Different Pharmacokinetic Responses to an Acute Dose of Inorganic Nitrate in Patients with Type 2 Diabetes

Aim: In this study, we aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. Methods: Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3 were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured. Results: Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 μmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 μmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal. Conclusion: T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3 supplementation.