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

在过去的10年里，英国被诊断患有2型糖尿病（T2 D）的人数增加了一倍多，每天约有700人被新诊断出来。预防和/或逆转T2 D是全球和NHS医疗保健的优先事项。非常低热量和/或低碳水化合物饮食可能有效，但通常需要强化干预和/或持续的行为支持。因此，研究额外的饮食治疗策略是明确必要的。患有T2 D的人在一天的大部分时间内血糖（葡萄糖）水平高于正常范围，这导致许多与该疾病相关的心血管并发症。血糖升高的原因很复杂，但通常是由于体内葡萄糖产生增加和身体葡萄糖使用减少。我们可以使用特殊标记的葡萄糖（“稳定同位素示踪剂”）在T2 D患者中进行实验，以精确测量身体如何产生和使用葡萄糖。这些实验表明，T2 D患者在空腹时（例如过夜和早餐前）葡萄糖产生增加，而餐后（例如早餐，午餐和晚餐后）葡萄糖使用减少。我们的研究表明，一种名为酮单酯（KME）的新“补充饮料”可以增加我们血液中的酮水平。当我们不吃东西或长时间节食时，我们的身体会自然产生酮，这可能是低卡路里和低碳水化合物（“酮”）饮食起作用的原因之一。我们的研究还表明，KME饮料可以降低T2 D患者餐后血糖水平高达30%。我们不知道KME饮料如何降低血糖水平，但我们认为这可能是由于阻止身体将脂肪释放到血液中，这往往会增加葡萄糖的产生并减少葡萄糖的使用。 该项目的目的是在T2 D患者中进行一项双盲，随机，安慰剂对照试验，其中葡萄糖“稳定同位素示踪剂”将用于精确测量葡萄糖的产生和使用，以应对餐前KME饮料。我们还将评估这是否是由于降低血脂水平，是否有任何影响持续多餐，重要的是，这些影响是否与参与者“燃烧”的卡路里增加有关。这些发现将为更大规模的临床试验铺平道路，以评估KME摄入作为T2 D治疗选择的有效性，并有助于确定和开发T2 D的其他营养或药物治疗。

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.