title: The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance.
abstract: Inflammation at the level of the β cell appears to be involved in progressive β-cell dysfunction in type 2 diabetes. We assessed the effect of blocking interleukin-1 (IL-1) by anakinra [recombinant human interleukin-1 receptor antagonist (IL-1Ra)] on β-cell function. Sixteen participants with impaired glucose tolerance were treated with 150 mg anakinra daily for 4 weeks in a double blind, randomized, placebo-controlled cross-over study with a wash-out period of 4 weeks. At the end of each treatment period, oral glucose tolerance tests (OGTTs) and hyperglycaemic clamps were performed. First-phase insulin secretion improved after anakinra treatment compared with placebo, 148 ± 20 versus 123 ± 14 mU/l, respectively (p = 0.03), and the insulinogenic index was higher after anakinra treatment. These results support the concept of involvement of IL-1β in the (progressive) decrease of insulin secretion capacity associated with type 2 diabetes.
authors.affiliation: Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: P C M
authors.initials: PC
authors.lastname: van Poppel
authors.forename: E J P
authors.initials: EJ
authors.lastname: van Asseldonk
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: C J
authors.initials: CJ
authors.lastname: Tack
mesh_terms: D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1
keywords: diabetes mellitus; drug mechanism; experimental pharmacology; type 2 diabetes; β cell