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Updated: Jun 4, 2026
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Proteomics and metabolomics reveal growth hormone deficiency-induced complement and metabolic dysregulation in
Guirong Bai1,2, Xiaomin Xie3,4, Shiting Li2
1Department of Endocrinology, The First People's Hospital of Yinchuan, Yinchuan, Ningxia, China.
Insights
Growth hormone (GH) deficiency in Post-COVID-19 condition (PCC) is linked to immune system changes. SPARCL1 protein may serve as a biomarker for GH deficiency in PCC patients.
Area of Science:
- Endocrinology
- Immunology
- Systems Biology
Background:
- Post-COVID-19 condition (PCC) frequently involves endocrine and immune system dysregulation.
- Growth hormone (GH) deficiency has been observed in PCC patients, but its systemic impact requires further elucidation.
Purpose of the Study:
- To investigate the systemic effects of GH deficiency in PCC patients.
- To identify potential biomarkers for GH deficiency in the context of PCC.
Main Methods:
- Eighty-eight PCC patients were categorized into four groups based on GH levels.
- Insulin tolerance testing (ITT) was used to assess GH and cortisol levels.
- Proteomic and metabolomic analyses were performed on serum samples, followed by correlation analyses with GH and cortisol levels.
Main Results:
- Significant differences in GH and cortisol levels were observed across the four groups post-ITT.
- Proteomic analysis revealed alterations in complement and coagulation cascades, with reduced lipid transport proteins in GH-deficient patients.
- Metabolomic profiling identified L-glutamic acid and traumatic acid as potential discriminators of GH deficiency, and tetradecanedioic acid correlated positively with GH levels.
Conclusions:
- GH deficiency in PCC patients is associated with complement dysregulation.
- SPARCL1 protein is highlighted as a potential biomarker for GH deficiency in PCC patients.
- Integrated proteomic and metabolomic analyses reveal significant associations between protein and metabolite changes and GH levels.
Introduction:
Post-COVID-19 condition (PCC) is often accompanied by endocrine and immune dysregulation. Growth hormone (GH)deficiency has been reported in PCC patients, but its systemic effects remain poorly defined.
Material And Methods:
Eighty-eight PCC patients were classified into four groups based on GH levels (A: GH ≥ 10 ng/mL; B:5 ng/mL ≤ GH < 10 ng/mL; C: 1 ng/mL ≤ GH < 5 ng/mL; D: GH < 1 ng/mL), and insulin tolerance testing was performed to assess GH and cortisol levels. Serum samples from PCC patients were analyzed using proteomics and metabolomics, followed by correlation analyseswith GH and cortisol levels.
Results:
There were significant differences among the four groups in GH levels at baseline, 30, 60, 90, and 120 minutes after ITT. Similarly, cortisol levels at 30, 60, 90, and 120 minutes post ITT also showed significant differences among the four groups. Proteomic profiling identifiedsignificant alterations of proteins in complement and coagulation cascades across different GH levels. Compared with group B, groupD (GH deficiency) showed reduced expression of lipid transport proteins (such as APOB, APOH, and APOF), consistent with the lowerserum low-density lipoprotein cholesterol (LDL-C) levels observed in the GH deficiency group. Integrative analysis of comparisons amonggroups highlighted SPARCL1 as a hub protein linked to GH dysregulation, showing a critical response to declining GH. Correlation analysisalso revealed strong associations of F/GH levels with complement-related proteins and SPARCL1. Metabolomic profiling revealed that L-glutamic acid and traumatic acid were significantly elevated in group C compared with group B, with AUC values of 0.657 and 0.739,respectively, indicating that these metabolites can distinguish patients with normal GH from those with GH deficiency. In addition, tetradecanedioicacid, which was markedly increased in group C compared to group D, showed a significant positive correlation with GHlevels at multiple time points. Integrated proteomic and metabolomic analyses further demonstrated significant associations betweendifferentially abundant proteins and metabolites.
Conclusions:
Our integrated proteomic-metabolomic analysis reveals that GH deficiency in PCC patients is associated with complement dysregulation, highlighting SPARCL1 as a potential biomarker of GH deficiency in PCC patients.
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