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

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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.