Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis
Abstract Background In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case–control study utilized plasma proteomics to exp...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-024-01056-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850118834131828736 |
|---|---|
| author | Paolo Spagnolo Enis Cela Maitray A. Patel David Tweddell Mark Daley Cheril Clarson Saverio Stranges Gediminas Cepinskas Douglas D. Fraser |
| author_facet | Paolo Spagnolo Enis Cela Maitray A. Patel David Tweddell Mark Daley Cheril Clarson Saverio Stranges Gediminas Cepinskas Douglas D. Fraser |
| author_sort | Paolo Spagnolo |
| collection | DOAJ |
| description | Abstract Background In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case–control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables. Methods We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes. Proximity extension assays were used to quantify 3072 plasma proteins. Data analysis was performed using multivariate statistics, machine learning, and bioinformatics. Results This study identified 214 differentially expressed proteins (162 upregulated, 52 downregulated; adj P < 0.05 and a fold change > 2), reflecting cellular dysfunction and metabolic stress in severe DKA. We characterized protein expression across various organ systems and cell types, with notable alterations observed in white blood cells. Elevated inflammatory pathways suggest an enhanced inflammatory response, which may contribute to the complications of severe DKA. Additionally, upregulated pathways related to hormone signaling and nitrogen metabolism were identified, consistent with increased hormone release and associated metabolic processes, such as glycogenolysis and lipolysis. Changes in lipid and fatty acid metabolism were also observed, aligning with the lipolysis and ketosis characteristic of severe DKA. Finally, several signaling pathways were associated with clinical biochemical variables. Conclusions Our findings highlight differentially expressed plasma proteins and enriched signaling pathways that were associated with clinical features, offering insights into the pathophysiology of severe DKA. |
| format | Article |
| id | doaj-art-4095c847039c48dc9e133118acbf3d8d |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-4095c847039c48dc9e133118acbf3d8d2025-08-20T02:35:47ZengBMCMolecular Medicine1528-36582025-01-0131111410.1186/s10020-024-01056-7Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosisPaolo Spagnolo0Enis Cela1Maitray A. Patel2David Tweddell3Mark Daley4Cheril Clarson5Saverio Stranges6Gediminas Cepinskas7Douglas D. Fraser8Medicine, Campus Bio-Medico University of RomePhysiology and Pharmacology, Western UniversityEpidemiology and Biostatistics, Western UniversityComputer Science, Western UniversityEpidemiology and Biostatistics, Western UniversityPediatrics, Western UniversityEpidemiology and Biostatistics, Western UniversityMedical Biophysics, Western UniversityPhysiology and Pharmacology, Western UniversityAbstract Background In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case–control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables. Methods We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes. Proximity extension assays were used to quantify 3072 plasma proteins. Data analysis was performed using multivariate statistics, machine learning, and bioinformatics. Results This study identified 214 differentially expressed proteins (162 upregulated, 52 downregulated; adj P < 0.05 and a fold change > 2), reflecting cellular dysfunction and metabolic stress in severe DKA. We characterized protein expression across various organ systems and cell types, with notable alterations observed in white blood cells. Elevated inflammatory pathways suggest an enhanced inflammatory response, which may contribute to the complications of severe DKA. Additionally, upregulated pathways related to hormone signaling and nitrogen metabolism were identified, consistent with increased hormone release and associated metabolic processes, such as glycogenolysis and lipolysis. Changes in lipid and fatty acid metabolism were also observed, aligning with the lipolysis and ketosis characteristic of severe DKA. Finally, several signaling pathways were associated with clinical biochemical variables. Conclusions Our findings highlight differentially expressed plasma proteins and enriched signaling pathways that were associated with clinical features, offering insights into the pathophysiology of severe DKA.https://doi.org/10.1186/s10020-024-01056-7PediatricDiabetic ketoacidosisProteomicsProtein expressionPathways |
| spellingShingle | Paolo Spagnolo Enis Cela Maitray A. Patel David Tweddell Mark Daley Cheril Clarson Saverio Stranges Gediminas Cepinskas Douglas D. Fraser Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis Molecular Medicine Pediatric Diabetic ketoacidosis Proteomics Protein expression Pathways |
| title | Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| title_full | Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| title_fullStr | Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| title_full_unstemmed | Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| title_short | Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| title_sort | differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis |
| topic | Pediatric Diabetic ketoacidosis Proteomics Protein expression Pathways |
| url | https://doi.org/10.1186/s10020-024-01056-7 |
| work_keys_str_mv | AT paolospagnolo differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT eniscela differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT maitrayapatel differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT davidtweddell differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT markdaley differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT cherilclarson differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT saveriostranges differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT gediminascepinskas differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis AT douglasdfraser differentialexpressionofplasmaproteinsandpathwayenrichmentsinpediatricdiabeticketoacidosis |