The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2014-12, Vol.16 (12), p.1269-1273
• Main Authors: van Poppel, P. C. M., van Asseldonk, E. J. P., Holst, J. J., Vilsbøll, T., Netea, M. G., Tack, C. J.
• Format: Article
• Language: English
• Subjects: Beta cells; Blood Glucose - drug effects; Cross-Over Studies; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; drug mechanism; experimental pharmacology; Female; Glucose Intolerance - blood; Glucose Intolerance - drug therapy; Glucose tolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein - administration & dosage; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Male; Middle Aged; Placebos; Receptors, Interleukin-1 - antagonists & inhibitors; Treatment Outcome; type 2 diabetes; β cell
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12357

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.