IMPROVEMENT OF IMPAIRED COUNTERREGULATORY HORMONE RESPONSE AND SYMPTOM PERCEPTION BY SHORT-TERM AVOIDANCE OF HYPOGLYCEMIA IN IDDM

OBJECTIVE - To test the hypothesis that impaired counterregulatory hor mone response and symptom perception, induced by recurrent hypoglycemi c episodes over 2 days, may be improved by short-term (2-day) avoidanc e of hypoglycemia. RESEARCH DESIGN AND METHODS - We examined two group s of insulin-dependent diabetes mellitus (IDDM) patients (n = 16), non e of whom exhibited signs of peripheral or autonomic neuropathy. Two s equential euglycemic-hypoglycemic clamp studies were performed applyin g stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l, at which the patients' awareness of and responses to hypoglycemia were evaluate d. In the intervention group (n = 11), three short-term hypoglycemic ( <2.2 mmol/l) episodes (days 1-3) preceded the first clamp study (day 4 ), whereas the second clamp study (day 6) followed a 2-day interval of strict avoidance of hypoglycemia. A control group (n = 5) was introdu ced to detect adaptation effects caused by the study procedure per se. RESULTS - This short-term avoidance of hypoglycemia caused improvemen t of the impaired counterregulatory hormone response during insulin-in duced hypoglycemia involving adrenaline (P < 0.05), adrenocorticotroph ic hormone (P < 0.03), and cortisol (P < 0.05). Improvement of hypogly cemia symptom awareness encompassed overall symptom perception (multip le analysis of variance, P < 0.04) and the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). CONCLUSIONS - The previo usly reported compromised neuroendocrine counterregulation and symptom awareness, occurring as a consequence of repetitive hypoglycemic epis odes over 2 days, may be improved by a single 2-day interval of strict avoidance of hypoglycemia.