PT  - JOURNAL ARTICLE
AU  - Larsen, Claus M.
AU  - Faulenbach, Mirjam
AU  - Vaag, Allan
AU  - Ehses, Jan A.
AU  - Donath, Marc Y.
AU  - Mandrup-Poulsen, Thomas
TI  - Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes
AID  - 10.2337/dc09-0533
DP  - 2009 Sep 01
TA  - Diabetes Care
PG  - 1663--1668
VI  - 32
IP  - 9
4099  - http://care.diabetesjournals.org/content/32/9/1663.short
4100  - http://care.diabetesjournals.org/content/32/9/1663.full
SO  - Diabetes Care2009 Sep 01; 32
AB  - OBJECTIVE Interleukin (IL)-1 impairs insulin secretion and induces β-cell apoptosis. Pancreatic β-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 β-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 β-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.