Acid-base status and the development of hypertension and diabetes

摘要 最近的数据表明，酸碱状态的微小变化可能在发展中发挥重要作用， 高血压和2型糖尿病。较低的pH值可能会导致高血压，通过促进肾盐- 滞留，并可能通过抑制胰岛素与其受体的结合而导致胰岛素抵抗。健康 参与国家健康和营养检查调查的人，他们有血压，空腹血糖， 和血浆碳酸氢盐在正常范围内，较低的碳酸氢盐与较高的血液 高血压和更大的胰岛素抵抗，独立于身体大小和肾功能。因为碳酸氢盐是 作为细胞外液中的主要缓冲剂，较低的血浆碳酸氢盐通常反映较低的细胞外pH。 作为对酸产生的代偿反应的一部分，肾脏减少了在肾脏中损失的柠檬酸盐的量。 尿-我们以前报告过护士健康研究（NHS）参与者的24小时尿柠檬酸盐较低， 高血压高碱饮食（如DASH饮食）降低血压，观察性研究 报告说，较高的膳食钾（碱摄入量的标志）与糖尿病的风险较低有关。 因为以前的人体研究检查酸碱状态，高血压， 糖尿病是横断面的，目前尚不清楚低度代谢性酸中毒是一个原因还是一个 这些疾病的后果。为了确定酸碱状态与血液流变学之间的独立联系， 随后的高血压和2型糖尿病的风险，我们提出了以下前瞻性研究的妇女 在NHS I和II中：1）一项关于血浆碳酸氢盐与以下风险之间关系的巢式病例对照研究： 高血压事件（N = 1500），2）24小时尿柠檬酸盐与风险之间相关性的队列研究 3）一项关于血浆碳酸氢盐与高血压发病率（N = 2000）之间关系的队列研究， 非糖尿病女性胰岛素抵抗的变化（N = 750），以及4）一项巢式病例对照研究， 血浆碳酸氢盐与糖尿病发病风险之间的关系（N = 1500）。 这一建议代表了第一次大规模的前瞻性努力，以检查酸碱状态的影响 高血压、胰岛素抵抗和2型糖尿病的风险。这种独特的优势 应用程序包括1）更新，详细的接触信息积累了长期的前瞻性，2） 存档血浆，和3）提供高统计功效的大样本量。

Abstract Recent data suggest that small changes in acid-base status may play an important role in the development of hypertension and type 2 diabetes. Lower pH may result in higher blood pressure by promoting renal salt- retention and may lead to insulin resistance by inhibiting binding of insulin to its receptors. In healthy participants of the National Health and Nutrition Examination Survey who had blood pressure, fasting glucose, and plasma bicarbonate in ranges considered normal, lower bicarbonate was associated with higher blood pressure and greater insulin resistance, independent of body size and kidney function. Because bicarbonate is the primary buffer in extra-cellular fluid, lower plasma bicarbonate generally reflects lower extra-cellular pH. As part of the compensatory response to acid production, the kidney decreases the amount of citrate lost in the urine - and we previously reported lower 24-hour urinary citrate in Nurses Health Study (NHS) participants with hypertension. High alkali diets (such as the DASH diet) reduce blood pressure, and observational studies report that higher dietary potassium (a marker of alkali intake) is associated with a lower risk of diabetes. Because previous human studies examining the relations between acid-base status, hypertension, and diabetes were cross-sectional, it is unknown whether low-grade metabolic acidosis is a cause or a consequence of these diseases. To determine the independent associations between acid-base status and the subsequent risk of hypertension and type 2 diabetes, we propose the following prospective studies of women in NHS I and II: 1) a nested case-control study of the association between plasma bicarbonate and risk of incident hypertension (N = 1500), 2) a cohort study of the association between 24-hour urinary citrate and risk of incident hypertension (N = 2000), 3) a cohort study of the association between plasma bicarbonate and changes in insulin resistance in women without diabetes (N = 750), and 4) a nested case-control study of the relation between plasma bicarbonate and risk of incident diabetes (N = 1500). This proposal represents the first large-scale prospective effort to examine the impact of acid-base status on the risk of developing hypertension, insulin resistance, and type 2 diabetes. The unique strengths of this application include 1) updated, detailed exposure information accumulated prospectively over long periods, 2) archived plasma, and 3) large sample sizes providing high statistical power.