title: Differential regulation of counterregulatory hormone secretion and symptoms during hypoglycemia in IDDM. Effect of glycemic control.
abstract: OBJECTIVE
  To determine 1) if there was a differential effect of glycemic control on individual counterregulatory hormone responses to hypoglycemia in patients with insulin-dependent diabetes mellitus (IDDM), 2) whether these modifications affect hypoglycemic symptom perception, and 3) if there was a level of glycemic control below which counterregulatory and symptomatic responses to hypoglycemia become consistently altered.
  
  
  METHODS
  We performed hypoglycemic clamp studies on 38 patients with IDDM and 38 healthy control subjects. Glucose was lowered from 5.0 to 2.2 mmol/l over 3 h in decrements of 0.6 mmol/l each 30 min. Epinephrine, cortisol, growth hormone (GH), glucagon, and symptom score were measured at each glucose plateau.
  
  
  RESULTS
  In IDDM patients, HbA1 levels were positively correlated with incremental epinephrine (r = 0.58, P < 0.001) and cortisol (r = 0.52, P < 0.01) responses, but inversely correlated with GH responses (r = -0.31, P < 0.05). The increase in symptom score correlated with the epinephrine response in the IDDM patients (r = 0.57, P < 0.001), but not in the healthy control subjects (r = -0.02, NS). In IDDM patients with HbA1 < or = 7.8% (n = 7), the epinephrine, cortisol, and symptomatic responses to hypoglycemia were blunted, but GH secretion was preserved.
  
  
  CONCLUSIONS
  These data suggest that 1) there is differential regulation of counterregulatory hormone secretion that is dependent on the level of glycemic control, 2) epinephrine is an important determinant of symptom perception in IDDM patients, but not in healthy control subjects, and 3) multiple defects in counterregulatory hormone secretion and symptom perception are consistently observed in patients with HbA1 levels < or = 7.8%.
authors.affiliation: Department of Medicine, Joslin Diabetes Center, Boston, MA 02215.
authors.forename: B T
authors.initials: BT
authors.lastname: Kinsley
authors.forename: B
authors.initials: B
authors.lastname: Widom
authors.forename: D C
authors.initials: DC
authors.lastname: Simonson
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay
chemical_list: D001786:Blood Glucose; D013006:Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine