Effects of Intermittent Fasting on Glycemic Control in Patients with Diabetes

间歇性禁食对糖尿病患者血糖控制的影响

• 批准号: 10856717
• 负责人: Felicia Steger
• 金额: $ 23.5万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10856717
• 关键词: Adult; Body Composition; Body Weight Changes; Body Weight decreased; C-Peptide; Caloric Restriction; Cell physiology; Continuous Glucose Monitor; Data; Diabetes Mellitus; Eating; Gastric Inhibitory Polypeptide; Glucose; Glycosylated hemoglobin A; Goals; Group Meetings; Health education; Hour; Individual; Inflammation; Inflammatory Response Pathway; Insulin; Intermittent fasting; Intervention; Kansas; Life Style; Measures; Metabolic; Metabolism; Modeling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome Measure; Patients; Phenotype; Randomized, Controlled Trials; Regimen; Research; Structure of beta Cell of islet; Testing; Time-restricted feeding; blood glucose regulation; clinically relevant; gastric inhibitory polypeptide receptor; glucagon-like peptide 1; glycemic control; improved; insulin secretion; insulin sensitivity; predicting response; primary endpoint; programs; remote delivery; response; standard of care; Adult; Body Composition; Body Weight Changes; Body Weight decreased; C-Peptide; Caloric Restriction; Cell physiology; Continuous Glucose Monitor; Data; Diabetes Mellitus; Eating; Gastric Inhibitory Polypeptide; Glucose; Glycosylated hemoglobin A; Goals; Group Meetings; Health education; Hour; Individual; Inflammation; Inflammatory Response Pathway; Insulin; Intermittent fasting; Intervention; Kansas; Life Style; Measures; Metabolic; Metabolism; Modeling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome Measure; Patients; Phenotype; Randomized, Controlled Trials; Regimen; Research; Structure of beta Cell of islet; Testing; Time-restricted feeding; blood glucose regulation; clinically relevant; gastric inhibitory polypeptide receptor; glucagon-like peptide 1; glycemic control; improved; insulin secretion; insulin sensitivity; predicting response; primary endpoint; programs; remote delivery; response; standard of care

Intermittent fasting (IF) is an alternative to daily calorie restriction for producing clinically relevant weight loss. Though intermittent fasting does not increase weight loss relative to daily calorie restriction, modifying the timing of food intake via intermittent energy restriction (IER) or time-restricted eating (TRE), two forms of intermittent fasting, may provide a pronounced benefit to glycemic control. However, these two IF approaches have not been thoroughly tested or compared in patients with type 2 diabetes (T2D). Further, pancreatic beta cell responsiveness and insulin action in response to a mixed meal depend on a functionally normal incretin axis. Two insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are essential for postprandial glucose control. Incretin-stimulated insulin action contributes more than 70% of the insulin response to a meal in healthy adults, overshadowing the effect of glucose alone to stimulate insulin secretion. In patients with type 2 diabetes, the incretin response is blunted, contributing to poorer glycemic control. Similarly, higher levels of inflammation blunt insulin sensitivity. Intermittent fasting reduces inflammation and improves incretin expression in mice, however these effects have yet to be replicated in patients with T2D. Our goal is to evaluate potential mechanisms of benefit for two IF approaches on glycemic control in patients with T2D. The primary aim is to determine the effects of two forms of intermittent fasting on insulin action and whole-body insulin sensitivity. We will also compare changes in body composition between IER and TRE and conduct the first trial to determine the effects of both intermittent fasting approaches on the incretin response to a meal. In exploratory analyses, we will phenotype individuals based on metabolic assessments to determine potential predictors of response from each intervention. We will do this by leveraging and supplementing an existing randomized controlled trial utilizing both IF approaches within a 6-month multicomponent lifestyle change program incorporating a comprehensive health education program for diabetes via biweekly group meetings delivered remotely. Primary endpoints will be collected at weeks 0, 12, and 26, and 52 weeks. In addition to data already being collected on weight change, glycemic control via HbA1c and continuous glucose monitoring, we will conduct a 3-hour, 9-point mixed meal tolerance test (MMTT) with glucose, insulin, and c-peptide to allow for estimates of insulin secretion and pancreatic beta cell function. Additionally, we will assess the effects of IER and TRE on body composition, incretin response and inflammatory cytokine levels during the 12-month intervention. Mixed models with repeated measures analysis will be used to assess the effect of each approach on outcome measures and, secondarily, to compare these two forms of IF. The long-term goal of our research is to determine whether intermittent fasting approaches are an effective alternative to standard of care for diabetes treatment. Secondarily, our goal is to determine which patients are most likely to benefit from either intermittent fasting regimen.

间歇性禁食（如果）是每天限制临床相关的体重减轻的替代品。 尽管间歇性禁食不会相对于每日卡路里限制增加体重减轻，但修改 食物摄入的时间通过间歇能量限制（IER）或时间限制饮食（TRE），两种形式 间歇性禁食可能为血糖控制提供明显的好处。但是，这两个如果方法 在2型糖尿病（T2D）患者中尚未对其进行彻底测试或比较。此外，胰腺β 响应混合餐的细胞反应能力和胰岛素作用取决于功能正常 轴。两种胰岛素肽，葡萄糖依赖性胰岛素多肽（GIP）和胰高血糖素样 肽-1（GLP-1）对于餐后葡萄糖控制至关重要。肠染料蛋白刺激的胰岛素作用有助于 在健康成年人中，超过70％的胰岛素反应对餐食的反应掩盖了仅葡萄糖的影响 刺激胰岛素分泌。在2型糖尿病的患者中 较差的血糖控制。同样，较高的炎症钝性胰岛素敏感性。间歇性禁食 减少炎症并改善小鼠的肠降血糖素表达，但是这些作用尚未 在T2D患者中复制。我们的目标是评估两个方法的潜在利益机制 T2D患者的血糖控制。主要目的是确定两种形式的影响 间歇性禁食胰岛素作用和全身胰岛素敏感性。我们还将比较身体的变化 IER和TRE之间的组成，并进行了第一个试验，以确定两者间歇性的影响 禁食的肠降凝素反应接近一顿饭。在探索性分析中，我们将表型个体 基于代谢评估，以确定每种干预措施的潜在反应预测指标。我们将 通过利用和补充现有的随机对照试验并使用两种方法来执行此操作 在一个为期6个月的多组分生活方式改变计划中，结合了全面的健康教育 通过双周小组会议的糖尿病计划进行了远程交付。将在 第0、12和26周和52周。除了已经收集了有关体重变化的数据外，血糖 通过HBA1C和连续的葡萄糖监测控制，我们将进行3小时的9分混合餐容差 用葡萄糖，胰岛素和C肽测试（MMTT），以估算胰岛素分泌和胰腺β 细胞功能。此外，我们将评估IER和TRE对身体成分，肠降直直染素反应的影响 在12个月的干预期间和炎症细胞因子水平。重复措施的混合模型 分析将用于评估每种方法对结果度量的影响，其次， 比较这两种形式的if。我们研究的长期目标是确定间歇性禁食 方法是糖尿病治疗标准护理标准的有效替代方法。其次，我们的目标是 确定哪种患者最有可能受益于间歇性禁食方案。