Hypoglycaemia: Studies on central and peripheral nerve function

Sammanfattning: Hypoglycaemia is an acute complication to insulin-treatment in type 1 diabetes mellitus, which affects many physiological parameters, deteriorates the cognitive function, and may lead to death. The aim of this thesis was to study nerve function, cognitive function and cerebral blood flow during and after hypoglycaemia in healthy subjects and to study certain aspects of a fall in blood glucose in patients with type 1 diabetes mellitus. In paper I, in patients with type 1 diabetes in a poor glycaemic control an insulin-induced rapid fall in blood glucose (18 to 9 mmol/L during 80 min) induced an increased cerebral blood flow by 17%. This is the same response as elicited in healthy subjects when blood glucose is lowered below 2.5 mmol/L, indicating that there was an adaptation to the high blood glucose level in our patients. In papers II and III, the recovery after hypoglycaemia (2.2-2.5 mmol/L) was studied in healthy subjects. The cognitive function was restored at the teast session starting 15 min after normalisation of blood glucose. The cerebral blood flow however remained elevated by 11% 1.5 hours after hypoglycaemia, indicating that cerebral blood flow is regulated by additional factors besides hypoglycaemia. In paper IV, the verve conduction velocity was decreased in the peroneal nerve after hypoglycaemia in healthy subjects, while it was unchanged in the median nerve and in the sural nerve. Hypoglycaemia may thus aggravate the nerve function in diabetes. In paper V, the QT interval in the electrocardiogram (ECG) was measured during and after hypoglycaemia in healthy subjects. The QT interval was prolonged to the upper normal range during hypoglycaemia, which is known to increase the risk for malignant ventricular arrhythmias. In paper VI, a group of cosecutive patients with type 1 diabetes and rapidly progressive severe retinopathy was compared retospectively with patients matched for age and diabetes duration. The patients with severe retinopathy had higher blood glucose level during the recorded 45 months before diagnosis, but the year before the diagnosis of severe retinopathy their blood glucose level decreased significantly to the same level as that of the control group during the observed time period. The year before the diagnosis they had minimal or no retinopathy. It seems plausible, that in these patients the longstanding high blood glucose level had induced retinal blood flow changes and unfavorable metabolic pathways, and that the decrease in blood glucose was detrimental yo yhe neural tissue, not being able to compensate for the relative hypoglycaemia.