Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures

Julie R Lundgren, Kristine Færch, Daniel R Witte, Anna E Jonsson, Oluf Pedersen, Torben Hansen, Torsten Lauritzen, Jens J Holst, Dorte Vistisen, Marit E Jørgensen, Signe S Torekov, Nanna B Johansen, Julie R Lundgren, Kristine Færch, Daniel R Witte, Anna E Jonsson, Oluf Pedersen, Torben Hansen, Torsten Lauritzen, Jens J Holst, Dorte Vistisen, Marit E Jørgensen, Signe S Torekov, Nanna B Johansen

Abstract

Background and aim: Cardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD.

Methods: This cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m2, without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex.

Results: A greater GLP-1 response was associated with lower central systolic and diastolic BP of - 1.17 mmHg (95% confidence interval (CI) - 2.07 to - 0.27 mmHg, P = 0.011) and - 0.74 mmHg (95% CI - 1.29 to - 0.18 mmHg, P = 0.009), respectively, as well as lower brachial systolic and diastolic BP of - 1.27 mmHg (95% CI - 2.20 to - 0.33 mmHg, P = 0.008) and - 1.00 (95% CI - 1.56 to - 0.44 mmHg, P = 0.001), respectively. PWV was not associated with GLP-1 release (P = 0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: - 4.94 (95% CI - 8.56 to - 1.31) mmHg, central diastolic BP: - 3.05 (95% CI - 5.29 to - 0.80) mmHg, brachial systolic BP: - 5.18 (95% CI - 8.94 to - 1.42) mmHg, and brachial diastolic BP: - 2.96 (95% CI - 5.26 to - 0.67) mmHg).

Conclusion: Greater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality. Trial registration ClinicalTrials.gov Identifier: NCT00237549. Retrospectively registered 10 October 2005.

Keywords: Aortic stiffness; Cardiovascular disease; Central blood pressure; GLP-1; Peripheral blood pressure.

Conflict of interest statement

TL holds shares in Novo Nordisk. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Oral glucose tolerance test (OGTT) responses of glucagon-like peptide-1 (GLP-1), glucose and insulin. Median is shown by a square and brackets show interquartile range
Fig. 2
Fig. 2
Estimated difference in blood pressure measures in 837 individuals for a doubling in incremental AUC (iAUC) of GLP-1. HOMA-IR homeostatic model assessment for insulin resistance, BMI body mass index

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