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

Diabetes Obes Metab. 2014 Dec;16(12):1269-73. doi: 10.1111/dom.12357. Epub 2014 Aug 13.

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.

Keywords: diabetes mellitus; drug mechanism; experimental pharmacology; type 2 diabetes; β cell.

Publication types

  • Letter
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / drug therapy*
  • 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 Protein / administration & dosage
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Middle Aged
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Interleukin-1