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

Aims Dietary inorganic nitrate (NO 3 − ) 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 NO 3 − , a pertinent question for carbohydrate‐rich Western diets. Methods We conducted an acute, randomized, placebo‐controlled, double‐blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO 3 ) vs . potassium chloride (KCl; placebo) administered 1 hour prior to an oral glucose tolerance test in 33 healthy volunteers. Results Compared to placebo, there were no significant differences in systolic or diastolic BP ( P =  0.27 and P  = 0.30 on ANOVA, respectively) with KNO 3 , 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 KNO 3 vs . 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). Conclusions 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 NO 3 − decreases insulin clearance. A likely mechanism is via NO‐dependent inhibition of insulin‐degrading enzyme.