Effects of a Chronical Treatment With Benfotiamine in People With Type 2 Diabetes Mellitus on Pre- and Postprandial Endothelial Function, as Well as on the Function of the Autonomic Nervous System
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Endothelial function (flow mediated dilatation - ultrasound- and reactive hyperemia- laser doppler-)
研究概览
简要总结
An AGE-rich diet can induce after 2-6 weeks persistent increases in mediators linked to vascular dysfunction (e.g. TNFα, VCAM-1) in people with type 2 diabetes mellitus (T2DM). Benfotiamine (BT), the liposoluble derivative of vitamin B1, blocks several pathways common to hyperglycaemia- and AGE-induced endothelial dysfunction. We have shown that advanced glycation end products (AGE) of a regular mixed meal can acutely induce vascular dysfunction in T2DM and that this effects can be prevented by a three days pretreatment with BT.
The hypotheses of this study are that chronical treatment with benfotiamine (900 mg/day for 6 weeks) in people with type 2 diabetes mellitus:
- prevents postprandial impairment of endothelial function after a high-AGE meal.
- Improves fasting endothelial function.
- Improves parameters of autonomic function in fasting and postprandial state.
- Improves insulin sensitivity and prevents postprandial increase in insulin resistance.
详细描述
People with type 2 diabetes mellitus (T2DM) have a two to fivefold increase in cardiovascular mortality compared to non-diabetic controls.
Endothelial dysfunction (ED) is an early messenger of atherosclerosis and is responsible for increased vascular permeability, platelet aggregation and adhesion, leucocyte adhesion and smooth muscle cell proliferation and favours a vasoconstrictive and pro-inflammatory state.
Postprandial ED occurs not only in patients with CV disease or diabetes, but even in healthy subjects. Distinctive and cumulative effects of hyperglycemia and hypertriglyceridemia on postprandial ED have been demonstrated. Since postprandial dysmetabolism was linked to CV disease, the postprandial ED was proposed to be the mechanism connecting them. Considering that the postprandial state covers most of our daytime, interventions targeting a reduction in postprandial ED might play a decisive role in atherosclerosis prevention.
For the treatment of postprandial ED several therapeutical approaches have been suggested, such as treatment with folic acid, tetrahydrobiopterin, vitamins C and E,statins etc.
These approaches aim at reducing postprandial oxidative stress (vitamins C and E, statins and partly folic acid), postprandial hyperglycemia (insulin), postprandial hypertriglyceridemia (statins) or have a direct effect on endothelial NO production (folic acid, insulin and tetrahydrobiopterin).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •People with type 2 diabetes mellitus
- •Age: 30-70 years
排除标准
- •History of myocardial infarction, stroke within the previous 6 months
- •Heart failure NYHA III or more
- •Malignant disease
- •Severe diabetes complications
- •Severe hypo- or hypertension
- •Chronic alcohol abuse
- •Renal failure (creatinine >2mg/dl)
研究组 & 干预措施
A1
Benfotiamine
干预措施: Benfotiamine (Drug)
A2
干预措施: Placebo (Drug)
结局指标
主要结局
Endothelial function (flow mediated dilatation - ultrasound- and reactive hyperemia- laser doppler-)
时间窗: September 2007- December 2008
次要结局
- Parameters of autonomic neuropathy(September 2007- December 2008)