Effects of Intermittent Fasting on Glycemic Control in Patients with Diabetes

间歇性禁食(IF)是一种替代每日卡路里限制的临床减肥方法。 虽然间歇性禁食不会增加相对于每日卡路里限制的体重减轻，但修改 通过间歇性能量限制(IER)或限时进食(Tre)的食物摄入时间，这是两种形式的 间歇性禁食可能对血糖控制有明显的好处。然而，这两个IF方法 尚未在2型糖尿病(T2D)患者中进行彻底测试或比较。此外，胰岛β 细胞反应性和胰岛素对混合餐的反应取决于功能正常的内分泌 轴心。两种胰岛素样多肽，葡萄糖依赖型胰岛素样多肽(GIP)和类胰高血糖素 多肽-1(GLP-1)是餐后血糖控制所必需的。胰岛素刺激的胰岛素作用 在健康成年人中，超过70%的胰岛素对一顿饭的反应，盖过了单独使用葡萄糖的影响 刺激胰岛素分泌。在2型糖尿病患者中，胰岛素反应迟钝，导致 血糖控制较差。同样，较高的炎症水平会削弱胰岛素敏感性。间歇性禁食 减少小鼠的炎症和改善胰岛素的表达，然而这些效果还没有得到证实 在T2D患者中复制。我们的目标是评估两种IF方法的潜在受益机制 T2D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之间的组成，并进行第一次试验，以确定两者间歇性的影响 禁食对一顿饭的胃肠促进素反应。在探索性分析中，我们将对个体进行表型分析 根据新陈代谢评估，确定每次干预反应的潜在预测因素。我们会 通过利用和补充现有的利用两种IF方法的随机对照试验来实现这一点 在为期6个月的多成分生活方式改变计划中纳入全面的健康教育 通过两周一次的小组会议远程提供的糖尿病方案。将在以下位置收集主端点 0周、12周、26周和52周。除了已经收集的关于体重变化的数据外，血糖升高 通过糖化血红蛋白和持续血糖监测进行控制，我们将进行3小时9点混合餐耐量 用葡萄糖、胰岛素和C-肽检测(MMTT)以评估胰岛素分泌和胰岛β细胞功能 细胞功能。此外，我们还将评估IER和Tre对体成分、胰岛素反应的影响。 在12个月的干预期间，炎性细胞因子水平。具有重复测量的混合模型 分析将用于评估每种方法对结果衡量的影响，其次是 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两种间歇性禁食方案中受益。

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.