Metabolic and Vascular Effects of Tumor Necrosis Factor-α Blockade with Etanercept in Obese Patients with Type 2 Diabetes
Abstract
Objective: The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-α blockade with etanercept could reverse vascular and metabolic insulin resistance. Method and Results: Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions of serotonin, sodium nitroprusside and insulin co-infused with serotonin. β-Cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly with etanercept (C-reactive protein from 9.9 ± 3.1 to 4.8 ± 1.4 mg l–1, p = 0.04; interleukin-6 from 3.1 ± 0.4 to 1.9 ± 0.2 ng l–1, p = 0.03). Vasodilatory responses to serotonin and sodium nitroprusside infusions remained unchanged. Insulin effect on vasodilatation and on whole-body and forearm glucose uptake remained unchanged as well. β-Cell function tended to improve. Conclusion: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed.
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These genes belonged to at least twelve functional families including cytokines, complement cascade, acute-phase proteins, adhesion and extracellular matrix remodelling.
“These genes belonged to at least twelve functional families including cytokines, the complement factor cascade, acute-phase proteins of inflammation, and molecules involved in cellular adhesion and in the remodelling of the extracellular matrix.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [127]
The improved inflammatory profile involved decreased pro-inflammatory and increased anti-inflammatory gene expression, such as IL-10 and IL-1ra.
“The improvement of the inflammatory profile (at the level of gene expression) involved both the decreased expression of pro-inflammatory factors and the increased expression of anti-inflammatory factors such as IL-10 and IL-1ra.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [127]
A hypoenergetic diet in obese women significantly modified expression of inflammatory genes in subcutaneous adipose tissue.
“There was a significant modification in the expression of inflammatory genes in the subcutaneous adipose tissue of obese women following a hypoenergetic diet (127) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [127]
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- Authors
- Dominguez, H., Storgaard, H., Rask-Madsen, C., Steffen Hermann, T., Ihlemann, N., Baunbjerg Nielsen, D., Spohr, C., Kober, L., Vaag, A., & Torp-Pedersen, C.
- Affiliations
- Bispebjerg Hospital (DK)
- Venue
- Journal of Vascular Research
- Publisher
- S. Karger AG
- Published
- 2005
- Volume
- 42
- Issue
- 6
- Pages
- 517-525
- ISSN
- 1018-1172 (ISSN-L)
- 1423-0135
- OpenAlex
- W2010447832
- Cited by
- 286
- References
- 49
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 19 · 2022: 16 · 2021: 14 · 2020: 8 · 2019: 14 · 2018: 15 · 2017: 16 · 2016: 15 · 2015: 17 · 2014: 18 · 2013: 21 · 2012: 14
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Vascular Research (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- etanercept, type 2 diabetes, obesity, insulin resistance, endothelial dysfunction, insulin sensitivity, beta-cell function, C-reactive protein, interleukin-6, inflammation, forearm blood flow, glucose uptake, vasodilation
- MeSH terms
- Etanercept, Interleukin-6 Inhibitors, Adult, C-Reactive Protein, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Immunoglobulin G, Inflammation, Insulin Resistance, Male, Middle Aged, Obesity, Tumor Necrosis Factor-alpha, Vasodilation, Biomarkers, Interleukin-6, Receptors, Tumor Necrosis Factor, Insulin-Secreting Cells
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