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.

目的：在这项研究中，我们旨在比较2型糖尿病（T2DM）患者和健康成年人中硝酸盐（NO ₃）的药代动力学。还评估了唾液硝酸还原酶（NR）活性对急性剂量NO _3的心脏代谢反应的潜在影响。

方法：招募9名健康成年人和9名T2DM患者食用富含NO _3的早餐（〜410 mg NO ₃）。通过在8小时内重复测量血清和唾液中NOx（硝酸盐+亚硝酸盐）的浓度以及现场和24小时尿液样本中NO _3的浓度，来检查NO _3的药代动力学。还测量了心脏代谢参数，包括血清葡萄糖，胰岛素和甘油三酸酯的水平以及血压。

结果：与2型糖尿病患者，血清NOx浓度（Δ ₁健康受试者的= 16.7与4.4微摩尔/ L，P = 0.057）后急剧NO 1小时内增加₃加载。健康受试者的NR活性指数较高，唾液中NO _3的峰值浓度较高，而到达峰值的时间较短。高NR值与低NR值的糖尿病患者全身NOx暴露较高（103±31.4 vs. 58.9±22.1μmol.h/ L）；摄入富含NO _3的食物后，他们还表现出更好的血糖反应和更多的血压降低。

结论：T2DM可能与NOx药代动力学的不同模式（尤其是唾液NOx代谢）有关。唾液NR活性可能在餐后NO ₃代谢中起关键作用，而具有较高NR活性的糖尿病患者可能会从NO ₃补充中获得更多好处。