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

INTRODUCTION: Dietary inorganic nitrate (NO3- ) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type two diabetes mellitus. Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesised 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, randomised, placebo-controlled, double-blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO3 ) versus potassium chloride (KCl; placebo) administered 1 h 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 versus KCl (n=33; P=0.014 on ANOVA) with the effect driven by the high-dose cohort (24mmol, 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 NO3- decreases insulin clearance; a likely mechanism is via NO-dependent inhibition of insulin-degrading enzyme.