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ArtikelSustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes  
Oleh: Larsen, Claus M. ; Faulenbach, Mirjam ; Vaag, Allan ; Ehses, Jan A.
Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 32 no. 09 (Sep. 2009), page 1663-1668.
Topik: DIABETES; DIABETES MELLITUS; Interleukin-1 Receptor Antagonist Treatment; Type 2 Diabetes
  • Perpustakaan FK
    • Nomor Panggil: D05.K.2009.03
    • Non-tandon: 1 (dapat dipinjam: 0)
    • Tandon: tidak ada
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Isi artikelOBJECTIVE : Interleukin (IL)-1 impairs insulin secretion and induces ß-cell apoptosis. Pancreatic ß-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and ß-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS : Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m2 and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in ß-cell function after anakinra withdrawal. Analysis was done by intention to treat. RESULTS : Thirty-nine weeks after anakinra withdrawal, the proinsulin-to-insulin (PI/I) ratio but not stimulated C-peptide remained improved (by -0.07 [95% CI -0.14 to -0.02], P = 0.011) compared with values in placebo-treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions in C-reactive protein (-3.2 mg/l [-6.2 to -1.1], P = 0.014) and in IL-6 (-1.4 ng/l [-2.6 to -0.3], P = 0.036) were maintained until the end of study. CONCLUSIONS : IL-1 blockade with anakinra induces improvement of the PI/I ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal.
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