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

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@article{c70114df06db44bca9304c446fe20c11,
title = "Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months",
abstract = "Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: These observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes.",
keywords = "Diabetes in childhood, Metabonomics, Prediction and prevention of type 1 diabetes",
author = "Overgaard, {Anne Julie} and Weir, {Jacquelyn M.} and Kaushala Jayawardana and Mortensen, {Henrik Bindesb{\o}l} and Flemming Pociot and Meikle, {Peter J.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1007/s11306-018-1456-3",
language = "English",
volume = "14",
journal = "Metabolomics",
issn = "1573-3882",
publisher = "Springer New York LLC",
number = "12",

}

RIS

TY - JOUR

T1 - Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months

AU - Overgaard, Anne Julie

AU - Weir, Jacquelyn M.

AU - Jayawardana, Kaushala

AU - Mortensen, Henrik Bindesbøl

AU - Pociot, Flemming

AU - Meikle, Peter J.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: These observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes.

AB - Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: These observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes.

KW - Diabetes in childhood

KW - Metabonomics

KW - Prediction and prevention of type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85057599059&partnerID=8YFLogxK

U2 - 10.1007/s11306-018-1456-3

DO - 10.1007/s11306-018-1456-3

M3 - Journal article

VL - 14

JO - Metabolomics

JF - Metabolomics

SN - 1573-3882

IS - 12

M1 - 158

ER -

ID: 55872700