Metabolic neuroimaging of the brain in diabetes mellitus and hypoglycaemia

Functional neuroimaging techniques can be used to study changes in regional brain activation, using changes in surrogate markers such as regional cerebral perfusion and rates of glucose uptake or metabolism. These approaches are shedding new light on two major health problems: the increasing burden of type 2 diabetes mellitus (T2DM), which is driven by the rising prevalence of insulin resistance and obesity; and recurrent intractable problematic hypoglycaemia, which is driven by the cognitive impairment that can occur in association with iatrogenic hypoglycaemic episodes. Some patients with diabetes mellitus lose awareness of being hypoglycaemic, which puts them at risk of severe hypoglycaemia as they are unlikely to take action to prevent the condition worsening. Involvement of corticolimbic brain and centres serving higher executive functions as well as the hypothalamus has been demonstrated in both situations and has implications for therapy. This Review describes the relevant principles of functional neuroimaging techniques and presents data supporting the notion that the dysregulation of central pathways involved in metabolic regulation, reward and appetite could contribute to problematic hypoglycaemia during therapy for diabetes mellitus and to insulin-resistant obesity and T2DM. Understanding these dysregulations could enable the development of novel clinical interventions.