The effects of hypoglycaemia on vascular disease and the brain

Abstract

Hypoglycaemia is the commonest and most feared side - effect of insulin therapy for diabetes, which is increased during strict glycaemic control. It can have detrimental effects on many aspects of cerebral function, but also provokes widespread changes in blood components and vascular flow such that theoretical concerns have been raised regarding its potential effects on the vasculature of people with diabetes. The aims of this thesis were: (a) to further examine the effects of hypoglycaemia on cognitive function, specifically to assess the effects on spatial abilities, and (b) to explore the potential effects of hypoglycaemia on several parameters that influence vascular function.

Spatial ability was assessed using the French and Ekstrom Kit of Factor Referenced (cognitive) Tests in 16 subjects with type 1 diabetes during euglycaemia and hypoglycaemia, which was induced using the hyperinsulinaemic glucose clamp technique. Vascular function was evaluated in a preliminary study by assessing the endothelin response to acute hypoglycaemia in 20 subjects with type 1 diabetes. Subsequently, 16 adult human subjects with type 1 diabetes and 16 subjects without diabetes were studied during hypoglycaemia and euglycaemia with measurement of an extensive battery of tests relevant to vascular function (soluble markers of platelet function, coagulation, and inflammation). Flow cytometry was used to assess the effects of hypoglycaemia and euglycaemia on platelet - monocyte aggregation, CD40 expression on monocytes and CD40 ligand expression on platelets, as these parameters are known to play a role in the initiation and progression of atherogenesis and vascular disease.

Results have indicated that spatial ability was significantly affected during hypoglycaemia, which is relevant to the everyday activities of people with diabetes. In response to hypoglycaemia, significant changes were observed in several intra- vascular indices that could compromise vascular function and exacerbate vascular disease. These findings are of concern given the fact that the main objective of optimal glycaemic control in diabetes is to prevent the development and progression of micro- and macrovascular disease. This research provides a basis for further studies to investigate this concept in greater detail, and adds to the body of evidence demonstrating the importance of avoiding hypoglycaemia while maintaining optimal glycaemic control.