IL-1 and Type 2 Diabetes

Inflammation and Interleukin-1: A New Approach to Type 2 Diabetes

Type 2 diabetes is commonly regarded as a disorder involving chronically elevated blood sugar levels and the administration of insulin to help overcome this imbalance.  But a ground-breaking proof-of-concept study published in The New England Journal of Medicine[1] has provided a new understanding of Type 2 diabetes as a disease caused by inflammation.

In the study, blockade of the master pro-inflammatory signaling protein, Interleukin-1 (IL-1), resulted in disease improvement for Type 2 diabetes patients. IL-1 is produced by the body in response to inflammatory stimuli and mediates inflammatory responses.  Elevated levels of IL-1 have been shown to damage and destroy insulin-producing cells.  

The findings suggest that the class of IL-1 blockers, such as XOMA 052, have the potential to modify Type 2 diabetes by preserving insulin-producing cells, not just control disease symptoms. Whereas most Type 2 diabetes medicines focus on maximizing insulin production by the pancreas or increasing the body’s sensitivity to insulin, IL-1 blockers target the inflammatory response that can devastate insulin-producing cells.

In the published study, patients with Type 2 diabetes were given the drug anakinra.  Although anakinra was developed and approved for the treatment of rheumatoid arthritis, the researchers chose to investigate the drug’s ability to treat Type 2 diabetes because of its proven ability to block IL-1 and its excellent safety profile.

Patients who received anakinra demonstrated improvements in diabetes-specific measures such as glycated hemoglobin (HbA1c) levels, insulin production, blood sugar control, and pancreatic beta cell function.  They also demonstrated decreases in systemic inflammation as measured by C-reactive protein levels and other tests.

A second follow-up study of the patients in the original New England Journal of Medicine study demonstrated that, nine months after final treatment with anakinra, insulin usage was reduced by 67 percent among patients who had responded to the drug during the initial 13-week dosing study.

Anakinra was approved by the U.S. Food and Drug Administration in 2001.  Its safety profile is based 14 years of clinical research.  Anakinra requires daily injections that frequently involve mild but painful injection site reactions.

[1] Larsen, C. M., M. Faulenbach, A. Vaag, A. Vølund, J. A. Ehses, B. Seifert, Mandrup-Poulsen, and M. Y. Donath. 2007. Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus. New Engl J Med 356:1517.