期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 96, 期 1, 页码 E146-E150出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2010-1170
关键词
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资金
- Amgen
- National Institutes of Health (NIH) [M01-RR-01066, 1 UL1 RR025758-01]
- Harvard Clinical and Translational Science Center, National Center for Research Resources
- NIH [F32 DK080642-02, K23 DK089910-01, K24 DK064545-06, PO1-DK049210, F32 DK085969-01]
- Danish Agency for Science, Technology, and Innovation
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025758, M01RR001066] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K23DK087857, P30DK040561, K23DK089910, F32DK080642, K24DK064545, F32DK085969, P01DK049210] Funding Source: NIH RePORTER
Context and Objective: Obesity is associated with activation of the TNF-alpha 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-alpha 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-alpha 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-alpha 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. (J Clin Endocrinol Metab 96: E146-E150, 2011)
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