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

描述(由申请人提供)： 胃食道反流病(GERD)在退伍军人中非常普遍，退伍军人管理局每年花费1.77亿美元用于GERD的门诊处方。GERD降低了生活质量，增加了其他并发症的风险，并增加了退伍军人接受昂贵的诊断性内窥镜检查的可能性。肥胖与GERD的风险显著增加有关，退伍军人超重和肥胖的比例不成比例。因此，美国胃肠病协会的指南建议超重/肥胖的GERD患者减肥。长期以来，人们一直认为几种饮食因素(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导致GERD症状--这些都没有经过仔细的审查。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。当对BMI数据进行调整时，总或饱和脂肪摄入量与GERD之间的关系并不显着。我们假设，以碳水化合物摄入为重点的特定饮食干预将对解决GERD具有显著效果。我们最近对I类肥胖(BMI 30.0-39.9)的成年人进行了一项营养干预，采用低碳水化合物/高脂肪饮食。在基线时，25%的受试者报告每周至少经历一次GERD症状(胃灼热、反流和/或消化不良)。超过1/3的患者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，我们发现胃肠道反流病患者的总糖摄入量明显更高(101.6 +/--50.3vs82.5+/-40.9g/天，p=0.024)，但没有更高的总脂肪摄入量。值得注意的是，总糖摄入量是出现胃肠道反流病症状的有力预测因素(p=0.007)。最出人意料的是，所有GERD症状和药物使用在完成9周的低碳水化合物/高脂肪饮食干预后都得到了缓解。此外，总糖摄入量的减少与胰岛素敏感性的改善显著相关(HOMA-IR评分：r=0.37，p=0.001)，与体重减轻无关。在这项建议中，我们将利用这些新的发现，并测试我们的总体假设，即饮食碳水化合物摄入量的类型和/或数量与肥胖者的GERD症状有关。具体假设：我们的初步发现表明饮食摄入量和GERD之间存在一种生理机制，这可能与饮食碳水化合物摄入量的类型(复杂碳水化合物与单一碳水化合物)有关。我们假设，改变饮食碳水化合物的类型--通过减少单一碳水化合物(糖)的消耗比例--将减少或解决患有慢性GERD的肥胖退伍军人的GERD症状和药物使用。我们进一步假设，减少单纯碳水化合物摄入量的机制效应与以下两方面有关：a)改善膳食纤维摄入量和/或血糖负荷，从而减少食管酸暴露的数量和持续时间；和/或b)改善胰岛素敏感性，这将积极影响调节胃动力和/或下食道括约肌功能的关键胃肠激素的功能。目的：探讨膳食碳水化合物摄入量(量和类型)对200例慢性高发肥胖退伍军人的食道pH值为4.0的百分比时间、反流次数、GERD症状和GERD药物使用的影响。目的2：评估GERD解决变量与改变膳食碳水化合物摄入量以解决/减少肥胖退伍军人GERD的潜在机制相关因素之间的关系。

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.