STIMULUS SPECIFICITY OF DEFECTS IN COUNTERREGULATORY HORMONE-SECRETION IN INSULIN-DEPENDENT DIABETES-MELLITUS - EFFECT OF GLYCEMIC CONTROL

Counterregulatory hormone responses to hypoglycemia are impaired in su bjects with insulin-dependent diabetes mellitus (IDDM) in strict glyce mic control. To determine whether these defects are specific for hypog lycemia, we examined counterregulatory hormone responses during a 3-h hypoglycemic hyperinsulinemic clamp (14.4 pmol/kg.min) that lowered pl asma glucose from 5.0 to 2.2 mmol/L in 9 well controlled IDDM patients (hemoglobin-Al, 7.5 +/- 0.8%), 9 poorly controlled patients (hemoglob in-Al, 12.5 +/- 1.5%), and 10 healthy volunteers. Counterregulatory ho rmone secretion was compared with responses to nonglucose secretagogue s for epinephrine and norepinephrine (cold presser test), ACTH (overni ght metyrapone test), and GH (L-arginine infusion). During hypoglycemi a, epinephrine and cortisol responses were lower in the IDDM group in strict glycemic control than those in the poorly controlled IDDM group or healthy volunteers (P < 0.05). In response to the cold presser tes t, the areas under the curve for epinephrine and norepinephrine were a lso reduced in the well controlled IDDM group (P < 0.05 vs. healthy vo lunteers). The ACTH response to hypoglycemia was not significantly red uced in the well controlled IDDM, whereas the response to metyrapone w as actually greater in this group (P < 0.05 us. poorly controlled IDDM ). GH responses to both hypoglycemia and arginine were highest in the well controlled diabetic patients. These data suggest that 1) the redu ced epinephrine responses in well controlled IDDM may not be specific for the hypoglycemic stimulus alone, but may also occur in response to other nonhypoglycemic stimuli; 2) cortisol responses to hypoglycemia are reduced in well controlled IDDM, whereas the ACTH response to a no n-hypoglycemic stimulus remains intact; and 3) GH responses to both hy poglycemic and nonhypoglycemic stimuli are preserved in well controlle d IDDM. The preservation of ACTH and GH responses to metyrapone and ar ginine, respectively, suggests adequate pituitary functional reserve i n IDDM patients in strict glycemic control in response to nonhypoglyce mic stimuli.