METICULOUS PREVENTION OF HYPOGLYCEMIA NORMALIZES THE GLYCEMIC THRESHOLDS AND MAGNITUDE OF MOST OF NEUROENDOCRINE RESPONSES TO, SYMPTOMS OF,AND COGNITIVE FUNCTION DURING HYPOGLYCEMIA IN INTENSIVELY TREATED PATIENTS WITH SHORT-TERM IDDM

To test the hypothesis that hypoglycemia unawareness is largely second ary to recurrent therapeutic hypoglycemia in IDDM, we assessed neuroen docrine and symptom responses and cognitive function in 8 patients wit h short-term IDDM (7 yr) and hypoglycemia unawareness. Patients were a ssessed during a stepped hypoglycemic clamp, before and after 2 wk and 3 mo of meticulous prevention of hypoglycemia, which resulted in a de creased frequency of hypoglycemia (0.49 +/- 0.05 to 0.045 +/- 0.03 epi sodes/patient-day) and an increase in HbA1c (5.8 +/- 0.3 to 6.9 +/- 0. 2%) (P < 0.05). We also studied 12 nondiabetic volunteer subjects. At baseline, lower than normal symptom and neuroendocrine responses occur red at lower than normal plasma glucose, and cognitive function deteri orated only marginally during hypoglycemia. After 2 wk of hypoglycemia prevention, the magnitude of symptom and neuroendocrine responses (wi th the exception of glucagon and norepinephrine) nearly normalized, an d cognitive function deteriorated at the same glycemic threshold and t o the same extent as in nondiabetic volunteer subjects. At 3 mo, the g lycemic thresholds of symptom and neuroendocrine responses normalized, and surprisingly, some of the responses of glucagon recovered. We con cluded that hypoglycemia unawareness in IDDM is largely reversible and that intensive insulin therapy and a program of intensive education m ay substantially prevent hypoglycemia and at the same time maintain th e glycemic targets of intensive insulin therapy, at least in patients with IDDM of short duration.