Investigating the blood glucose lowering effect of exogenous ketone ingestion in people with type 2 diabetes

研究外源性酮摄入对 2 型糖尿病患者的降血糖作用

• 批准号: MR/Y008804/1
• 负责人: Francis Stephens
• 金额: $ 46.43万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY008804%2F1
• 关键词: Investigating; blood; glucose; lowering; effect

The number of people diagnosed with type 2 diabetes (T2D) has more than doubled over the last 10 years in the UK, with around 700 people newly diagnosed every day. Prevention and/or reversal of T2D is a global and NHS health care priority. Very low-calorie and/or low-carbohydrate diets can be efficacious but typically require intensive intervention and/or ongoing behavioural support. Thus, investigation of additional dietary treatment strategies is clearly warranted. People with T2D have elevated blood sugar (glucose) levels above the normal range for most of the day, which leads to many of the cardiovascular complications associated with the disease. The reasons for increased blood glucose are complex but are generally due to increased glucose production in the body and reduced glucose use by the body. We can perform experiments in people with T2D using specially labelled glucose ("stable isotope tracers") to measure precisely how the body produces and uses glucose. These experiments show that increased glucose production occurs in people with T2D when they are fasting (e.g. overnight and before breakfast), whereas reduced glucose use are seen following a meal (e.g. after breakfast, lunch and dinner). Our research has shown that a new "supplement drink" call a ketone monoester (KME) can increase levels of ketones in our blood. Ketones are produced naturally by our body when we don't eat or if we diet for a long period of time, and might be one reason why very low-carlorie and low-carbohydrate ("keto") diets work. Our research also demonstrated that a KME drink can lower blood glucose levels by up to 30% after a meal in people who have T2D. We do not know how the KME drink lowered blood glucose levels by such a remarkable amount but we think it might be due to stopping the body from releasing fat into the blood, which tends to increase glucose production and decrease glucose use. The aim of this project is to perform a double-blind, randomised, placebo-controlled trial in people with T2D where glucose "stable isotope tracers" will be used to precisely measure glucose production and use in response to a KME drink before a meal. We will also assess whether this was due to lowering blood fat levels, if any effects persist over multiple meals and, importantly, whether the effects are associated with an increase in how many calories the participants "burn". These findings will pave the way for larger clinical trials to assess the efficacy of KME ingestion as a treatment option for T2D and could help identify and development other nutritional or drug treatments for T2D.

在过去的10年中，被诊断为2型糖尿病（T2D）的人数增加了一倍以上，每天大约有700人新诊断。 T2D的预防和/或逆转是全球和NHS医疗保健优先事项。非常低热量和/或低碳水化合物饮食可以有效，但通常需要进行强化干预和/或持续的行为支持。因此，明确保证对其他饮食治疗策略进行调查。在一天中的大部分时间里，T2D患者的血糖水平升高（葡萄糖）水平升高，这导致许多与该疾病相关的心血管并发症。血糖增加的原因很复杂，但通常是由于体内葡萄糖产生增加以及人体使用减少的葡萄糖。我们可以使用特殊标记的葡萄糖（“稳定的同位素示踪剂”）对患有T2D的人进行实验，以精确测量人体如何产生和使用葡萄糖。这些实验表明，在禁食时，T2D的人会发生增加的葡萄糖产生（例如，隔夜和早餐前），而在一顿饭后会看到葡萄糖减少（例如早餐，午餐和晚餐后）。我们的研究表明，一种新的“补充饮料”称为酮单酯（KME）可以增加血液中酮的水平。当我们不进食或长时间节食时，我们的身体会自然产生酮，这可​​能是为什么非常低碳酸盐和低碳水化合物（“酮”）饮食的原因之一。我们的研究还表明，在患有T2D的人中，一顿KME饮料可以降低血糖水平多达30％。我们不知道KME饮料如何通过如此出色的量降低血糖水平，但我们认为这可能是由于阻止人将脂肪释放到血液中，这倾向于增加葡萄糖产生并减少葡萄糖的使用。 该项目的目的是在患有T2D的人中进行双盲，随机，安慰剂对照试验，其中葡萄糖“稳定的同位素示踪剂”将用于精确测量葡萄糖的产生和用餐前的葡萄糖产生和使用。我们还将评估这是否是由于降低血脂水平，如果有多餐的任何影响持续存在，重要的是，这些影响是否与参与者“燃烧”的卡路里增加了多少卡路里有关。这些发现将为大型临床试验评估KME摄入作为T2D的治疗选择的功效铺平道路，并可以帮助识别和开发其他T2D的其他营养或药物治疗。