The Effect of Sitagliptin on Hypertension, Arterial Stiffness, Oxidative Stress and Inflammation
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- arterial stiffness, defined as change in augmentation index measured by means of a non-invasive technique using the commercially available SphygmoCor System, and the results of the 24 hour blood pressure monitoring
研究概览
简要总结
Recently a new category of antihyperglycemic therapy aiming to modulate the incretin system has emerged. These drugs induce insulin secretion without inducing hypoglycemia. The effect of the incretin modulators drugs on hypertension, arterial stiffness, inflammation and oxidative stress parameters have not been fully investigated yet.GLP-1 analogue has been suggested to have an effect on endothelium and the development of hypertension. Nystrom et al have demonstrated that GLP-1 improves endothelial dysfunction in a small group of type 2 diabetes subjects, with coronary heart disease. We hypothesize that DPP-4 inhibitor will have an effect on hypertension and arterial stiffness by effect on the NO pathway.The aim of this study is to investigate the effect of two insulin inducers drugs, sulfonyl urea and DPP-4 inhibitor on 24 hours blood pressure monitoring, arterial stiffness, oxidative stress and inflammation.
详细描述
Background:
Recently, a new category of hypoglycemic therapy has emerged, aimed to modulate the incretin system in diabetic patients. Compared to other drugs that induce insulin secretion, these agents do not cause hypoglycemia. However, until now the differential effects of incretin modulators and the classical insulin inducers on hypettension, arterial stiffness, inflammation and oxidative stress parameters have not been yet investigated.
Incretins The increase in plasma insulin levels following oral administration of glucose usually exceeds the levels observed after intravenous glucose administration. The phenomenon is defined as incretin effect and has been attributed to the intestinal hormones which are released after oral glucose administration. The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1).
Incretin effect is reduced in type-2 diabetic patients. After oral glucose administration, both GIP and GLP-1 are secreted and rapidly inactivated by an enzyme dipeptidyl peptidase 4 (DPP-4). Accordingly, the half-life of active GLP-1 is less than 2 min (2). Both GIP and GLP-1 stimulate insulin secretion in a glucose-dependent manner. Moreover, GLP-1 has also been shown to increase islet cell neogenesis and differentiation, as well as reduce apoptosis of β-cells in rodents. (3-5). Incretins also affect glucagon secretion. GIP stimulates glucagon production (6) ,whereas GLP-1 inhibits synthesis of the latter (7). Differential effects of the two peptides on glucagon secretion may prove responsible for normalization of blood glucose after intravenous injection of GLP-1 but not after administration of GIP or its derivatives [7, 8]. Therefore, GLP-1 is the only incretin that has been applied for treatment for diabetes.
In addition to its direct insulin/glucagons activities, GLP-1 has other extra-pancreatic effects:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diabetic patients
- •aged 18 years or older
- •treated with metformin
- •Only patients with HbA1C levels within the range 7% - 11% will be enrolled in the study
排除标准
- •A history of treatment with incretins or sulfonylurea during the last 3 months
- •Treatment with nitrates
- •Uncontrolled heart failure
- •Uncontrolled hypertension and/or any change in the hypertensive medications within one month prior starting the study
- •No proven regular treatment with aspirin or statins within one month prior starting the study
- •Any malignancy with life expectancy of less then 1 year
- •pregnancy
研究组 & 干预措施
A
diabetic patients who are treated with metformin wiyh HBA1C>7% will get sitagliptin
干预措施: sitagliptin (Drug)
B
diabetic patients who are treated with metformin with HBA1C>7% will get glibenclamide
干预措施: glibenclamide (Drug)
结局指标
主要结局
arterial stiffness, defined as change in augmentation index measured by means of a non-invasive technique using the commercially available SphygmoCor System, and the results of the 24 hour blood pressure monitoring
时间窗: 6 months
次要结局
- The secondary end results would be oxidative stress parameters, as evaluated by oxidized LDL and Isoprostanes, and markers of inflammatory status, including measurements of pro-inflammatory interleukins and performance of highly sensitive CRP test.(6 months)