Acid-base status and the development of hypertension and diabetes

酸碱状态与高血压和糖尿病的发生

• 批准号: 7892274
• 负责人: ERIC N TAYLOR
• 金额: $ 36.26万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7892274
• 关键词: Acids; Affect; Alkalies; Animals; Archives; Bicarbonates; Binding; Blood Pressure; Body Size; Buffers; Cardiovascular Diseases; Cause of Death; Chronic Kidney Failure; Citrates; Cohort Studies; Cross-Sectional Studies; DASH diet; Data; Development; Diabetes Mellitus; Diet; Dietary Potassium; Disease; Excretory function; Fasting; Goals; Hour; Human; Hypertension; Individual; Insulin; Insulin Resistance; Intake; Kidney; Kidney Failure; Lead; Liquid substance; Metabolic acidosis; Modeling; National Health and Nutrition Examination Survey; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Observational Study; Oral; Participant; Plasma; Play; Preventive Intervention; Production; Prospective Studies; Public Health; Rattus; Recording of previous events; Renal function; Reporting; Risk; Risk Factors; Role; Sample Size; Sodium Bicarbonate; Sodium Chloride; Triglycerides; United States; Update; Urine; Woman; base; diabetes risk; fasting plasma glucose; follow-up; high risk; improved; insight; insulin sensitivity; modifiable risk; novel; novel therapeutics; prevent; prospective; public health relevance; receptor; response; urinary

DESCRIPTION (provided by applicant): 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 application 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. PUBLIC HEALTH RELEVANCE: We propose to conduct the first prospective studies of the impact of acid-base status on the risk of hypertension and diabetes. We expect our study to provide novel insights into the development of hypertension and diabetes and to suggest new strategies, such as alkali therapy, to prevent these diseases. .

描述（由申请人提供）：最近的数据表明，酸碱状态的小变化可能在高血压和2型糖尿病的发展中起重要作用。较低的pH值可能通过促进肾脏盐的保留而导致较高的血压，并通过抑制胰岛素与其受体结合而导致胰岛素抵抗。在国家健康和营养检查调查的健康参与者中，患有血压，禁食葡萄糖和碳酸盐盐的血压被认为是正常的，碳酸氢盐较低与较高的血压和更大的胰岛素抵抗性有关，与身体大小和肾功能无关。由于碳酸氢盐是细胞外液中的主要缓冲液，因此碳酸氢盐下等离子体通常反映出较低的细胞外pH值。作为对酸性产生的补偿性反应的一部分，肾脏减少了尿液中柠檬酸盐的量 - 我们先前在护士健康研究（NHS）参与者中报道了较低的24小时柠檬酸尿液尿液。高碱饮食（例如仪表板饮食）降低了血压，观察性研究报告说，较高的饮食钾（碱摄入量的标志）与糖尿病风险较低有关。由于先前研究了酸碱状态，高血压和糖尿病之间关系的人类研究是横断面的，因此尚不清楚低度代谢酸中毒是这些疾病的原因还是结果。 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）对没有糖尿病的女性血浆碳酸氢盐与胰岛素抵抗变化之间关联的队列研究（n = 750），以及4）嵌套的病例对照研究研究了血浆碳酸氢盐与入口糖尿病风险之间的关系（n = 1500）。该应用代表了研究酸碱状况对患高血压，胰岛素抵抗和2型糖尿病风险的影响的第一个大规模的前瞻性努力。本应用程序的独特优势包括1）长时间前瞻性地累积的更新，详细的暴露信息，2）存档的等离子体和3）大型样本量提供高统计功率。公共卫生相关性：我们建议对酸碱状况对高血压和糖尿病风险的影响进行首次前瞻性研究。我们希望我们的研究能够对高血压和糖尿病的发展提供新的见解，并提出新的策略，例如碱疗法，以防止这些疾病。 。