Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia

Abstract

Objective The incidence of both severe and asymptomatic hypoglycemia is increased threefold in intensively treated diabetic patients. To examine whether this reflects cerebral adaptation to low blood glucose levels, we investigated the effect of preceding glycemic experience on hormonal, EEG, and evoked potential responses to experimentally induced hypoglycemia with the slow-fall clamp. Research Design and Methods Three groups were examined: well-controlled diabetic patients and patients with insulinoma (group 1), poorly controlled diabetic patients (group 2), and nondiabetic subjects (group 3). Results The glucose threshold for epinephrine release was lower in group 1 (2.3 ± 0.1 vs. 3.0 ± 0.3 and 3.1 ± 0.1 mM, P < 0.02), and the peak epinephrine response was reduced (1.29 ± 0.36 vs. 5.48 ± 1 and 5.62 ± 1.2 nM, P < 0.01) compared with groups 2 and 3, whereas symptoms were not perceived until a lower blood glucose level had been reached (2.0 ± 0.2 vs. 3.3 ± 0.4 and 2.6 ± 0.2 mM, P < 0.01). Other counterregulatory responses were similarly delayed and diminished. In contrast, EEG changes that were compatible with hypoglycemia were detected in all subjects in group 1 (blood glucose 1.9 ± 0.1 mM) but in only two in group 2 and none in group 3, despite similar blood glucose nadirs. Conclusions The glycemic threshold for hormonal responses to hypoglycemia falls in individuals with intensively treated diabetes or insulinomas, but these patients are more likely to develop EEG abnormalities during hypoglycemia. This disparity helps explain the increased vulnerability of intensively treated patients to severe hypoglycemia.