Effect of Anakinra on Insulin Sensitivity in Type 1 Diabetes Mellitus
Recruitment status was: Recruiting
The purpose of this study is to test whether anakinra is able to reduce insulin resistance.
This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. By using this patient group, all positive effects on glycemic control should be the consequence of improved insulin sensitivity.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Type 1 Diabetes Mellitus.|
- insulin sensitivity as determined by euglycemic hyperinsulinemic clamp [ Time Frame: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline ] [ Designated as safety issue: No ]insulin sensitivity measured by euglycemic hyperinsulinemic clamp
- glycemic control [ Time Frame: baseline, after 1 week of treatment and 4 weeks after treatment termination ] [ Designated as safety issue: No ]HbA1c, fasting glucose
- adipocyte insulin sensitivity [ Time Frame: baseline, after 1 week of treatment, 4 weeks after treatment termination ] [ Designated as safety issue: No ]
- circulating hormonal and inflammatory factors and lipid profile [ Time Frame: baseline, after 1 week of treatment, 4 weeks after treatment termination ] [ Designated as safety issue: No ]
- insulin sensitivity as determined by euglycemic hyperinsulinemic clamp [ Time Frame: change in insulin sensitivity 4 weeks after stopping anakinra treatment as compared to baseline ] [ Designated as safety issue: No ]insulin sensitivity measured by euglycemic hyperinsulinemic clamp
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
once daily 100 mg of kineret subcutaneously for 8 days
Although typically associated with type 2 diabetes, insulin resistance has been documented in Type 1 diabetes. Insulin resistance may also play an important role in the pathophysiology of type 1 diabetes mellitus. Once diabetes has emerged chronically elevated glucose levels further induce insulin resistance (glucose toxicity).
Inflammation is an important link between obesity and insulin resistance. The mechanism of hyperglycemia-induced insulin resistance is not clear, but evidently must be related to high glucose levels. There are indications that chronic hyperglycemia can induce inflammation, for example hyperglycemia induces IL-1β release, and recent studies have shown an interaction with thioredoxin interacting protein (TXNIP), at the level of the beta-cell but also, as found by our own group, at the level of the adipose tissue
All together, these findings suggest that blocking IL-1β-receptor activation by the interleukin-1 receptor antagonist anakinra, may reverse insulin resistance associated both with obesity and/or chronic hyperglycemia. When applied in (hyperglycemic) subjects with type 2 diabetes, blocking IL-1β should diminish the effects of glucose toxicity both at the level of beta-cell function as at the level of insulin sensitivity. When applied in (hyperglycemic) subjects with type 1 diabetes, the effects of glucose toxicity at the level of insulin sensitivity should decrease.
In order to be able to study an isolated effect of IL-1β blockade on insulin sensitivity, this study will test this hypothesis in subjects with type 1 diabetes and hence provide a proof of principle in vivo in humans for a proposed link between hyperglycemia, inflammation and insulin resistance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285245
|Radboud University Nijmegen Medical Centre|
|Nijmegen, Netherlands, 6500HB|
|Principal Investigator:||Cees J Tack, MD PhD||Radboud University|