One out of three patients with type 1 diabetes has a reduced ability to perceive the onset of hypoglycemia. This condition is referred to as impaired awareness of hypoglycemia (IAH) and is usually the consequence of a process of habituation to recurrent hypoglycemia. IAH and the associated increased risk for severe hypoglycemia constitute a major burden for patients with type 1 diabetes and their relatives. Alterations in brain metabolism are most certainly involved in the pathogenesis of IAH, but the precise mechanisms underlyingIAH have remained unclear. As a consequence, targeted treatment options that do not deteriorate glycemic control are lacking, and more detailed knowledge regarding the pathophysiology of IAH is urgently needed. We hypothesized that the brain of patients with IAH has been conditioned to use an alternative fuel when plasma glucose levels are low. The overall aim of this thesis was to explore the role of lactate as a non-glucose alternative fuel in the development of IAH.