Dietary carbohydrate effects on GERD in obese Veterans:nutritional or hormonal?

膳食碳水化合物对肥胖退伍军人胃食管反流病的影响：营养还是激素？

• 批准号: 9337248
• 负责人: KEVIN D NISWENDER
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337248
• 关键词: 21 year old; Acids; Address; Adenocarcinoma; Adult; African American; Alcohols; American; Body Weight decreased; Body mass index; Caffeine; Carbohydrates; Chocolate; Chronic; Clinical Data; Comorbidity; Complex; Data; Diagnosis; Diagnostic; Diet; Dietary Carbohydrates; Dietary Factors; Dietary Fiber; Dietary Intervention; Dietary intake; Dyspepsia; Endoscopy; Epidemic; Esophageal; Esophagitis; Fat-Restricted Diet; Fatty acid glycerol esters; Food; Frequencies; Gastric Acid; Gastrins; Gastroenterology; Gastroesophageal reflux disease; Gastrointestinal Diseases; Gastrointestinal Hormones; Genus Mentha; Glucagon; Guidelines; Heartburn; High Fat Diet; Histamine-2 Receptor Antagonist; Hormonal; Inferior esophageal sphincter structure; Inpatients; Insulin; Intake; Investigation; Measures; Mediating; Nutritional; Obesity; Odds Ratio; Outpatients; Overweight; Patients; Pharmaceutical Preparations; Physiological; Prevalence; Proton Pump Inhibitors; Quality of life; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Reflux; Reporting; Resolution; Risk; Risk Factors; Stomach; Symptoms; System; Testing; Time; Total Sugar; Veterans; Visit; Weight; Woman; caucasian American; cell motility; cohort; cost; epidemiologic data; experience; gastrointestinal disorder diagnosis; ghrelin; glucagon-like peptide 1; improved; insulin sensitivity; men; novel; primary outcome; public health relevance; response; saturated fat; sugar

DESCRIPTION (provided by applicant): Gastroesophageal reflux disease (GERD) is highly prevalent in Veterans and the VA spends >$177 million yearly on outpatient prescriptions for GERD. GERD decreases the quality of life and increases the risk for other co-morbidities, and increases the likelihood that a Veteran will undergo costly diagnostic endoscopy. Obesity is associated with significantly increased risk for GERD and Veteran are disproportionately overweight and obese. Thus, the American Gastroenterology Association guidelines advise weight loss for overweight/obese people with GERD. It has long been thought that several dietary factors (acidic foods, spicy foods, mint, chocolate, caffeine and alcohol) as well as high-fat diet may precipitate GERD symptoms - none of which have borne out to close scrutiny. Much of the investigation on dietary factors has targeted total and saturated fat intake as risk factors. When data are adjusted for BMI the relationships between total or saturated fat intake and GERD are not significant. We hypothesize that a specific dietary intervention focused on carbohydrate intake will have significant efficacy to address GERD. We recently conducted a nutrition intervention utilizing a low-carbohydrate / high-fat diet in adults with Class I obesity (BMI 30.0-39.9). At baseline, 25% of subjects reported experiencing GERD symptoms (heartburn, reflux and/or indigestion) at least once a week. Over 1/3 used a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) at least once a week. At baseline, we found that subjects with GERD had significantly higher total sugar intakes (101.6 +/--50.3 vs 82.5 +/- 40.9 grams/day, p = 0.024), but not higher total fat intakes. Notably, total sugar intake was a strong predictor of having GERD symptoms (p = 0.007). Most unexpectedly, all GERD symptoms and medication use had resolved by completion of the 9-week low carbohydrate / high fat diet intervention. Moreover, reduced total sugar intake was significantly associated with improved insulin sensitivity (HOMA-IR score: r =0.37, p =0.001), independent of weight loss. In this proposal we will capitalize on these novel findings and test our overarching hypothesis that the type and/or amount of dietary carbohydrate intake contributes to GERD symptoms in obese people. Specific Hypothesis: Our preliminary findings suggest a physiological mechanism between dietary intake and GERD that may be related to type of dietary carbohydrate intake (complex vs simple carbohydrate). We hypothesize that modifying the type of dietary carbohydrate consumed - by reducing the proportion of simple carbohydrate (sugars) consumed - will reduce or resolve GERD symptoms and medication use in obese Veterans with chronic GERD. We further hypothesize that the mechanistic effects of reducing simple carbohydrate intake is related to either: a) improved dietary fiber intake and/or glycemic load, and thus, reduced amount and duration of esophageal acid exposure; and/or b) improved insulin sensitivity which would positively influence the function of key gastrointestinal hormones that regulate gastric motility and/or lower esophageal sphincter function. Aim 1: To determine effects of dietary carbohydrate consumed (amount and type) on percent time with esophageal pH < 4.0, number of reflux episodes, GERD symptoms and GERD medication use in 200 obese Veterans who have chronic high frequency of GERD symptoms. Aim 2: To assess associations between GERD resolution variables and factors related to potential mechanisms by which modifying dietary carbohydrate intake would resolve/reduce GERD in obese Veterans.

