Glucagon-Like Peptide-1 Secretory Function as an Independent Determinant of Blood Pressure: Analysis in the Tanno-Sobetsu Study

Abstract

AimsRoles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation.Methods and ResultsWe recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUCGLP-1), an index of GLP-1 secretory function. Multiple linear regression analysis indicated that AUCGLP-1 was an independent negative predictor of systolic BP (SBP), while AUCGLP-1 was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUCGLP-1 to divide the study subjects into high and low GLP-1 response groups, AUCGLP-1 was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group.ConclusionsThe results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.

Plasma levels of glucagon‐like peptide 1 and markers of obesity among young and healthy adults

“…Prior population-based studies on the relationship between fasting GLP-1 and BMI have mostly been small and did not show a significant relationship. 13,14,28 Our study was able to show a significant relationship between GLP-1 and BMI. However, after adjusting for body fat mass, this relationship did not remain significant, suggesting that a large amount of the observed relationship was due to body fat mass.…”

“…Prior population‐based studies on the relationship between fasting GLP‐1 and BMI have mostly been small and did not show a significant relationship . Our study was able to show a significant relationship between GLP‐1 and BMI.…”

“…7 However, whether fasting GLP-1 levels in healthy individuals are related to measures of obesity is less clear, and only few mainly small studies have been published. Most studies evaluating the association of GLP-1 with BMI were negative, 13,14 but one small study found an inverse relationship between GLP-1 and waist circumference. 15 Lower GLP-1 levels after weight loss among obese individuals were observed in some 16,17 but not all studies.…”

Glucagon-Like Peptide-1 and Blood Pressure in Young and Healthy Adults from the General Population

“…The only previous study investigating the relationship of GLP-1 with BP did not find a significant relationship, which could potentially be explained by the relatively small sample size of 128 study subjects and the absence of ambulatory BP measurement in the earlier study. 33 Other previous studies have mainly assessed the effect of GLP-1 RA or infusions on BP. Some of these studies found a reduction in BP levels with these interventions.…”

Selective targeting of glucagon‐like peptide‐1 signalling as a novel therapeutic approach for cardiovascular disease in diabetes

“…Indeed, heart rate, which is not linked to body weight, was increased by chronic administration of both liraglutide and exenatide in T2DM patients in parallel with reduced systolic BP (Garber et al ., ; Gill et al ., ). Interestingly, it was recently reported that GLP‐1 secretory function increases with age and is negatively correlated with systolic BP, suggesting that this may represent an adaptive response (Yoshihara et al ., ).…”