Endocrine Abstracts

The brain is dependent on a continuous supply of glucose as its source of energy, the rate-limiting step being the rate of transport across the blood-brain barrier. Glucose deprivation of the brain causes neuroglycopenia and rapid malfunction. This is demonstrated by the development of abnormal neurophysiological function with slowing of neural transmission and electroencephalographic changes, and by the progressive impairment of cognitive function, affecting several domains. The cognitive dysfunction is manifested as neuroglycopenic symptoms of hypoglycaemia, while autonomic (principally sympatho-adrenal) activation generates classical autonomic symptoms. The glycaemic threshold for onset of these symptoms can be modified in people with insulin-treated diabetes, with cerebral adaptation underlying the syndrome of impaired awareness of hypoglycaemia. Regional cerebral blood flow is also altered acutely during acute hypoglycaemia, with blood flow increased in the frontal cortex, so protecting the most vulnerable part of the brain. These regional vascular changes become permanent in people exposed to recurrent severe hypoglycaemia and in those with impaired awareness of hypoglycaemia. Severe brain damage during hypoglycaemia is rare.

Very young children are most susceptible to cognitive impairment resulting from severe episodic hypoglycaemia. Recurrent exposure to severe hypoglycaemia in middle-aged adults with type 1 diabetes appears to have a modest adverse effect on intellectual function, and neuroimaging with MRI has suggested an association with cortical atrophy. Further studies that examined cognitive function and neuroimaging in people who had developed type 1 diabetes in childhood or adolescence, found no correlation between hypoglycaemia exposure and cognitive performance, but revealed a relationship between poorer cognitive ability and the presence of microvascular disease (as retinopathy), implying that chronic hyperglycaemia may affect the brain. These diabetic subjects had a higher incidence of small punctate white matter lesions demonstrable on neuroimaging, which may represent premature ageing of the brain.