Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals
试验速览
- 阶段
- 2 期
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp
研究概览
简要总结
Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance.
Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Earlier it has been shown that interleukin-1 receptor antagonist in human subjects improves glycemic control. The investigators' hypothesis is that this is due to improved insulin sensitivity.
详细描述
The prevalence of obesity is increasing fast. Obesity is one of the most common acquired risk factors for insulin resistance. As a consequence the prevalence of type 2 diabetes mellitus is rising fast as well.
Interleukin 6 and Tumor Necrosis Factor alfa are well known pro-inflammatory cytokines that have been linked to insulin resistance. Results from our own group show that interleukin-1 is also involved in the process of developing insulin resistance.
Earlier research projects studied the effect of Interleukin-1 receptor antagonist (Anakinra) on glycemic control in subjects with type 2 diabetes mellitus. It was shown that glycemic control was improved. The authors conclude that this is the result of improved function of pancreatic beta cells.
These results are in contrast to our results of in vitro en in vivo research on mice, which show improved insulin sensitivity by Interleukin-1 receptor antagonist.
A possible explanation for not finding an effect on insulin sensitivity by earlier research projects may be that it is difficult to reliable quantify insulin sensitivity in this group of patients with concurrent changes in glycemic control, extensive co-morbidity and medication use, who might be at the rather extreme end of insulin resistance. Furthermore a relatively low dose of Anakinra was used.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •adult subjects with a BMI > 30 kg/m2
- •3 or more characteristics of the metabolic syndrome
排除标准
- •inability to give informed consent
- •age < 18 years
- •known diabetes mellitus
- •fasting plasma glucose > 7,0 mmol/l or HbA1c > 6,2%
- •presence of any medical condition that might interfere with the current study protocol
- •immunodeficiency of immunosuppressive treatment
- •anti-inflammatory drugs (100 mg of aspirin/day is allowed)
- •signs of current infection
- •history of recurrent infections
- •pregnancy or breast feeding
- •liver disease
- •renal disease
- •neutropenia
研究组 & 干预措施
Anakinra group
Anakinra 150 mg/day during four weeks
干预措施: Anakinra (Kineret) (Drug)
Placebo
Placebo during four weeks
干预措施: Placebo (Drug)
结局指标
主要结局
to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp
时间窗: after four weeks of treatment
次要结局
- pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio(after four weeks of treatment)
- lipid profile(after four weeks of treatment)
- systemic inflammation(after four weeks of treatment)