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IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes: An observational study.

Abstract
Recently, it has been shown that some well-known pathogenic mediators in rheumatoid arthritis (RA), such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), could play a pathogenic role in insulin resistance and (IR) and type 2 diabetes (T2D).In this 6-month longitudinal study, we aimed at investigating if the inhibition of IL-1 or TNF is associated with an improvement of IR in RA patients with comorbid T2D and the possible effects on selected serum adipokines. RA patients with comorbid T2D were recruited among those undergoing treatment with anakinra (ANA) or with TNF inhibitor (TNFi). The 1998-updated version of the Homeostasis Model Assessment (HOMA2) was used to calculate surrogate indexes of IR (HOMA2-IR) and steady-state beta cell function (%B) from fasting values of glucose and C-peptide. Glucagon, adiponectin, adipsin, leptin, and resistin were also measured. All these parameters were collected at baseline, after 3 and 6 months of treatment.ANA-treated patients showed a significant improvement in HOMA2-%β, HOMA2-IR, and glucagon. In TNFi-treated patients, no significant difference was observed analyzing these metabolic parameters. Adipsin and resistin decreased after 6 months in ANA-treated patients whereas, no difference was recognized analyzing adiponectin and leptin. In TNFi-treated patients, leptin and resistin significantly increased, whereas no difference was found analyzing adiponectin and adipsin, during the follow-up.Our data may suggest a beneficial effect of IL-1 inhibition on measures of metabolic derangement in RA-associated T2D. If further confirmed by larger studies, IL-1 targeting therapies may represent a tailored approach in these patients.
AuthorsPiero Ruscitti, Francesco Ursini, Paola Cipriani, Marta Greco, Saverio Alvaro, Liakouli Vasiliki, Paola Di Benedetto, Francesco Carubbi, Onorina Berardicurti, Elio Gulletta, Giovambattista De Sarro, Roberto Giacomelli
JournalMedicine (Medicine (Baltimore)) Vol. 98 Issue 7 Pg. e14587 (Feb 2019) ISSN: 1536-5964 [Electronic] United States
PMID30762811 (Publication Type: Journal Article, Observational Study)
Chemical References
  • Adipokines
  • Blood Glucose
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
Topics
  • Adipokines (metabolism)
  • Aged
  • Arthritis, Rheumatoid (epidemiology, physiopathology)
  • Blood Glucose (drug effects)
  • Body Mass Index
  • Diabetes Mellitus, Type 2 (epidemiology, physiopathology)
  • Female
  • Humans
  • Insulin Resistance (physiology)
  • Interleukin 1 Receptor Antagonist Protein (pharmacology)
  • Interleukin-1 (antagonists & inhibitors)
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha (antagonists & inhibitors)

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