The Effect of Anakinra on Insulin Secretion

The Effect of Interleukin-1 Receptor Antagonist on Insulin Secretion in Subjects With Beta Cell Dysfunction

Rationale: Once diabetes develops, β-cell function progressively deteriorates and therapeutic approaches that prevent of delay loss of β-cell function are needed in the treatment of type 2 diabetes mellitus. Recent findings suggest that interleukin-1 (IL-1) may be involved in the progressive β-cell dysfunction in type 2 diabetes mellitus.

Objective: to determine whether blocking IL-1β by recombinant human IL-1ra (anakinra) improves beta-cell function in subjects with β-cell dysfunction.

Inclusion Criteria:

• Impaired glucose tolerance assessed by oral glucose tolerance test and/or impaired fasting glucose ( ≥ 5.6 mmol/L) and/or HbA1c levels of 5.7-6.4%
• BMI >25 kg/m2
• Age 40-70 years

Exclusion Criteria:

• Known diabetes mellitus
• Fasting plasma glucose ≥ 7.0 mmol/L or HbA1c ≥ 6.5%
• Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids)
• Use of anti-inflammatory drugs ( including corticosteroids and non steroidal anti-inflammatory drugs, 100 mg or less of aspirin is allowed)
• Signs of current infection (fever, C-reactive protein >30 mmol/L, treatment with antibiotics, previous or current diagnosis of tuberculosis)
• A history of recurrent infections
• Pregnancy or breastfeeding (contraception of at least 3 months before inclusion is required)
• Liver disease defined as aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range
• Renal disease defined as MDRD < 60 ml/min/1.73m2
• Neutropenia < 2x 109/L
• Inability to understand the nature and extent of the trial and the procedures required.
• Any medical condition that might interfere with the current study protocol
• Participation in a drug trial within 60 days prior to the first dose