Importance of Insulin in Subjective, Cognitive, and Hormonal Responses to Hypoglycemia in Patients With IDDM

Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU · m⁻² · m⁻¹, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU · m⁻² · min⁻¹. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P < 0.05 and P < 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P < 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P < 0.01). Levels of cortisol (P < 0.01) and growth hormone (P < 0.05) but not epinephrine were suppressed by the higher insulin infusion rate. We conclude that the prevailing insulin level does influence the perception of symptomatic and hormonal responses to low blood glucose levels. Cognitive impairment is dependent on level and duration of hypoglycemia.