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）： 胃食管反流疾病（GERD）在退伍军人中非常普遍，VA每年在GERD的门诊处方上花费> 1.77亿美元。 GERD降低了生活质量并增加了其他合并症的风险，并增加了退伍军人经历昂贵的诊断内窥镜检查的可能性。肥胖与GERD的风险显着增加有关，而退伍军人则超重和肥胖。因此，《美国胃肠病学协会指南》为超重/肥胖者的体重减轻提供了建议。 长期以来，人们一直认为，几种饮食因素（酸性食品，辛辣食物，薄荷，巧克力，咖啡因和酒精）以及高脂饮食可能会促成GERD症状 - 这些饮食症状都没有经历。对饮食因素的大部分研究都针对总脂肪作为风险因素。当对BMI调整数据时，总脂肪摄入和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措施将具有明显的疗效来解决GERD。 最近，我们利用I级肥胖症成人的低碳水化合物 /高脂饮食进行了营养干预（BMI 30.0-39.9）。在基线时，有25％的受试者每周至少一次患有GERD症状（胃灼热，反流和/或消化不良）。超过1/3使用质子泵抑制剂（PPI）或组胺2受体拮抗剂（H2RA）至少每周一次。在基线时，我们发现患有GERD的受试者的总糖摄入量明显更高（101.6 +/ - 50.3 vs 82.5 +/- 40.9克/天，p = 0.024），但总脂肪摄入量不高。值得注意的是，总糖摄入量是具有GERD症状的有力预测指标（P = 0.007）。最出乎意料的是，通过完成9周的低碳水化合物 /高脂肪饮食干预，所有GERD症状和药物使用都已解决。此外，总糖摄入量减少与改善胰岛素敏感性显着相关（HOMA-IR评分：R = 0.37，P = 0.001），与体重减轻无关。在此提案中，我们将利用这些新颖的发现，并检验我们的总体假设，即饮食中碳水化合物摄入的类型和/或数量会导致肥胖者的GERD症状。 具体假设：我们的初步发现表明，饮食摄入和GERD之间的生理机制可能与饮食中碳水化合物摄入的类型有关（复杂的碳水化合物与简单的碳水化合物）。我们假设修改消耗的饮食碳水化合物的类型 - 通过减少消耗的简单碳水化合物（糖）的比例 - 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，减少简单的碳水化合物摄入的机械作用与以下方面有关：a）改善饮食纤维摄入和/或血糖负荷，从而减少食管酸暴露的量和持续时间；和/或b）提高胰岛素敏感性，这将积极影响调节胃运动和/或较低食管括约肌功能的关键胃肠道激素的功能。目的1：确定食管pH <4.​​0的饮食碳水化合物（数量和类型）的影响（数量和类型），回流发作的数量，GERD症状和GERD用药在200名患有慢性GERD症状的肥胖退伍军人中。目的2：评估GERD分辨率变量与与潜在机制相关的因素之间的关联，这些机制修改饮食碳水化合物的摄入量可以解决/减少肥胖退伍军人的GERD。