Diabetes Mellitus Type 2, Glucose Intolerance, Impaired Insulin Secretion
Conditions
Brief summary
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.
Interventions
DRUGAnakinra
150 mg sc once daily during four weeks
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the effect of anakinra on insulin secretion, as derived from hyperglycemic clamps . | after 4 weeks of treatment with anakinra |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine the effect on anakinra on insulin sensitivity. | after 4 week treatment of anakinra | Oral glucose tolerance test |
| Effects of anakinra on fat cell morphology and gene expression | after 4 weeks of treatment with anakinra | Fatbiopsy |
Countries
Netherlands
Outcome results
None listed