title: Improvement of impaired counterregulatory hormone response and symptom perception by short-term avoidance of hypoglycemia in IDDM.
abstract: OBJECTIVE
  To test the hypothesis that impaired counterregulatory hormone response and symptom perception, induced by recurrent hypoglycemic episodes over 2 days, may be improved by short-term (2-day) avoidance of hypoglycemia. RESEARCH AND DESIGN: We examined two groups of insulin-dependent diabetes mellitus (IDDM) patients (n = 16), none of whom exhibited signs of peripheral or autonomic neuropathy. Two sequential euglycemic-hypoglycemic clamp studies were performed applying 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 evaluated. 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 introduced to detect adaptation effects caused by the study procedure per se.
  
  
  RESULTS
  This short-term avoidance of hypoglycemia caused improvement of the impaired counterregulatory hormone response during insulin-induced hypoglycemia involving adrenaline (P < 0.05), adrenocorticotrophic hormone (P < 0.03), and cortisol (P < 0.05). Improvement of hypoglycemia symptom awareness encompassed overall symptom perception (multiple analysis of variance, P < 0.04) and the automatic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05).
  
  
  CONCLUSIONS
  The previously reported compromised neuroendocrine counterregulation and symptom awareness, occurring as a consequence of repetitive hypoglycemic episodes over 2 days, may be improved by a single 2-day interval of strict avoidance of hypoglycemia
authors.affiliation: Department of Endocrinology and Chemical Pathology, Eberhard-Karls University Tuebingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lingenfelser
authors.forename: U
authors.initials: U
authors.lastname: Buettner
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Tobis
authors.forename: W
authors.initials: W
authors.lastname: Renn
authors.forename: R
authors.initials: R
authors.lastname: Kaschel
authors.forename: B
authors.initials: B
authors.lastname: Jakober
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis / Q000517:prevention & control*; D007328:Insulin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D008297:Male; D010465:Perception; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D004837:Epinephrine