Period: 2007 - 2011 
Funding: Dutch Diabetes Research Foundation
Research Institute: ICaR-VU
Contact: E. van Duinkerken , M.Sc

Is the presence or development of microvascular disease in type 1 diabetes related to changes in brain structure and cognitive function?

BACKGROUND: Recent literature showed that type 1 diabetes mellitus (T1DM) is related with mental slowing and loss of mental flexibility, as well as changes in the cerebral structure. Although changes seem mild to moderate and, therefore, are clinically less relevant they could hamper daily life of T1DM patients. There is less knowledge about the pathogenesis of these cerebral changes. For long, it was thought that hypoglycemic was one of the core mechanisms. Although the sort term effects of hypoglycaemia on the brain are beyond any doubt, large longitudinal follow-ups have failed to establish relations between hypoglycaemia and long term cerebral changes. The Diabetes Control and Complications Trial showed that chronic hyperglycemia has more long term impact on the brain than hypoglycaemia. This was supported by smaller cross-sectional studies. These studies compared two groups of T1DM patients, one with proliferative retinopathie as a marker of chronic hyperglycaemia and one group without apparent microvascular complications, to a group of healthy control subjects. It was found that T1DM patients with proliferative retinopathy performed worse on cognitive tests and had lower volumes of grey and white matter in the brain. Unfortunately, the sample size was too small to discriminate between both patient groups and T1DM patients without apparent microvascular complications and healthy controls.

AIM: The aim of this study is to determine in a large sample whether microvascular disease, as a marker of chronic hyperglycaemia, is related to cognitive deterioration, cerebral structural and functional changes.

METHODS: Fifty T1DM patients without apparent microvascular complications and 50 T1DM patients with proliferative retinopathy, as a marker of chronic hyperglycaemia, and possible other microvascular complications are compared to 50 healthy control subjects. To determine cerebral structure and MRI-scan is performed with a focus on grey and white matter structure. Magnetoencephalography is used to measure cerebral communication and neuropsychological assessment is performed to determine cognitive functioning. To improve the understanding of the underlying mechanisms, blood is drawn for APO E genotyping, urine samples are collected for measures of oxidative stress and cortisol, marco- and microvascular and ophthalmological measures are performed. To determine the effects of development of microvascular disease and periods of prolonged hyperglycaemia all measures will be repeated after a period of 6 years after baseline.