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Metabolomics reveals new metabolic perturbations in children with type 1 diabetes
Alfonso Galderisi1, Paola Pirillo1,2, Vittoria Moret1
1Department of Women's and Children's Health, University of Padova, Padova, Italy.
Insights
Type 1 diabetes (T1D) significantly alters children's metabolome, increasing specific hormones and metabolites. These changes may link to long-term complications, suggesting factors beyond HbA1c influence T1D
Area of Science:
- Metabolomics
- Pediatric Endocrinology
- Biochemistry
Background:
- Type 1 diabetes (T1D) is a chronic condition affecting children.
- Understanding metabolic alterations in pediatric T1D is crucial for managing long-term health.
- Previous research has not fully elucidated the urinary metabolome differences in children with T1D.
Purpose of the Study:
- To investigate the urinary metabolome of children with type 1 diabetes (T1D) compared to healthy peers.
- To explore the influence of HbA1c and clinical factors on the observed metabolic differences in pediatric T1D.
- To identify specific metabolites altered in T1D that may contribute to disease complications.
Main Methods:
- Untargeted metabolomics using liquid chromatography and mass spectrometry (LC-MS).
- Analysis of fasting urinary samples from children with T1D and matched healthy controls.
- Comparison of metabolite profiles between the two groups, correlating with clinical data.
Main Results:
- Identified 59 urinary metabolites with higher levels in children with T1D.
- Elevated metabolites included glucocorticoids, mineralocorticoids, phenylalanine and tryptophan catabolites, peptides, glycerophospholipids, fatty acids, and gut bacterial products.
- No significant association found between HbA1c, pubertal status, or disease duration and the metabolome profile within the T1D group.
Conclusions:
- Type 1 diabetes profoundly disrupts the metabolome in pediatric patients.
- Increased cortisol and aldosterone may predispose to macrovascular complications.
- Elevated tryptophan derivatives might play a role in hyperglycemia-associated neuronal damage, warranting further investigation beyond HbA1c.
Objective:
Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference.
Research Design And Methods:
We enrolled children with T1D aged 6-15 years, attending the pediatric diabetes clinic of University of Padova (Italy). Healthy controls were enrolled on voluntary basis and matched for age, sex, pubertal status, body mass index (BMI). We performed a liquid chromatography and mass spectrometry analysis (LC-MS) on fasting urinary samples of the 2 groups.
Results:
A total of 56 patients with T1D aged (11.4 ± 2.2) years, and 30 healthy controls (10.7 ± 2.8) years were enrolled. We identified 59 urinary metabolites having a higher level in children with T1D, mainly represented by gluco- and mineralcorticoids, phenylalanine and tryptophan catabolites (kynurenine), small peptides, glycerophospholipids, fatty acids, and gut bacterial products. We did not find any association between HbA1c, pubertal status, disease duration, and metabolome profile within the case group.
Conclusions:
T1D profoundly disrupts the metabolome of pediatric patients. The excess of cortisol and aldosterone may contribute to the development of macrovascular complications in adulthood, while the increase of tryptophan derivates may have a role in neuronal damage associated to hyperglycemia. Determinants of such findings, other than HbA1c, should be explored.