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Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study
Benedicte Jørgenrud1,2, Lars C Stene3, German Tapia3
1Department of Pediatric Research, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
Insights
This study tracked infant metabolic profiles, finding age-related changes in plasma metabolites. Breastfeeding duration influenced levels of specific amino acids and fatty acids, potentially impacting type 1 diabetes risk.
Area of Science:
- Metabolomics
- Pediatrics
- Immunology
Background:
- Type 1 diabetes (T1D) is an autoimmune disease with early-life origins.
- Understanding metabolic changes in infants is crucial for identifying T1D risk factors.
- Longitudinal studies are needed to track metabolic profiles from infancy.
Purpose of the Study:
- To investigate longitudinal plasma metabolic profiles in healthy infants.
- To explore associations between metabolic profiles, breastfeeding duration, and islet autoantibodies.
- To identify potential early biomarkers for type 1 diabetes.
Main Methods:
- Analyzed longitudinal plasma samples from infants (n=58) using 2D-GC-TOF-MS.
- Focused on small polar metabolites in infants with and without islet autoimmunity.
- Controlled for age, sex, and HLA genotype (DR4-DQ8/DR3-DQ2).
Main Results:
- Plasma metabolite levels significantly changed with age (3-24 months).
- No significant differences in tyrosine or ornithine levels between case and control infants after multiple testing correction.
- Breastfeeding ≥3 months associated with higher isoleucine and lower methionine/3,4-dihydroxybutyric acid at 3 months.
Conclusions:
- Infant plasma metabolite levels change with age, irrespective of later islet autoimmunity.
- Breastfeeding duration is linked to distinct metabolic profiles in early infancy.
- Metabolic profiling may offer insights into T1D pathogenesis and prevention strategies.
Aims:
The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.
Method:
Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.
Results:
Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.
Conclusions:
Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.
