Grant: CIHR-ICRH Travel Awards - ICRH / Vascular pool

The ketogenic diet (KD) is an extremely carbohydrate restricted diet that has re-emerged for the management of blood sugar. In 2020, Diabetes Canada joined other international organizations in approving its use in the management of type 2 diabetes (T2D) based on short term studies showing weight loss, improved blood sugar control, and reduced need for diabetes medications in people living with T2D. However, the longer-term impact of extreme fat consumption (>70% of calories), restricted carbohydrates (<50 g/day), and fat-produced ketone bodies on T2D and insulin production and release are not known. To assess the impact of KD intervention on obese mice, we fed male and female mice a high fat diet (HFD) for 10 weeks and then mice either maintained the HFD or underwent diet intervention with a KD or our regular mouse diet for 12 weeks. Male mice on the 3 diets had no difference in body weight over time, but female mice on KD and regular diet lost significant weight. When given oral sugar, blood sugar in males was similar for up to 90 minutes but female mice on the KD had higher blood sugar in response. Liver weight and markers of liver disease were reduced in both sexes, but KD-fed mice had more fats in their blood. When insulin secreting cells were removed and tested for response to sugar, insulin was not different; however, the opposing hormone, glucagon was lower in KD-fed mice. Together, while KD intervention was effective at improving body weight and liver health (females) or liver health alone (males), it was unable to enhance insulin secretion.