Type 1 diabetes mellitus and the brain: influence of clinical complications and genetic factors on brain structure and cognitive function

Abstract

Type 1 diabetes mellitus is characterised by absolute insulin deficiency, chronic hyperglycaemia and intermittent hypoglycaemia consequent upon treatment with insulin. Severe hypoglycaemia, defined as hypoglycaemia sufficient to necessitate third party intervention for recovery, commonly complicates insulin therapy and repeated exposure may be detrimental to the brain. Microvascular disease, manifest as retinopathy, neuropathy or nephropathy, frequently complicates diabetes, the risk being related to long-term glucose control and increasing disease duration. Microvascular disease may also affect the cerebral circulation and could potentially compromise brain structure and intellectual performance. Type 1 diabetes commonly develops in childhood before full maturation of the central nervous system and the developing brain may exhibit relative vulnerability to damage as a consequence of exposure to severe hypoglycaemia, or the development of Diabetic Keto-Acidosis, in early childhood. Genetic factors influence the vulnerability of an individual to develop cognitive impairment following pathological processes known to disadvantage the central nervous system. Polymorphism of the Apolipoprotein-E gene has been identified as one such factor and is known to influence the prognosis and cognitive outcomes following a wide variety of cerebral insultsThe studies contained within this Thesis explore the long-term consequences the clinical factors described above on brain structure and the cognitive performance of young adults with Type 1 diabetes mellitus of long duration. The effects of polymorphism of the Apolipoprotein-E gene on the cognitive performance of young adults who have Type 1 diabetes mellitus are also evaluated.