Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Type 1 Diabetes Mellitus.
试验速览
- 阶段
- 2 期
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes for more than 5 years
- •Body mass index of > 25 kg/m2
- •Insulin requirement > 0.5 U/kg bodyweight
- •HbA1c>7.5%, stable glycemic control
排除标准
- •Inability to give informed consent
- •Presence of any medical condition that might interfere with the current study protocol.
- •Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids)
- •Anti-inflammatory drugs (including nonsteroidal anti-inflammatory drugs, 100 mg or less of aspirin per day is allowed)
- •Signs of current infection (fever, C-reactive protein (CRP) > 30 mmol/l, treatment with antibiotics, previous or current diagnosis of tuberculosis.
- •A history of recurrent infections
- •Pregnancy or breast-feeding (contraception of at least 3 months before inclusion is required for fertile women)
- •Liver disease (aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range)
- •Renal disease (creatinine > 130 µmol/l
- •Neutropenia < 2 x 109/l
研究组 & 干预措施
kineret
干预措施: kineret (Drug)
结局指标
主要结局
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
时间窗: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline
insulin sensitivity measured by euglycemic hyperinsulinemic clamp
次要结局
- glycemic control(baseline, after 1 week of treatment and 4 weeks after treatment termination)
- adipocyte insulin sensitivity(baseline, after 1 week of treatment, 4 weeks after treatment termination)
- circulating hormonal and inflammatory factors and lipid profile(baseline, after 1 week of treatment, 4 weeks after treatment termination)
- insulin sensitivity as determined by euglycemic hyperinsulinemic clamp(change in insulin sensitivity 4 weeks after stopping anakinra treatment as compared to baseline)