描述（由申请人提供）： 胃食管反流病 (GERD) 在退伍军人中非常普遍，退伍军人管理局每年在 GERD 门诊处方上花费超过 1.77 亿美元。胃食管反流病会降低生活质量，增加其他合并症的风险，并增加退伍军人接受昂贵的诊断内窥镜检查的可能性。肥胖与胃食管反流病的风险显着增加有关，退伍军人超重和肥胖的比例不成比例。因此，美国胃肠病学协会指南建议超重/肥胖的胃食管反流病患者减肥。 长期以来，人们一直认为多种饮食因素（酸性食物、辛辣食物、薄荷、巧克力、咖啡因和酒精）以及高脂肪饮食可能会引发胃食管反流病症状，但这些因素都没有经过严格审查。许多关于饮食因素的调查都将总脂肪和饱和脂肪摄入量作为危险因素。当根据 BMI 调整数据后，总脂肪或饱和脂肪摄入量与 GERD 之间的关系并不显着。我们假设，针对碳水化合物摄入的特定饮食干预将对解决胃食管反流病具有显着功效。 我们最近利用低碳水化合物/高脂肪饮食对 I 级肥胖成人（BMI 30.0-39.9）进行了营养干预。在基线时，25% 的受试者报告每周至少出现一次 GERD 症状（胃灼热、反流和/或消化不良）。超过 1/3 的人每周至少使用一次质子泵抑制剂 (PPI) 或组胺 2 受体拮抗剂 (H2RA)。在基线时，我们发现患有 GERD 的受试者的总糖摄入量显着较高（101.6 +/--50.3 vs 82.5 +/- 40.9 克/天，p = 0.024），但总脂肪摄入量并不更高。值得注意的是，总糖摄入量是 GERD 症状的有力预测因子 (p = 0.007)。最出乎意料的是，在完成 9 周的低碳水化合物/高脂肪饮食干预后，所有 GERD 症状和药物使用均得到解决。此外，总糖摄入量的减少与胰岛素敏感性的改善显着相关（HOMA-IR评分：r = 0.37，p = 0.001），与体重减轻无关。在本提案中，我们将利用这些新发现并测试我们的总体假设，即膳食碳水化合物摄入的类型和/或数量会导致肥胖人群的胃食管反流病症状。 具体假设：我们的初步研究结果表明饮食摄入和胃食管反流病之间的生理机制可能与饮食碳水化合物摄入类型（复杂碳水化合物与简单碳水化合物）有关。我们假设，通过减少消耗的简单碳水化合物（糖）的比例来改变膳食碳水化合物的类型，将减少或解决患有慢性胃食管反流病的肥胖退伍军人的胃食管反流病症状和药物使用。我们进一步假设减少简单碳水化合物摄入量的机制效应与以下任一相关：a）改善膳食纤维摄入量和/或血糖负荷，从而减少食道酸暴露的量和持续时间；和/或 b) 改善胰岛素敏感性，这将对调节胃动力和/或下食管括约肌功能的关键胃肠激素的功能产生积极影响。目标 1：确定膳食碳水化合物消耗（数量和类型）对 200 名患有慢性高频率 GERD 症状的肥胖退伍军人的食管 pH < 4.0 时间百分比、反流发作次数、GERD 症状和 GERD 药物使用的影响。目标 2：评估 GERD 解决变量与潜在机制相关因素之间的关联，通过改变膳食碳水化合物摄入量可以解决/减少肥胖退伍军人的 GERD。