Increased cerebral FDG‐PET uptake in type 1 diabetes patients with impaired awareness of hypoglycaemia

Abstract

Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state‐of‐the art neuroimaging techniques, we compared 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D‐IAH patients showed a pattern of increased FDG‐PET uptake with respect to NAH patients (P < .05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appeared to be unrelated to compensatory mechanisms as a result of reduced grey matter density or a neuroinflammatory state. We observed an abnormal increase in FDG‐uptake in T1D patients with IAH in brain regions strongly related to cognition. Because this hypermetabolic state correlated with IAH severity, its biological characterisation could reveal new preventive or therapeutic strategies. A possible mechanism could be that glucose transport is increased in hypoglycaemia unawareness to compensate for recurrent hypoglycaemia, although this need to be confirmed in further research.

Case report of 18F-FDG PET/CT features of hypoglycemic encephalopathy

“…Moreover, patients with IAH and T1D have abnormal hypermetabolism in brain regions strongly related to cognition. [6] In the present case of HE, 18 F-FDG PET/CT images on day 5 after admission showed significant hypermetabolism in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus, suggesting nerve cell damage in these areas. However, the follow-up PET/CT images 6 months later showed a significant decrease in FDG uptake in the lesions of the bilateral medial frontal gyrus, whereas no abnormality was observed in the lesions of the bilateral cerebellar cortex and dentate nucleus.…”

“…The lesions of patients with HE were not always deficient in FDG uptake after onset but had significantly increased glucose metabolism in the initial stage, which was also consistent with some literature reports. [6,7] 2. In the lesions, not all neurons damage is irreversible.…”

“…Moreover, patients with IAH and T1D have abnormal hypermetabolism in brain regions strongly related to cognition. [ 6 ]…”

“…HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. [ 6 ] We believe that such compensation occurs not only in normal cells around damaged cells but also in damaged cells. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal.…”