Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes.
OBJECTIVE
Interleukin (IL)-1 impairs insulin secretion and induces beta-cell apoptosis. Pancreatic beta-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 beta-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses.


METHODS
Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m(2) 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 beta-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.
Larsen
Claus M
CM
Hagedorn Research Institute and Steno Diabetes Center, Gentofte, Denmark.
Faulenbach
Mirjam
M
Vaag
Allan
A
Ehses
Jan A
JA
Donath
Marc Y
MY
Mandrup-Poulsen
Thomas
T
D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D055815:Young Adult
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein