Grant: CIHR Fellowship

Type 2 diabetes (T2D) has a significant impact on brain health, including loss of brain tissue and impaired cognitive functions such as memory. People with T2D are up to 100% more likely to develop Alzheimer's disease (AD) and 200% more likely to develop dementia. In fact, AD has been called 'type 3 diabetes' given that it shares the same root cause as T2D - impaired ability of neurons to uptake and use glucose for fuel (metabolic dysfunction). This is problematic because the brain relies almost exclusively on glucose for fuel, explaining why the brain is so vulnerable to T2D. Despite this knowledge, drug interventions are largely ineffective, highlighting the need for innovative approaches. An intriguing therapeutic approach that holds potential for improving brain health in individuals with T2D is the ingestion of ketone body (KB) supplements. Ingestion of ketone supplements increases circulating KB levels in the blood and subsequently increases the utilization of KB as fuel by the brain. Interestingly, the use of KB for fuel is not impaired by diseases such as AD and T2D, and work in animals show that it creates positive adaptions that may protect against neurological disease and improve brain function. However, high-quality research trials examining the effect of KB ingestion on brain function in humans with T2D have yet to be performed. This study will investigate the effect of acute (one dose) and short-term (14 days) KB supplementation on measures of brain function in individuals with T2D in order to characterize the mechanisms by which KB affect the brain and to evaluate their effectiveness as a therapy for individuals with T2D. For the first time in humans, using a high-quality research design, the effects of KB ingestion on brain function will be established. These results will help us understand how the brain uses KB for fuel and may have important implications for therapeutic approaches to combat T2D-related cognitive impairment.