Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

Helena Dominguez; Heidi Storgaard; Christian Rask-Madsen; Thomas Steffen Hermann; Nikolaj Ihlemann; Dorthe Baunbjerg Nielsen; Camilla Spohr; Lars Valeur Køber; Allan Vaag; Christian Torp-Pedersen

doi:10.1159/000088261

Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

Helena Dominguez, Heidi Storgaard, Christian Rask-Madsen, Thomas Steffen Hermann, Nikolaj Ihlemann, Dorthe Baunbjerg Nielsen, Camilla Spohr, Lars Valeur Køber, Allan Vaag, Christian Torp-Pedersen

Department of Clinical Medicine

215 Citations (Scopus)

Abstract

OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha 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. Beta-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. Beta-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.

Original language	English
Journal	Journal of Vascular Research
Volume	42
Issue number	6
Pages (from-to)	517-25
Number of pages	8
ISSN	1018-1172
DOIs	https://doi.org/10.1159/000088261
Publication status	Published - 2005

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Dominguez, H., Storgaard, H., Rask-Madsen, C., Steffen Hermann, T., Ihlemann, N., Baunbjerg Nielsen, D., Spohr, C., Køber, L. V., Vaag, A., & Torp-Pedersen, C. (2005). Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. Journal of Vascular Research, 42(6), 517-25. https://doi.org/10.1159/000088261

Dominguez, H, Storgaard, H, Rask-Madsen, C, Steffen Hermann, T, Ihlemann, N, Baunbjerg Nielsen, D, Spohr, C, Køber, LV , Vaag, A & Torp-Pedersen, C 2005, 'Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes', Journal of Vascular Research, vol. 42, no. 6, pp. 517-25. https://doi.org/10.1159/000088261

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title = "Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes",

abstract = "OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha 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. Beta-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. Beta-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.",

author = "Helena Dominguez and Heidi Storgaard and Christian Rask-Madsen and {Steffen Hermann}, Thomas and Nikolaj Ihlemann and {Baunbjerg Nielsen}, Dorthe and Camilla Spohr and K{\o}ber, {Lars Valeur} and Allan Vaag and Christian Torp-Pedersen",

note = "Keywords: Adult; Biological Markers; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Immunoglobulin G; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Vasodilation",

year = "2005",

doi = "10.1159/000088261",

language = "English",

volume = "42",

pages = "517--25",

journal = "Journal of Vascular Research",

issn = "1018-1172",

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TY - JOUR

T1 - Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

AU - Dominguez, Helena

AU - Storgaard, Heidi

AU - Rask-Madsen, Christian

AU - Steffen Hermann, Thomas

AU - Ihlemann, Nikolaj

AU - Baunbjerg Nielsen, Dorthe

AU - Spohr, Camilla

AU - Køber, Lars Valeur

AU - Vaag, Allan

AU - Torp-Pedersen, Christian

N1 - Keywords: Adult; Biological Markers; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Immunoglobulin G; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Vasodilation

PY - 2005

Y1 - 2005

N2 - OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha 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. Beta-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. Beta-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.

AB - OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha 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. Beta-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. Beta-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.

U2 - 10.1159/000088261

DO - 10.1159/000088261

M3 - Journal article

C2 - 16155368

SN - 1018-1172

VL - 42

SP - 517

EP - 525

JO - Journal of Vascular Research

JF - Journal of Vascular Research

IS - 6

ER -

Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

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