The effect of selective beta 1-blockade on glucose thresholds for release of counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus.
To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of diabetes 5-18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metoprolol and once with placebo, in random order. With the beta 1-selective blockade, epinephrine release was triggered at a significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p less than 0.01) with the beta 1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the beta 1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms.