Effects of Nitrate on Liver Perfusion and Sugar Control

Hypothesis Inorganic nitrate from the diet, following conversion to nitrite and nitric oxide via the pathways described above will: 1. Increase hepatic microvascular perfusion 2. Increase GLP-1 secretion 3. Increase pancreatic insulin secretion 4. Reduce the area under the curve for glucose post meal Purpose To find out if inorganic nitrate found in green leafy vegetables protect against the risk of developing type 2 diabetes and cardiovascular disease by increasing hepatic microvascular perfusion and increasing incretin secretion. Aim The purpose of this study is to see if inorganic nitrate from the diet modulates hepatic perfusion and other pathways involved in post-prandial glucose homeostasis. MRI Hepatic micro vessel perfusion of the liver and portal vein diameter will be measured by Dr. Jon Fulford at the Peninsula Magnetic Resonance Research Centre, St Luke's Campus. Following initial survey images to obtain anatomical information apparent diffusion coefficients (ADC) are calculated in the posterior right lobe of the liver. Diffusion images are acquired with a single shot echo-planar imaging (EPI) sequence with 15 directions and b values of 200 and 800 s mm-2. Images are acquired during a single breathe-hold at an axial-oblique orientation with a repetition time (TR) of 1500 ms an echo time of 57 ms, an in-plane resolution of 4 x 4 mm and a slice thickness of 10 mm with fat suppression and 3 signal averages. ADC is given by: ADC = 1/(b200-b800) Ln (S800/S200) where S800 is the signal with a diffusion b-value of 800 s mm-2 (b800) and S200 is the signal with a diffusion b-value of 200 s mm-2 (b200). Statistical analysis Statistical analysis will be performed by an experienced and trained researcher and statistical advice will be available from Prof. Angela Shore from within the team and Beverly Shields from the NIHR Exeter Clinical Research Facility. Data will be assessed for normality. Depending on the normality of data the differences between the groups will be assessed by either unpaired t-test or Mann-Whitney test. Sample Size Sixteen participants would need to be recruited per group in order to detect a 1SD difference between groups data with 80% power and an a of 0.05. Twenty participants would be recruited in order to account for drop outs.