Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure‐lowering

Article date: July 2019

By: Christopher N. Floyd, Satnam Lidder, Joanne Hunt, Sami A. Omar, Karen McNeill, Andrew J. Webb in Volume 85, Issue 7, pages 1443-1453


Dietary inorganic nitrate (NO3) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type 2 diabetes mellitus (T2DM). Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesized that acute physiological elevations in plasma [glucose]/[insulin] blunt the haemodynamic responses to NO3, a pertinent question for carbohydrate‐rich Western diets.


We conducted an acute, randomized, placebo‐controlled, double‐blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO3) vs. potassium chloride (KCl; placebo) administered 1 hour prior to an oral glucose tolerance test in 33 healthy volunteers.


Compared to placebo, there were no significant differences in systolic or diastolic BP (P = 0.27 and P = 0.30 on ANOVA, respectively) with KNO3, nor in pulse wave velocity or central systolic BP (P = 0.99 and P = 0.54 on ANOVA, respectively). Whilst there were significant elevations from baseline for plasma [glucose] and [C‐peptide], no differences between interventions were observed. A significant increase in plasma [insulin] was observed with KNO3vs. KCl (n = 33; P = 0.014 on ANOVA) with the effect driven by the high‐dose cohort (24 mmol, n = 13; P < 0.001 on ANOVA; at T = 0.75 h mean difference 210.4 pmol/L (95% CI 28.5 to 392.3), P = 0.012).


In healthy adults, acute physiological elevations of plasma [glucose] and [insulin] result in a lack of BP‐lowering with dietary nitrate. The increase in plasma [insulin] without a corresponding change in [C‐peptide] or [glucose] suggests that high‐dose NO3 decreases insulin clearance. A likely mechanism is via NO‐dependent inhibition of insulin‐degrading enzyme.

DOI: 10.1111/bcp.13913

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