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

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，VA每年花费超过1.77亿美元用于GERD的门诊处方。GERD降低生活质量，增加其他并发症的风险，并增加退伍军人接受昂贵的诊断内镜检查的可能性。肥胖与胃食管反流病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，美国胃肠病学协会指南建议超重/肥胖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-其中没有一种经过仔细审查。许多关于饮食因素的研究都将总脂肪和饱和脂肪摄入量作为风险因素。当调整BMI数据时，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，一个特定的饮食干预，重点是碳水化合物的摄入量将有显着的疗效，以解决胃食管反流病。 我们最近对I类肥胖症（BMI 30.0-39.9）成人进行了一项营养干预，采用低碳水化合物/高脂肪饮食。基线时，25%的受试者报告每周至少发生一次GERD症状（烧心、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（H2 RA）。在基线时，我们发现GERD受试者的总糖摄入量显著较高（101.6 +/-50.3 vs 82.5 +/- 40.9克/天，p = 0.024），但总脂肪摄入量并没有增加。值得注意的是，总糖摄入量是GERD症状的强预测因子（p = 0.007）。最出乎意料的是，所有GERD症状和药物使用均在9周低碳水化合物/高脂肪饮食干预完成时消退。此外，总糖摄入量减少与胰岛素敏感性改善显著相关（HOMA-IR评分：r =0.37，p =0.001），与体重减轻无关。在这项提案中，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的类型和/或数量有助于肥胖人群的GERD症状。 具体假设：我们的初步研究结果表明，饮食摄入和GERD之间的生理机制可能与饮食碳水化合物摄入的类型（复合碳水化合物与简单碳水化合物）有关。我们假设，通过减少简单碳水化合物（糖）消耗的比例来改变饮食碳水化合物消耗的类型，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，减少简单碳水化合物摄入的机制效应与以下任一者有关：a）改善膳食纤维摄入和/或血糖负荷，从而减少食管酸暴露的量和持续时间;和/或B）改善胰岛素敏感性，这将积极影响调节胃运动和/或下食管括约肌功能的关键胃肠激素的功能。目标1：在200名患有慢性高频率GERD症状的肥胖退伍军人中，确定饮食碳水化合物消耗（量和类型）对食管pH < 4.0的时间百分比、反流发作次数、GERD症状和GERD药物使用的影响。目标二：评估GERD缓解变量与潜在机制相关因素之间的相关性，通过该机制调整饮食碳水化合物摄入量可缓解/减少肥胖退伍军人的GERD。

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.