Effect of glycemic control on glucose counterregulation during hypoglycemia in NIDDM

OBJECTIVE - We examined the effect of glycemic control of NIDDM on counterregulatory hormone responses to hypoglycemia and compared the effect 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 control subjects were studied. All subjects underwent a stepped hypoglycemic-hyperinsulinemic clamp study during which plasma glucose levels were 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, norepinephrine, glucagon, ACTH, cortisol, and growth hormone [GH]) were measured, and a symptom survey was administered during the last 10 min of each 30-min interval. RESULTS - The threshold for release of epinephrine, norepinephrine, ACTH, and cortisol occurred at higher plasma glucose levels in NIDDM than in IDDM patients (P < 0.05-0.01). The glucose threshold for release of epinephrine and norepinephrine correlated with 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 glucose level in NIDDM versus IDDM patients (P < 0.05-0.01). At the nadir level of hypoglycemia, glucagon, ACTH, and cortisol levels were all higher 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 counterregulatory hormones at a higher plasma glucose level than patients with IDDM. In addition, subjects with NIDDM maintain their glucagon response to hypoglycemia. These data suggest that patients with NIDDM may be at reduced risk of severe hypoglycemia when compared with a group of IDDM patients in similar glycemic control, thus providing a more favorable risk-benefit ratio for intensive diabetes therapy in NIDDM.