Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes
| Autor: | Dorthe Baunbjerg Nielsen, Allan Vaag, Nikolaj Ihlemann, Christian Torp-Pedersen, Christian Rask-Madsen, Helena Dominguez, Camilla Spohr, Heidi Storgaard, Lars Køber, Thomas Steffen Hermann |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Endothelium Physiology medicine.medical_treatment Type 2 diabetes Receptors Tumor Necrosis Factor Etanercept Insulin resistance Internal medicine Diabetes mellitus Insulin-Secreting Cells medicine Humans Obesity Inflammation business.industry Interleukin-6 Tumor Necrosis Factor-alpha Insulin Glucose Tolerance Test Middle Aged medicine.disease Vasodilation Cytokine Endocrinology medicine.anatomical_structure C-Reactive Protein Diabetes Mellitus Type 2 Immunoglobulin G Tumor necrosis factor alpha Female Insulin Resistance Cardiology and Cardiovascular Medicine business Biomarkers medicine.drug |
| Zdroj: | Journal of vascular research. 42(6) |
| ISSN: | 1018-1172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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