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Introduction: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity., Methods: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test., Results: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During normoglycaemia, the frontal region was more activated in the low RAS group than in the high RAS group. During hypoglycaemia, the high RAS group was more activated in the pituitary gland than the low RAS group., Conclusion: Basal RAS activity influenced cerebral activity. Low RAS was associated with more pronounced cortical activation in all glycaemic conditions. High RAS was associated with pituitary activation during hypoglycaemia and post-hypoglycaemia, and this was associated with a greater growth hormone response.

The risk of severe hypoglycemia in patients with type I diabetes and high basal activity in the renin-angiotensin system (RAS) is significantly higher than in patients with low basal RAS activity. In healthy men, we tested the hypothesis that differences in spontaneous RAS activity are associated with differences in cerebral activity responses during mild hypoglycemia. A total of 10 healthy men with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O-PET (H(2)(15)O-positron emission tomography) study was conducted with a series of six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after hypoglycemia. The mean plasma glucose concentration was similar in both the groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.: 0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral activity in the frontal area and a higher cerebral activity in the entorhinal area that expanded to include the parahippocampal gyrus after hypoglycemia. Our findings suggest that the high RAS group to a lesser extent than the low RAS group activates areas involving executive function that may explain the correlation between high basal RAS activity and risk of severe hypoglycemia in type I diabetes.

Blurred vision and cognitive difficulties are prominent symptoms during acute insulin-induced hypoglycemia. Our hypothesis was that changes in cerebral activity reflect these symptoms. Positron emission tomography (PET) with oxygen-15-labelled water was used to measure relative changes in regional cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal counterregulatory response. During the low cognitive load, rCBF decreased in response to hypoglycemia in a large bilateral area in the posterior part of the temporal lobe, and rCBF increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus, the fusiform gyrus, thalamus, and the left inferior part of the frontal gyrus. During the high cognitive load, rCBF decreased bilaterally in a large region in the posterior part of the temporal gyrus and increased in the left and right anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and lingual gyrus, and left superior temporal gyrus. Visual impairment during hypoglycemia was associated with deactivation in the ventral visual stream. The anterior cingulate gyrus was activated during hypoglycemia in a load-dependent manner. Areas on the frontal convexity were differentially activated in response to the cognitive load during hypoglycemia. Our findings suggest that hypoglycemia induces changes in sensory processing in a cognition-independent manner, whereas activation of areas of higher order functions is influenced by cognitive load as well as hypoglycemia., ((c) 2009 Wiley-Liss, Inc.)