Elevated circulating fasting glucagon-like peptide-1 in surgical patients with aortic valve disease and diabetes

Abstract

BackgroundDiabetes is a risk factor for peripheral, coronary, and cerebrovascular disease. In contrast, results also indicate that patients with diabetes have reduced prevalence of aortic aneurysms, although the mechanisms remain largely unknown. We hypothesize that altered endogenous secretion of the intestinal hormone glucagon-like peptide-1 (GLP-1)—previously shown to protect from aneurysm formation, and governing many of the mechanisms thought to be involved in aneurysm formation—may provide insights into the mechanisms underlying the inverse relationship of diabetes and aneurysm.MethodsWe undertook a case–control study to characterize circulating plasma GLP-1 levels in diabetic and non-diabetic surgical patients with aortic valve disease, and with or without ascending aortic dilation. The cohort included patients with a bicuspid aortic valve (BAV), a common congenital disorder associated with ascending aortic aneurysm, as well as patients with a tricuspid aortic valve (TAV).ResultsIn our patient group, diabetes was characterized by a significant increase in fasting plasma GLP-1 levels. Further, we show that aortic dilation in these patients was associated with a significant increase in fasting plasma GLP-1, although a significant increase in the intact and bioactive peptide could not be detected in BAV patients with aortic dilation.ConclusionA subgroup of diabetic patients with aortic valve pathology have increased fasting plasma GLP-1 levels, which may be of importance for the low prevalence of aortic dilation in this patient group. Further, in TAV patients, GLP-1 secretion and plasma levels of intact GLP-1 are upregulated in association with aortic dilation, possibly indicating a compensatory mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-017-0279-0) contains supplementary material, which is available to authorized users.

Elevated Glucagon-like Peptide-1 and a Th2 Shift May Support Reduced Prevalence of Thoracic Aortic Aneurysm in Patients with Diabetes

“…In accordance with previous results [10], total F-GLP-1 (35.4 ± 3.1 vs. 19.0 ± 1.4 pmol/L p < 0.0001, Figure 3a) and active F-GLP-1 (3.4 ± 0.7 vs. 1.4 ± 0.2 pmol/L, p < 0.01, Figure 3b) were higher in the T2D group, compared with the control group. As expected, a significant correlation between active and total F-GLP-1 was detected (r = 0.5575, p < 0.01, Figure 3c).…”

“…However, the GLP-1 receptor is widely expressed, and direct effects of the peptide on vascular tissue have been demonstrated. Further, although GLP-1 secretion is stimulated by nutrient intake and fasting levels are low, increased fasting plasma GLP-1 (F-GLP-1) has been detected in T2D [10] and is implicated in higher rates of energy expenditure, fat oxidation, and cardioprotective effects [11].…”

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

“…As GLP-1 has been shown to regulate processes that control Sdc-1 expression [ 23 , 26 , 27 , 28 ] and as the fpGLP-1 levels were upregulated in patients with aortic valve pathology in association with T2D [ 30 ] ( Figure 3 A), we investigated the possible contribution of fpGLP-1 to the increased adventitial expression of Sdc-1 in T2D patients. The expression of GLP-1R was, as expected, detected in the adventitia, facilitating the direct effects of GLP-1 ( Figure 3 B).…”

Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes

“…The decreased activity of DPP4 in plasma is congruent with some studies, while it stands in contrast to others. Krizhanovskii et al showed increased GLP1 in plasma of patients with dilatation of the ascending aorta, which could imply a decreased DPP-4 activity, and other studies have found a decreased DPP-4 activity in the plasma of patients with chronic obstructive pulmonary disease, a disease that has been linked to AAA rupture [40][41][42]. However, Lu et al detected a significant increase in DPP-4 in plasma from patients with AAA compared with the control group [16].…”