TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome - PubMed (original) (raw)

Randomized Controlled Trial

. 2011 Jan;96(1):E146-50.

doi: 10.1210/jc.2010-1170. Epub 2010 Nov 3.

Affiliations

Randomized Controlled Trial

TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome

Takara L Stanley et al. J Clin Endocrinol Metab. 2011 Jan.

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Effect of etanercept on glucose, hsCRP, and adiponectin: changes in etanercept (black bars) and placebo (white bars) groups. Error bars are

se

. A, Percent change in fasting glucose at 3 and 6 months; P = 0.02 for etanercept vs. placebo by repeated-measures ANCOVA. B, Change in log10 hsCRP at 3 and 6 months. *, P = 0.03 for change in etanercept vs. placebo at 3 months controlling for age and race. Change between groups is not significantly different at 6 months. C, Aggregate percent change in total adiponectin, HMW adiponectin, and ratio of HMW to total adiponectin over 6 months. *, P < 0.05 for etanercept vs. placebo by repeated-measures ANCOVA.

Similar articles

Cited by

References

    1. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G 2001 Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751 - PubMed
    1. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM 1995 Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415 - PMC - PubMed
    1. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T 1998 Tumor necrosis factor-α in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83:2907–2910 - PubMed
    1. Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R 1996 Effects of an engineered human anti-TNF-α antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45:881–885 - PubMed
    1. Paquot N, Castillo MJ, Lefèbvre PJ, Scheen AJ 2000 No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 85:1316–1319 - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources