Effects of exenatide on postprandial vascular endothelial dysfunction in type 2 diabetes mellitus

Abstract

BackgroundBasic studies have shown that glucagon-like peptide-1 (GLP-1) analogs exert a direct protective effect on the vascular endothelium in addition to their indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are also reported to inhibit postprandial vascular endothelial dysfunction. This study examined whether the GLP-1 analog exenatide inhibits postprandial vascular endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM).MethodsSeventeen patients with T2DM underwent a meal tolerance test to examine changes in postprandial vascular endothelial function and in glucose and lipid metabolism, both without exenatide (baseline) and after a single subcutaneous injection of 10 μg exenatide. Vascular endothelial function was determined using reactive hyperemia index (RHI) measured by peripheral arterial tonometry before and 120 min after the meal loading test. The primary endpoint was the difference in changes in postprandial vascular endothelial function between the baseline and exenatide tests.ResultsThe natural logarithmically-scaled RHI (L_RHI) was significantly lower after the baseline meal test but not in the exenatide test. The use of exenatide resulted in a significant decrease in triglycerides (TG) area under the curve and coefficient of variation (CV). The change in L_RHI correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate analysis identified changes in triglyceride CV as the only determinant of changes in L_RHI, contributing to 41% of the observed change.ConclusionsExenatide inhibited postprandial vascular endothelial dysfunction after the meal loading test, suggesting that exenatide has a multiphasic anti-atherogenic action involving not only glucose but also lipid metabolism.Trial registrationClinicalTrials.gov: UMIN000015699.

GLP-1–Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus

“…Interestingly, infusion of exenatide increased power in the endothelial domain of vasomotion. This corresponds with the observation that a single subcutaneous dose of exenatide prevents postprandial endothelial dysfunction in subjects with prediabetes or diabetes mellitus, 39,40 when measured by reactive hyperemia applanation tonometry. However, because we observed no exenatide changes in capillary perfusion or total vasomotion in current trial, it is unclear whether the improvement in endothelial power has physiological relevance.…”

Effects of linagliptin monotherapy compared with voglibose on postprandial lipid profiles in Japanese patients with type 2 diabetes: linagliptin study of effects on postprandial blood glucose (L-STEP) sub-study 1

“…Furthermore, we previously reported that highfat diet loading reduced vascular endothelial function in patients with type 2 diabetes, suggesting that the existence of postprandial hyperlipidemia may facilitate the progression of endothelial dysfunction [22]. Also we showed in patients with type 2 diabetes that the diet loading test resulted in a significant decrease in vascular endothelial function, which correlated with TG AUC [7]. In healthy adult volunteers, a cookie load decreased FMD in a manner that correlated significantly with variations in TG and apoB-48 [21].…”

“…While previous studies showed that high levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglyceride (TG) were associated with increased cardiovascular events in patients with T2DM [1,2], many studies revealed that postprandial dyslipidemia was an also independent risk factor for cardiovascular diseases such as coronary artery disease [3], carotid atherosclerosis [4], sudden death [5], and stroke [6]. Indeed, in our previous study, we found that decreased endothelial function in patients with T2DM during meal load was strongly correlated with postprandial TG levels, but not postprandial glucose levels [7]. Apolipoprotein B48 (ApoB48) is one of several intestinally derived lipoproteins.…”

“…Effects of linagliptin monotherapy compared with voglibose on postprandial lipid profiles in Japanese patients with type 2 diabetes: linagliptin study of effects on postprandial blood glucose (L-STEP) sub-study 1 Akira Kurozumi 1) , Yosuke Okada 1) , Hiroaki Satoh 2) , Ikuo Inoue 3) , Hiroko Chimori 4) , Etsuko Akita 5) , Toshihiko Shiraiwa 6) , Yoshio Fujitani 2) , Tomoya Mita 2) , Masahiko Gosho 7) and Hirotaka Watada 2) patients with T2DM. While previous studies showed that high levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglyceride (TG) were associated with increased cardiovascular events in patients with T2DM [1,2], many studies revealed that postprandial dyslipidemia was an also independent risk factor for cardiovascular diseases such as coronary artery disease [3], carotid atherosclerosis [4], sudden death [5], and stroke [6].…”

Acarbose Accelerates Wound Healing via Akt/eNOS Signaling indb/dbMice

“…The postprandial surge of plasma glucose could lead to severe endothelial dysfunction in diabetic patients [16–18]. Clinical researches have shown that the administration of acarbose improved endothelial function and reduced the risk of cardiovascular events in patients with T2DM [19–21].…”