Project summary
Type 1 diabetes accounts for 10–15% of Australian diabetic patients. People with type 1 diabetes have chronically elevated levels of blood sugar and are dependent on intensive insulin therapy to lower and maintain blood sugar levels within a healthy range. However, the use of insulin to lower blood sugar levels is imperfect and can lead to dangerously low blood sugar levels (hypoglycaemia). Type 1 diabetic patients are prone to repeatedly experiencing hypoglycaemia, which results in a condition called hypoglycaemia unawareness, and is characterised by the inability of a person to detect and respond to a hypoglycaemic event. They do not experience the physical hypoglycaemic symptoms, and the brain reflex is not activated to increase blood sugar levels. This condition, termed ‘hypoglycaemia-associated autonomic failure’ (HAAF), is life-threatening for type 1 diabetic patients.
Glucose is the major energy source for the brain under normal physiological conditions. However, during extended fasting, following exercise, or while on a high fat/low carbohydrate (ketogenic) diet, an alternative source of energy becomes available – ketone bodies. Ketone bodies are the product of fatty acid metabolism in the liver; they can cross the blood brain barrier and enter brain cells via specialised transporters. Ketones reduce the brain reflex response to a single episode of hypoglycaemia in healthy, non-diabetic, humans, but they also improve cognitive functions, suggesting a protective effect on the brain. The brain-protective effect of the ketogenic diet has proved beneficial for management of childhood drug-resistant epilepsy. Although ketones are effective in the preservation of brain cognitive functions under hypoglycaemic conditions in type 1 diabetic patients, the effects of ketones on brain reflex response to recurrent hypoglycaemia and the development of HAAF in this patient population are unknown. Enhanced availability of an alternative energy source (ketones) might be beneficial in the management of type 1 diabetes-associated hypoglycaemia and prevent the life-threatening consequences of severe hypoglycaemia and development of HAAF.
The aim of this project is to investigate the low carbohydrate ketogenic diet as a potential strategy in preventing the detrimental consequences of insulin-induced hypoglycaemia and the development of hypoglycaemia-associated autonomic failure (HAAF) in type 1 diabetes.