EFFECT OF GLYCEMIC CONTROL ON GLUCOSE COUNTERREGULATION DURING HYPOGLYCEMIA IN NIDDM

OBJECTIVE - We examined the effect of glycemic control of NIDDM on cou nterregulatory hormone responses to hypoglycemia and compared the effe ct with that seen in patients with IDDM. RESEARCH DESIGN AND METHODS - Eleven subjects with NIDDM and eight age- and weight-matched control subjects and ten subjects with IDDM and ten age- and weight-matched co ntrol subjects were studied. All subjects underwent a stepped hypoglyc emic-hyperinsulinemic clamp study during which plasma glucose levels w ere lowered in a stepwise manner from 5.0 to 2.2 mmol/l in steps of 0. 6 mmol/l every 30 min. Counterregulatory hormones (epinephrine, norepi nephrine, glucagon, ACTH, cortisol, and growth hormone [GH]) were meas ured, and a symptom survey was administered during the last 10 min of each 30-min interval. RESULTS - The threshold for release of epinephri ne, norepinephrine, ACTH, and cortisol occurred at higher plasma gluco se levels in NIDDM than in IDDM patients (P < 0.05-0.01). The glucose threshold for release of epinephrine and norepinephrine correlated wit h glycemic control as measured by glycosylated hemoglobin (P < 0.05-0. 01). However, for a given level of glycemic control, the threshold for release of epinephrine and norepinephrine occurred at a higher glucos e level in NIDDM versus IDDM patients (P < 0.05-0.01). At the nadir le vel of hypoglycemia, glucagon, ACTH, and cortisol levels were all high er in NIDDM compared with IDDM subjects, whereas GH levels were lower. CONCLUSIONS - Glycemic control alters counterregulatory responses to hypoglycemia in NIDDM as has been previously reported in IDDM. However , at similar levels of glycemic control, NIDDM patients release counte rregulatory hormones at a higher plasma glucose level than patients wi th IDDM. In addition, subjects with NIDDM maintain their glucagon resp onse to hypoglycemia. These data suggest that patients with NIDDM may be at reduced risk of severe hypoglycemia when compared with a group o f IDDM patients in similar glycemic control, thus providing a more fav orable risk-benefit ratio for intensive diabetes therapy in NIDDM.