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Sardinian Infants of Diabetic Mothers: A Metabolomics Observational Study
Angelica Dessì1, Alice Bosco1, Flaminia Cesare Marincola2
1Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, 09042 Cagliari, Italy.
Insights
Newborns of mothers with gestational diabetes mellitus (GDM) who received insulin therapy showed distinct urinary metabolic profiles at birth. These early biomarkers may help monitor infants and predict future chronic disease risk.
Area of Science:
- Metabolomics
- Neonatal Health
- Endocrinology
Background:
- Gestational diabetes mellitus (GDM) presents risks for fetal and neonatal well-being.
- Uncontrolled GDM can lead to long-term health issues in offspring, including obesity and type 2 diabetes.
- Identifying early biomarkers in newborns of diabetic mothers (NDMs) is crucial for monitoring and early diagnosis.
Purpose of the Study:
- To analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) using NMR and GS-MS.
- To identify potential biomarkers for monitoring NDMs and predicting chronic disease predisposition.
- To compare metabolomic profiles between infants of mothers receiving diet therapy versus insulin therapy, and controls.
Main Methods:
- Utilized nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS).
- Analyzed urine samples from 26 newborns (21 NDMs, 5 controls) at five time points from birth to six months postpartum.
- NDMs were categorized into diet therapy (NDM-diet) and insulin therapy (NDM-insulin) groups.
Main Results:
- At birth (T1), significant variations in seven urinary metabolites were observed in NDM-insulin infants compared to NDM-diet and control infants.
- Altered metabolites included acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine, and N-carbamoyl-aspartate.
- These metabolic changes were linked to pathways like citrate, glycine, serine, threonine, arginine, proline, amino sugar, nucleotide sugar, and pyruvate metabolism, but were not present at later time points.
Conclusions:
- Specific urinary metabolic profiles at birth in infants of mothers with GDM on insulin therapy may serve as early indicators.
- These findings suggest potential biomarkers for monitoring and early diagnosis of chronic disease risk in these infants.
- Early nutrition (maternal and formula) is considered a potential factor influencing these early metabolomic differences.
Abstract:
Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An uncontrolled GDM can lead to an increased risk of morbidity in the fetus and newborn, and an increased risk of obesity or developing type 2 diabetes, hypertension or neurocognitive developmental impairment in adulthood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS) to analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) with the aim of identifying biomarkers useful for the monitoring of NDMs and for early diagnosis of predisposition to develop related chronic diseases. A total of 26 newborns were recruited: 21 children of diabetic mothers, comprising 13 in diet therapy (NDM-diet) and 8 in insulin therapy (NDM-insulin), and 5 control children of non-diabetic mothers (CTR). Urine samples were collected at five time points: at birth (T1), on the third day of life (T2), one week (T3), one month (T4) and six months postpartum (T5). At T1, variations were observed in the levels of seven potential biomarkers (acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine and N-carbamoyl-aspartate) in NMD-insulin infants compared to NDM-diet and CTR infants. In particular, the altered metabolites were found to be involved in several metabolic pathways such as citrate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism, and pyruvate metabolism. In contrast, these changes were not visible at subsequent sampling times. The impact of early nutrition (maternal and formula milk) on the metabolomic profile was considered as a potential contributing factor to this finding.
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