Effects of Intermittent Fasting on Glycemic Control in Patients with Diabetes

间歇性禁食（IF）是每日热量限制的替代方案，用于产生临床相关的体重减轻。 虽然间歇性禁食相对于每日热量限制并不增加体重减轻，但修改 通过间歇性能量限制（IER）或时间限制进食（TRE）的食物摄入时间， 间歇性禁食可以为血糖控制提供明显的益处。然而，这两种IF方法 尚未在2型糖尿病（T2 D）患者中进行全面测试或比较。此外，胰腺β 对混合餐的细胞反应性和胰岛素作用依赖于功能正常的肠促胰岛素 轴线两种促胰岛素肽，葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样多肽（Glucagon-like）， 肽-1（GLP-1）对于餐后血糖控制是必需的。肠促胰岛素刺激的胰岛素作用有助于 在健康成年人中，超过70%的胰岛素对膳食的反应，使单独的葡萄糖的作用黯然失色。 刺激胰岛素分泌。在2型糖尿病患者中，肠促胰岛素反应迟钝，导致 血糖控制较差。类似地，较高水平的炎症减弱胰岛素敏感性。间歇性禁食 在小鼠中减少炎症并改善肠促胰岛素表达，然而这些作用还有待于进一步研究。 在T2 D患者中复制。我们的目标是评估两种IF方法的潜在获益机制 2型糖尿病患者的血糖控制。主要目的是确定两种形式的 间歇性禁食对胰岛素作用和全身胰岛素敏感性的影响。我们还将比较身体的变化 IER和TRE之间的组合，并进行第一次试验，以确定两种间歇性 禁食方法对肠促胰岛素反应的影响。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反应的潜在预测因素。我们将 通过利用和补充现有的使用两种IF方法的随机对照试验来做到这一点 在6个月的多成分生活方式改变计划中， 通过远程提供的每两周一次的小组会议，为糖尿病患者提供治疗方案。主要终点将在 第0、12、26和52周。除了已经收集的体重变化数据外， 通过HbA 1c和动态血糖监测控制，我们将进行3小时9分混合餐耐受性 用葡萄糖、胰岛素和c肽进行MMTT试验，以估计胰岛素分泌和胰腺β 细胞功能此外，我们还将评估IER和TRE对身体成分、肠促胰岛素反应 和炎症细胞因子水平。重复测量混合模型 分析将用于评估每种方法对结局指标的影响，其次， 比较一下这两种形式的IF。我们研究的长期目标是确定间歇性禁食是否 这些方法是糖尿病治疗标准护理的有效替代方案。其次，我们的目标是 确定哪些患者最有可能从间歇性禁食方案中获益。

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.