TNF-α Antagonism with Etanercept Decreases Glucose and Increases the Proportion of High Molecular Weight Adiponectin in Obese Subjects with Features of the Metabolic Syndrome
Year: 2010
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: CONTEXT AND OBJECTIVE: Obesity is associated with activation of the TNF-α system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-α with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known. DESIGN AND PARTICIPANTS: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months. OUTCOME MEASURES: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-α mRNA expression. RESULTS: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-α and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, -10.8 ± 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 ± 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (-11 ± 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months. CONCLUSIONS: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation.
DOI: 10.1210/jc.2010-1170
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Augmenting Pulsatile Growth Hormone: Metabolic Effects in HIV-Infection, Effects of TNF-a Antagonism in Patients with Obesity and Metabolic Dysregulation, Growth Hormone Releasing Hormone in Patients with HIV Lipodystrophy, Harvard Clinical and Translational Science Center (UL1), General Clinical Research Center, Growth Hormone, Mitochondria, and Cardio-metabolic Complications of Obesity, Integrative Metabolic Adaptations to Enviromental and Nutritional Challenge, Strategies to Improve CAD Risk In HIV Disease, Boston Area Nutrition Obesity Research Center (NORC)
OpenAlex ID: W2125058279