PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study

Mirjafari, Hoda; Ruperto, N; Brunner, HI; Żuber, Zbigniew; Zulian, Francesco; Maldonado-Velázquez,; Mantzourani, Evangelia; Murray, Katherine; Roth, J.; Rovenský, J; Vougiouka, Olga; Wang, J; Harari, Olivier; Lovell, Daniel J.; Martini, A.; Benedetti, Fabrizio

doi:10.1186/1546-0096-11-s2-o23

Cited by 4 publications

(4 citation statements)

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“…Indeed, we found 6 articles investigating the effect of tocilizumab on insulin resistance. Of these, the majority of studies [41,[43][44][45]] demonstrated a beneficial effect, while the remaining two [46,47] failed to demonstrate any recognizable modification of insulin resistance following tocilizumab administration. Of note, amongst the studies demonstrating a positive effect there was a wellpowered subanalysis of a major clinical trial [43].…”

Section: Discussionmentioning

confidence: 99%

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The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Ursini

Russo

Ruscitti

et al. 2018

Autoimmunity Reviews

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Section: Discussionmentioning

confidence: 99%

“…A similar approach was used in a subanalysis of the TENDER clinical trial [44] in which 40 patients with systemic juvenile idiopathic arthritis (SJIA) were evaluated before and after 6 weeks of treatment with i.v. tocilizumab at appropriate dose for weight range.…”

Section: Tocilizumabmentioning

confidence: 99%

The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Ursini

Russo

Ruscitti

et al. 2018

Autoimmunity Reviews

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“…Furthermore, C-reactive protein has been found to be positively correlated with abdominal adipose tissue accumulation in men (174). Notably, IL-6 (245), IL-1␤ (130), and TNF-␣ can directly inhibit insulin signaling, and targeting these cytokines by neutralizing antibodies has shown some beneficial anti-diabetic effects in clinical studies (49,159,205,215).…”

Section: A Chronic Inflammation Links Hypertrophic Obesity To Insulimentioning

confidence: 99%

Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity

Hammarstedt

Gogg

Hedjazifar

et al. 2018

Physiological Reviews

331

256

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The subcutaneous adipose tissue (SAT) is the largest and best storage site for excess lipids. However, it has a limited ability to expand by recruiting and/or differentiating available precursor cells. When inadequate, this leads to a hypertrophic expansion of the cells with increased inflammation, insulin resistance, and a dysfunctional prolipolytic tissue. Epi-/genetic factors regulate SAT adipogenesis and genetic predisposition for type 2 diabetes is associated with markers of an impaired SAT adipogenesis and development of hypertrophic obesity also in nonobese individuals. We here review mechanisms for the adipose precursor cells to enter adipogenesis, emphasizing the role of bone morphogenetic protein-4 (BMP-4) and its endogenous antagonist gremlin-1, which is increased in hypertrophic SAT in humans. Gremlin-1 is a secreted and a likely important mechanism for the impaired SAT adipogenesis in hypertrophic obesity. Transiently increasing BMP-4 enhances adipogenic commitment of the precursor cells while maintained BMP-4 signaling during differentiation induces a beige/brown oxidative phenotype in both human and murine adipose cells. Adipose tissue growth and development also requires increased angiogenesis, and BMP-4, as a proangiogenic molecule, may also be an important feedback regulator of this. Hypertrophic obesity is also associated with increased lipolysis. Reduced lipid storage and increased release of FFA by hypertrophic SAT are important mechanisms for the accumulation of ectopic fat in the liver and other places promoting insulin resistance. Taken together, the limited expansion and storage capacity of SAT is a major driver of the obesity-associated metabolic complications.

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“…The proposed mechanism for improving insulin sensitivity by this biologic agent is the reduction of adipose tissue inflammation by lessening effector T-cell infiltration and polarizing macrophages to the anti-inflammatory M2 phenotype[ 119 , 127 ]. In two studies with limited patient numbers[ 65 , 118 ], one failed to demonstrate the effects on IR reduction after ABA therapy for 12 wk, while another showed improved insulin sensitivity under a 6 mo treatment period. In addition, improved leptin/adiponectin ratios, an alternative marker of IR, was identified in RA patients treated with non-TNF-α targeted agents including ABA and TCZ as compared with those receiving TNFi therapy[ 124 ].…”

Section: Role Of Il-6 In Irmentioning

confidence: 99%

Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Wang¹,

Tsai²

2021

WJD

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In addition to β-cell failure with inadequate insulin secretion, the crucial mechanism leading to establishment of diabetes mellitus (DM) is the resistance of target cells to insulin, i.e . insulin resistance (IR), indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor, downstream to the substrates of insulin action. IR is a common feature of most metabolic disorders, particularly type II DM as well as some cases of type I DM. A variety of human inﬂammatory disorders with increased levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, have been reported to be associated with an increased risk of IR. Autoimmune-mediated arthritis conditions, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with the involvement of proinflammatory cytokines as their central pathogenesis, have been demonstrated to be associated with IR, especially during the active disease state. There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders. In this review, we focus on the effects of anti-TNF-α- and non-TNF-α-targeted therapies on IR in patients with RA, PsA and AS. Anti-TNF-α therapy, IL-1 blockade, IL-6 antagonist, Janus kinase inhibitor and phospho-diesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

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PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study

Cited by 4 publications

References 0 publications

The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity

Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

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