Hormonal Counterregulation, Symptom Awareness, and Neurophysiological Function in Type 1 Diabetes During Insulin-induced Hypoglycaemia

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Abstract
To evaluate a putative differential impact of human (HI) and porcine (PI) insulin on human brain function we examined 10 Type 1 (insulin-dependent) diabetic patients without any signs of sensory or autonomic neuropathy. The glucose clamp technique was applied to achieve stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol l-1 on two occasions with randomized and blinded allocation of either HI or PI. At each of the plateaus, symptom awareness, hormonal counterregulation, and neurophysiological functions (primary sensory information processing of the auditory and somatosensory system) were recorded. The effect of both types of insulin on glucose metabolism and counterregulatory hormone response was almost identical. Catecholamines increased (adrenaline p less than 0.05; noradrenaline p less than 0.02) during hypoglycaemia, independent of the type of insulin being used. Symptom awareness increased significantly during the fall of blood glucose concentration. This effect was more pronounced (total symptom score 26 vs 2, p less than 0.05) with PI, but only during developing hypoglycaemia (3.3 mmol l-1-plateau). For brainstem auditory evoked potentials and somatosensory evoked potentials, all individual and averaged latencies and corresponding amplitudes were within the normal range. No effect of insulin type or blood glucose concentration on neurophysiological measures could be detected. Our results suggest a differential impact of HI and PI on human brain function with regard to symptom awareness, but not hormonal counterregulation. This direct effect of insulin on central nervous function does not involve the afferent transmission in the auditory and somatosensory system.