Abstract

BackgroundTreatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D).MethodsBlood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily).ResultsFollowing 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels.ConclusionsTwenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

Highlights

  • Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events

  • We aimed to explore whether levels of serum glucagon-like peptide 1 (GLP-1) and nitric oxide (NO) and nitric oxide synthase (NOS) activity increase following chronic (24 weeks) treatment with acarbose monotherapy in newly diagnosed patients with type 2 diabetes (T2D)

  • Our study indicates that chronic acarbose therapy is associated with a significant increase in both fasting and postprandial active GLP-1 levels in newly diagnosed patients with T2D

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Summary

Introduction

Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. We examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). The previous studies have shown that treatment with acarbose, an alpha-glucosidase inhibitor (AGI), is associated with a significant reduction in cardiovascular mouse hearts [11]. 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-Aktendothelial NOS pathways [12]. 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. 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 [13,14]

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