ESPE Abstracts (2015) 84 S1.2

Diabetes Dysglycaemia, Cognition and the Developing Brain

Fergus Cameron

Royal Children’s Hospital, Melbourne, Victoria, Australia

Glucose is the preferred metabolite of the brain with 25% of circulating blood glucose in adults destined for cerebral metabolism. It is intuitive then that type 1 diabetes mellitus (T1DM), a disorder characterised by perturbations in blood glucose (‘dysglycaemia’), should cause acute and chronic brain dysfunction. These cognitive and affective impacts appear to be greatest in the developing brain of children and adolescents with T1DM. Aspects of diabetic dysglycaemia that appear to be most significant are hypoglycaemia, hyperglycaemia and diabetic ketoacidosis (DKA). Some early in vitro work suggest that glycaemic variability may also play a significant role in neural cell injury. Prospective observational data from the point of diagnosis to neuromaturation in the Royal Children’s Hospital Diabetes Cohort Study revealed a rather lamentable ‘rule of thirds’- one third of subjects developed a DSM IV threshold mental health disorder, one third did not complete secondary schooling and one third did not continue in adult care after transition. This was coincident with a 0.3 SD loss of full scale IQ and changes in regional brain volumes. More recent functional imaging studies have provided insight into some of the mechanistic aspects of dysglycaemia-induced brain injury. DKA at the point of diagnosis is associated with acute grey and white matter volume and spectroscopic changes that are associated with neurocognitive outcome in the medium term. Clamp studies combined with MRI have shown that hypo- and hyperglycaemia result in distinct regional changes in brain perfusion and metabolic activity. Potential synergies of chronic and additive dysglycaemic insults are difficult to quantitate largely due to an inability to fully record all aspects of glycaemic perturbation over a life course. In addition to this, pre-conditioning and programming may also play significant mediating roles. However, developmental age at the time of diabetes onset appears to have a critical influence upon outcome. A nascent understanding of mechanism of neural injury is providing some insights as to potential non-glycaemic interventions that might be used to protect the developing brain.

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