title: Interleukin-1 antagonists for diabetes.
abstract: BACKGROUND
  Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity and mortality from late micro- and macrovascular complications, and despite current best clinical practice diabetes is still associated with shortened lifespan. There is an unmet need for interventions targeting pathogenetic mechanisms in diabetes, and the market for such therapies is huge.
  
  
  METHODS
  Diabetes occurs when insulin secretion fails to meet tissue needs as a consequence of reduced functional beta-cell mass or reduced insulin sensitivity. Chronic inflammation contributes to beta-cell failure and insulin resistance. Molecular details are accumulating on the underlying cellular and molecular pathways. The testing of specific anti-inflammatory biologics targeting single pro-inflammatory cytokines has provided clinical proof-of-concept.
  
  
  CONCLUSIONS
  IL-1 antagonists have so far failed to meet primary end points in recent-onset type 1 diabetes in Phase IIa, and promising Phase I and IIa trials in type 2 diabetes need confirmation in Phase III. The magnitude of response is variable and may relate to sub-phenotypes of these heterogeneous disorders. More studies are required to appreciate the potential of these drugs in diabetes.
authors.affiliation: University of Copenhagen, Panum Institute (12.2.10), Faculty of Health and Medical Sciences, Department of Biomedical Sciences, Section for Endocrinological Research, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. tmpo@sund.ku.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007375:Interleukin-1