Pharmacokinetics and Subjective Responses to Alcohol After Bariatric Surgery

减肥手术后的药代动力学和对酒精的主观反应

• 批准号: 9901408
• 负责人: MARTA YANINA PEPINO DE GRUEV
• 金额: $ 31.22万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-24 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901408
• 关键词: Affect; Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcoholism; Alcohols; American; Anti-Anxiety Agents; Beverages; Blood alcohol level measurement; Body Weight; Brain; Clinical Practice Guideline; Closure by clamp; Consumption; Control Groups; Counseling; Data; Development; Dose; Drug Kinetics; Ensure; Euphoria; Excision; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Family history of; Fatty acid glycerol esters; Feeling; Food; Foundations; Gas Chromatography; Gastrectomy; Gastric Bypass; Goals; Health Benefit; Ingestion; Intestines; Intravenous; Laparoscopy; Longitudinal Studies; Mediating; Monitor; Obesity; Obesity Epidemic; Operative Surgical Procedures; Oral; Patients; Peptides; Pharmaceutical Preparations; Placebos; Play; Procedures; Process; Questionnaires; Randomized; Recording of previous events; Research; Research Design; Rewards; Risk; Rodent Model; Role; Schedule; Stomach; Testing; Time; United States; Woman; absorption; addiction; alcohol effect; alcohol misuse prevention; alcohol response; alcohol reward; alcohol risk; alcohol sensitivity; alcohol testing; alcohol use disorder; bariatric surgery; brain pathway; drug reward; evidence base; ghrelin; glucagon-like peptide 1; high risk; non-alcoholic; obesity treatment; public health relevance; response

 DESCRIPTION (provided by applicant): More than one million Americans have undergone bariatric surgery over the last decade and, given the obesity epidemic, it is anticipated that this number will continue to rise. Bariatric surgery procedures (including Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG], and the purely restrictive laparoscopic adjustable gastric banding [LAGB] procedure) provide the most successful long-term treatment for obesity. However, there is an increased risk of alcohol use disorders (AUD) after surgeries that remove part of the stomach. The precise mechanism(s) underlying this association is uncertain but we hypothesize is due to gastric resection surgery-induced changes in both 1) alcohol pharmacokinetics and 2) gut-brain peptides that play a role in food- and drug-induced reward (e.g., ghrelin, glucagon-like peptide-1 (GLP-1)). Changes in both alcohol pharmacokinetics and central sensitivity to reward could affect how people feel after they drink alcohol (i.e., subjectie responses to alcohol) and increase their risk of developing an AUD. However, to date the effect of surgery-induced changes on subjective responses to alcohol within the same subject before and after surgery using validated questionnaires has not been determined, and it is unknown whether some surgery-induced changes in alcohol's subjective effects are centrally mediated, that is independent of changes in alcohol absorption, as recently shown in a rodent model of RYGB. Therefore, the primary aims of this proposed longitudinal study are to determine the effects of RYGB, SG, and LAGB on i) alcohol's pharmacokinetics (Aim 1) and ii) subjective responses to alcohol after alcohol is ingested (Aim 2), or intravenously clamped at identical BAC among groups (Aim 3). We will use the clamp approach to control for surgery-induced changes in alcohol absorption and validated questionnaires to assess changes in subjective responses to alcohol known to be associated with increased risk of developing AUD. As a secondary, exploratory, aim, we will determine the effects of RYGB, SG, and LAGB on gut peptide release (e.g. ghrelin, GLP-1) after alcohol is consumed and explore relationships between changes in peptide concentrations and subjective responses to alcohol. We hypothesize that RYGB and SG, but not LAGB, will 1) accelerate alcohol absorption, such that peak BAC will be reached faster and will be higher after than before surgery, and 2) increase sensitivity to positive subjective effects of alcohol even when alcohol is clamped such that all groups have equivalent brain BACs. This project will answer the question of whether SG and RYGB affect alcohol pharmacokinetics, and whether in addition they increase sensitivity to rewarding effects of alcohol independently of changes in alcohol absorption. This information could influence clinical practice guidelines for patients, both in the choice of bariatric surgery for specific high risk people (e.g. personal or family history of addiction) and appropriate counselling and monitoring postsurgery. In addition, our findings may further implicate the role of gut peptides in alcohol reward, potentially leading to the study of new treatment approaches for AUD.

 描述（由适用提供）：在过去的十年中，超过一百万的美国人接受了减肥手术，鉴于肥胖症的流行，预计这是 数字将继续上升。减肥手术程序（包括Roux-en-Y胃旁路[RYGB]和袖子胃[SG]，以及纯粹的限制性腹腔镜可调式胃带[LAGB程序）为肥胖提供了最成功的长期治疗。但是，在手术后，饮酒障碍（AUD）的风险增加了。这种关联的基础机制尚不确定，但我们假设是由于胃切除手术诱导的诱导的变化1）酒精药物药物药物和2）肠脑肽在食品和药物诱导的奖励中起着作用（例如，ghrelin，ghrelin，ghrelin，葡萄糖，葡萄糖型peptide-1（glpp-1））。酒精药代动力学和对奖励的中心敏感性的变化可能会影响人们喝酒后的感受（即主题对酒精的反应），并增加了他们开发AUD的风险。然而，迄今为止，尚未确定手术诱导的变化对使用经过验证的问卷进行手术前后对酒精的主观反应的影响，尚不确定某些手术诱导的酒精主观效应的某些手术诱导的饮酒主观效应的变化是否与Rygb的Ryent rygb模型相同，这与酒精滥用的变化无关。因此，该提案纵向研究的主要目的是确定RYGB，SG和LAGB对I）i）酒精药代动力学（AIM 1）和II）对酒精后对酒精的主观反应（AIM 2），或在相同的BAC中静脉夹住酒精（AIM 2）或静脉内夹住BAC（AIM 3）。我们将使用夹具方法来控制手术诱导的酒精抽象变化和经过验证的问卷，以评估已知对酒精的主观反应的变化，该反应与增加AUD的风险增加有关。作为次要的，探索性的目标，我们将确定RYGB，SG和LAGB对酒精消耗之后的肠肽释放（例如Ghrelin，GLP-1）的影响，并探索肽浓度的变化与酒精的主观反应之间的关系。我们假设RYGB和SG而不是LAGB，1）会加速酒精的吸收，使得BAC的达到峰值的峰值将更快地达到峰值，并且在手术前会更高，并且2）2）即使在所有基团夹住酒精时，也会提高对酒精阳性主观影响的敏感性，以使所有基团具有相等的BAC。该项目将回答有关SG和RYGB是否影响酒精药代动力学的问题，以及它们是否增加了对酒精对酒精滥用变化的奖励影响的敏感性。这些信息可能会影响患者的临床实践指南，无论是选择针对特定高风险人（例如，成瘾的个人或家族史）的减肥手术以及适当的咨询和监测术后手术。此外，我们的发现可能进一步暗示肠辣椒在酒精奖励中的作用，这可能导致研究了新的AUD治疗方法。