Glucagon-like peptide-1 secretory function as an independent determinant of blood pressure: analysis in the Tanno-Sobetsu study

Abstract

Aims: Roles 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 results: We 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.

Conclusions: The 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.

Figure 1. Relationship between blood pressure and AUC_GLP-1.

AUC_GLP-1 was weakly correlated with SBP (r = −0.26, p = 0.0085, Panel A). However, a significant correlation was not observed for the AUC_GLP-1– DBP relationship (Panel B). SBP, systolic blood pressure; DBP, diastolic blood pressure; AUC_GLP-1, area under the curve of GLP-1 level in the oral glucose tolerance test.

Figure 2. Blood pressure - AUC_GLP-1 relationships in the high and low AUC_GLP-1 groups.

In the high AUC_GLP-1 group, neither SBP nor DBP correlated with AUC_GLP-1 (Panels A and B). In contrast, there were significant correlations between AUC_GLP-1 and SBP (r = −0.40, p = 0.0032, Panel C) and between AUC_GLP-1 and DBP (r = −0.28 p = 0.0448, Panel D) in the low AUC_GLP-1 group. SBP, systolic blood pressure; DBP, diastolic blood pressure; AUC_GLP-1, area under the curve of GLP-1 level in the oral glucose tolerance test.

Figure 3. Time courses of PG and IRI in the OGTT.

Broken lines and solid lines indicate the low AUC_GLP-1 group and high AUC_GLP-1 group, respectively. The low AUC_GLP-1 group showed significantly higher PG level at 60 min after glucose loading than in the high AUC_GLP-1 group (Panel A). *p = 0.039. There was no inter-group difference in time courses of plasma IRI during the OGTT (Panel B). PG, plasma glucose; IRI, immunoreactive insulin.