endogenous insulin production and an improved glycemic control (von Herrath et al 2007) This has, been labelled by some (Muhammad et al 1999), a ‘window of opportunity’ for treatment towards preventing the further immune destruction of the beta-cells or even restoration of the beta-cells. Children progressing to type 1 diabetes before 4 years of age had lower levels of phospholipids in their cord blood (La Torre et al 2013) These observations suggest the potential of lipidomic biomarker panels in monitoring beta-cell function. We hypothesize that new biomarkers in the form of lipidomic panels in plasma from children with recent onset type 1 diabetes can predict decline or regeneration of the endogenous residual beta-cell function and may serve as markers for decline in beta-cell function before type 1 diabetes manifests clinically
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