Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome
Abstract Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate eff...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-87207-w |
| _version_ | 1818857675438424064 |
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| author | Fahim Ebrahimi Sandrine Andrea Urwyler Matthias Johannes Betz Emanuel Remigius Christ Philipp Schuetz Beat Mueller Marc Yves Donath Mirjam Christ-Crain |
| author_facet | Fahim Ebrahimi Sandrine Andrea Urwyler Matthias Johannes Betz Emanuel Remigius Christ Philipp Schuetz Beat Mueller Marc Yves Donath Mirjam Christ-Crain |
| author_sort | Fahim Ebrahimi |
| collection | DOAJ |
| description | Abstract Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44–66), 26% were female and median BMI was 37 kg/m2 (IQR 34–39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by − 200 pg/mL (95%CI − 334 to − 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: − 8.8 pg/mL (95%CI − 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI − 236 to − 113; p < 0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome. Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276. |
| first_indexed | 2024-12-19T08:44:10Z |
| format | Article |
| id | doaj.art-75c030291fae4f3cb1dc576983dc4f52 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:44:10Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-75c030291fae4f3cb1dc576983dc4f522022-12-21T20:28:51ZengNature PortfolioScientific Reports2045-23222021-04-011111810.1038/s41598-021-87207-wEffects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndromeFahim Ebrahimi0Sandrine Andrea Urwyler1Matthias Johannes Betz2Emanuel Remigius Christ3Philipp Schuetz4Beat Mueller5Marc Yves Donath6Mirjam Christ-Crain7Division of Endocrinology, Diabetes, and Metabolism, University Hospital BaselDivision of Endocrinology, Diabetes, and Metabolism, University Hospital BaselDivision of Endocrinology, Diabetes, and Metabolism, University Hospital BaselDivision of Endocrinology, Diabetes, and Metabolism, University Hospital BaselDepartment of Clinical Research, University Hospital BaselDepartment of Clinical Research, University Hospital BaselDivision of Endocrinology, Diabetes, and Metabolism, University Hospital BaselDivision of Endocrinology, Diabetes, and Metabolism, University Hospital BaselAbstract Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44–66), 26% were female and median BMI was 37 kg/m2 (IQR 34–39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by − 200 pg/mL (95%CI − 334 to − 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: − 8.8 pg/mL (95%CI − 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI − 236 to − 113; p < 0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome. Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.https://doi.org/10.1038/s41598-021-87207-w |
| spellingShingle | Fahim Ebrahimi Sandrine Andrea Urwyler Matthias Johannes Betz Emanuel Remigius Christ Philipp Schuetz Beat Mueller Marc Yves Donath Mirjam Christ-Crain Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome Scientific Reports |
| title | Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome |
| title_full | Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome |
| title_fullStr | Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome |
| title_full_unstemmed | Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome |
| title_short | Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome |
| title_sort | effects of interleukin 1 antagonism and corticosteroids on fibroblast growth factor 21 in patients with metabolic syndrome |
| url | https://doi.org/10.1038/s41598-021-87207-w |
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