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Author Spotlight: Assessing the Cardiovascular Profile of Patients with Metabolic Syndrome
Published on: September 27, 2024
Cardiometabolic disease risk markers are increased following burn injury in children
Sofina Begum1,2,3,4,5, Samantha Lodge4, Drew Hall4
1Harvard Medical School, Harvard University, Boston, MA, United States.
Insights
Pediatric burn survivors exhibit a lasting "metabolic memory" with altered immune and metabolic functions, increasing long-term cardiovascular disease risk. This highlights the need for ongoing cardiometabolic health monitoring in children post-burn.
Area of Science:
- Pediatric medicine
- Metabolomics
- Immunology
Background:
- Pediatric burn injuries cause significant, long-term systemic physiological and metabolic disturbances.
- The precise metabolic trajectory and long-term health outcomes following childhood burns remain incompletely understood.
Purpose of the Study:
- To comprehensively evaluate the chronic immuno-metabolic consequences of pediatric burn injury.
- To identify specific metabolic signatures and altered pathways persisting years after burn trauma.
Main Methods:
- Employed a multi-platform strategy analyzing plasma metabolites, lipoproteins, and cytokines using 1H Nuclear Magnetic Resonance (NMR) spectroscopy.
- Collected plasma samples from 36 pediatric burn survivors (aged 4-8 years) and 21 healthy controls, 3 years post-injury.
- Utilized Metabolite Correlation Network Analysis to explore interrelationships between immune and metabolic markers.
Main Results:
- Burn survivors displayed signatures of hyperglycemia, hypermetabolism, and inflammation, impacting glycolysis, the TCA cycle, and amino acid/urea metabolism.
- Significant alterations in lipoprotein profiles were observed, including reduced very-low-density lipoprotein sub-components and elevated small-dense low-density lipoprotein particles.
- A striking increase in correlations between cytokines, lipoproteins, and metabolites was noted in burn-injured children, indicating a perturbed immuno-metabolic network.
Conclusions:
- Pediatric burn injury establishes a persistent
- metabolic memory
- characterized by interconnected immune and metabolic dysregulation.
- These chronic metabolic changes, independent of burn severity, are associated with an increased long-term risk of cardiovascular disease.
- Emphasizes the critical need for enhanced, long-term cardiometabolic health surveillance in pediatric burn survivors.
Introduction:
Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes.
Methods:
A multi-platform strategy was implemented to evaluate the long-term immuno-metabolic consequences of burn injury combining metabolite, lipoprotein, and cytokine panels. Plasma samples from 36 children aged 4-8 years were collected 3 years after a burn injury together with 21 samples from non-injured age and sex matched controls. Three different 1H Nuclear Magnetic Resonance spectroscopic experiments were applied to capture information on plasma low molecular weight metabolites, lipoproteins, and α-1-acid glycoprotein.
Results:
Burn injury was characterized by underlying signatures of hyperglycaemia, hypermetabolism and inflammation, suggesting disruption of multiple pathways relating to glycolysis, tricarboxylic acid cycle, amino acid metabolism and the urea cycle. In addition, very low-density lipoprotein sub-components were significantly reduced in participants with burn injury whereas small-dense low density lipoprotein particles were significantly elevated in the burn injured patient plasma compared to uninjured controls, potentially indicative of modified cardiometabolic risk after a burn. Weighted-node Metabolite Correlation Network Analysis was restricted to the significantly differential features (q <0.05) between the children with and without burn injury and demonstrated a striking disparity in the number of statistical correlations between cytokines, lipoproteins, and small molecular metabolites in the injured groups, with increased correlations between these groups.
Discussion:
These findings suggest a 'metabolic memory' of burn defined by a signature of interlinked and perturbed immune and metabolic function. Burn injury is associated with a series of adverse metabolic changes that persist chronically and are independent of burn severity and this study demonstrates increased risk of cardiovascular disease in the long-term. These findings highlight a crucial need for improved longer term monitoring of cardiometabolic health in a vulnerable population of children that have undergone burn injury.
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