Effects of Acarbose on GLP-1 in Newly Diagnosed T2D Patients
Effects of Acarbose on GLP-1 in Newly Diagnosed T2D Patients
Type 2 diabetes (T2D) is known to dramatically increase the risk of cardiovascular disease, such as angina pectoris and myocardial infarction, and it is believed that hyperglycemia itself, especially postprandial hyperglycemia, is an independent risk factor for such diseases. The previous studies have shown that treatment with acarbose, an alpha-glucosidase inhibitor (AGI), is associated with a significant reduction in cardiovascular events in a population with T2D and impaired glucose tolerance (IGT). However, the underlying mechanisms of this effect are unclear. Recently, new insights into the possible actions of acarbose on cardiovascular risks have been provided by the incretin concept. Following the intake of AGIs, large amounts of undigested carbohydrates reach the lower portion of the small intestine, which is rich in L-cells that produce glucagon-like peptide 1 (GLP-1) and therefore stimulate a long-lasting increased secretion of GLP-1. GLP-1 can elevate levels of nitric oxide (NO), which is the most important endothelium-derived vasodilator and has a potent anti-atherosclerotic effect in the coronary effluent from mouse hearts. Moreover, a recent animal study suggests that voglibose (another AGI) can reduce myocardial infarct size through the stimulation of GLP-1 receptors and the activation of the phosphoinositide 3-kinase-Akt-endothelial NOS pathways.
To date, the majority of studies have evaluated the short-term effects of acarbose treatment (up to 2 weeks) on GLP-1; the long-term effects of AGIs on NO and NOS in T2D have not been extensively investigated. In the present study, we aimed to explore whether levels of serum GLP-1 and NO and NOS activity increase following chronic (24 weeks) treatment with acarbose monotherapy in newly diagnosed patients with T2D. We also aimed to evaluate the effect of acarbose on carotid atherosclerosis (as defined by carotid intima-media thickness [CIMT]). It is known that CIMT has an important prognostic value with respect to the development of both cardiovascular diseases and of atherosclerotic lesions in the carotid and peripheral arteries.
Background
Type 2 diabetes (T2D) is known to dramatically increase the risk of cardiovascular disease, such as angina pectoris and myocardial infarction, and it is believed that hyperglycemia itself, especially postprandial hyperglycemia, is an independent risk factor for such diseases. The previous studies have shown that treatment with acarbose, an alpha-glucosidase inhibitor (AGI), is associated with a significant reduction in cardiovascular events in a population with T2D and impaired glucose tolerance (IGT). However, the underlying mechanisms of this effect are unclear. Recently, new insights into the possible actions of acarbose on cardiovascular risks have been provided by the incretin concept. Following the intake of AGIs, large amounts of undigested carbohydrates reach the lower portion of the small intestine, which is rich in L-cells that produce glucagon-like peptide 1 (GLP-1) and therefore stimulate a long-lasting increased secretion of GLP-1. GLP-1 can elevate levels of nitric oxide (NO), which is the most important endothelium-derived vasodilator and has a potent anti-atherosclerotic effect in the coronary effluent from mouse hearts. Moreover, a recent animal study suggests that voglibose (another AGI) can reduce myocardial infarct size through the stimulation of GLP-1 receptors and the activation of the phosphoinositide 3-kinase-Akt-endothelial NOS pathways.
To date, the majority of studies have evaluated the short-term effects of acarbose treatment (up to 2 weeks) on GLP-1; the long-term effects of AGIs on NO and NOS in T2D have not been extensively investigated. In the present study, we aimed to explore whether levels of serum GLP-1 and NO and NOS activity increase following chronic (24 weeks) treatment with acarbose monotherapy in newly diagnosed patients with T2D. We also aimed to evaluate the effect of acarbose on carotid atherosclerosis (as defined by carotid intima-media thickness [CIMT]). It is known that CIMT has an important prognostic value with respect to the development of both cardiovascular diseases and of atherosclerotic lesions in the carotid and peripheral arteries.
Source...