HYPOGLYCEMIA UNAWARENESS IN IDDM

OBJECTIVE - To assess the characteristics of patients with hypoglycemi a unawareness (development of neuroglycopenia without appropriate prio r autonomic warning symptoms) and its predisposing factors. RESEARCH D ESIGN AND METHODS - We studied 43 insulin-dependent diabetes mellitus patients who were objectively categorized as having or not having hypo glycemia using the stepped hypoglycemic clamp technique in which plasm a glucose was clamped at plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l and a statistical criterion (onset of autonomic warning symptoms at a pla sma glucose concentration 2 SD below normal) and examined their clinic al characteristics and hormonal, symptomatic, and cognitive responses. RESULTS - Eleven (26%) of the patients were classified as having hypo glycemia unawareness. Compared with the other patients, unaware patien ts had a lower HbA(1c) level (P < 0.01), a longer duration of diabetes (P < 0.01), and a history of more severe hypoglycemia (P < 0.003). Du ring experimental hypoglycemia, counterregulatory hormone responses, n euroglycopenic symptoms, and cognitive dysfunction all began at lower plasma glucose concentrations in unaware patients (P < 0.01, 0.03, and 0.01, respectively). Moreover, although the magnitudes of their plasm a catecholamine responses and autonomic symptoms were reduced (both, P < 0.01), the plasma catecholamine levels at which autonomic symptoms began was not altered. Finally, as seen from glucose infusion rates ne cessary to maintain identical plasma glucose levels, patients with hyp oglycemia unawareness had increased sensitivity to insulin (P < 0.001) . CONCLUSIONS - Our results confirm an association between hypoglycemi a unawareness and duration of diabetes, glycemic control, and occurren ce of severe hypoglycemia, and in addition provide evidence that both autonomic and neuroglycopenic symptoms are affected and that insulin s ensitivity is increased, but beta-adrenergic sensitivity is not dimini shed.