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 (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. 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 KNO3) 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 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 KNO3 vs. KCl (n = 33; P = 0.014 on ANOVA) with the effect driven by the high-dose cohort (24 mmol, n = 13; P 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 NO3- decreases insulin clearance. A likely mechanism is via NO-dependent inhibition of insulin-degrading enzyme.