Glucoregulation during and after intense exercise: Effects of beta-adrenergic blockade in subjects with type 1 diabetes mellitus

In intense exercise (>80% maximum oxygen uptake) a huge, up to 8-fold incre ase in glucose production (Ra) is tightly correlated to marked increases in plasma norepinephrine (NE) and epinephrine. Both Ra and glucose uptake (Rd ) are enhanced, not reduced, during beta-adrenergic blockade in normal subj ects. beta-Blockade also caused a greater fall in immunoreactive insulin (I RI) during exercise, which could, in turn, have increased Pa directly or vi a an increased glucagon/insulin ratio. To control for adrenergic effects on endogenous insulin secretion, we tested type 1 diabetic subjects (DM) made euglycemic by overnight iv insulin that was kept constant in rate during a nd after exercise. Their responses to postabsorptive cycle ergometer exerci se at 85-87% maximum oxygen uptake for approximately 14 min were compared t o those of similar male control (CP) subjects. Six DM and seven CP subjects received iv 150 mu g/kg propranolol over 20 min, then 80 mu g/kg.min from -30 min, during exercise and far 60 min during recovery. Plasma glucose inc reased from similar resting values to peaks of 6.8 mmol/L in DM and 6.5 mmo l/L in CP, then returned to resting values in CP within 20 min, but in DIM, remained higher than in CP from 8-60 min (P = 0.049). Ra rose rapidly unti l exhaustion, to 13.3 mg/kg.min in CP and 11.6 in DM (P = NS). Pa declined rapidly in recovery, although somewhat more slowly in DM (P = 0.013 from 2- 15 min). The Rd increased to 10.6 in CP and 9.2 mg/kg min in DM (P = NS), t hen declined similarly in early recovery, but remained higher in CP from 50 -100 min (P = 0.05). The rises in plasma glucose during exercise in both gr oups were thus due to the increments in Rd less than those in Pa. The highe r recovery glucose in DM was due to the slower decline in Ra and the lower Rd in later recovery. IRI was higher in DM than in CP before exercise (P = 0.011), and whereas it decreased in CP (P < 0.05), it increased approximate ly 2-fold in DM, thus being higher throughout exercise (P = 0.003). The glu cagon/insulin ratio was unchanged in DM, but increased in CP during exercis e (P = 0.002). NE showed a rapid, marked increment during exercise to peak values of 23.7 nmol/L in CP and 25.7 nmol/L in DIM (P = NS), and epinephrin e showed parallel responses. Both correlated significantly with the Ra resp onses. In summary, the Ra responses of both DM and CP during exercise were greater than those of control unblocked subjects (previously reported) desp ite higher IRI (all exogenous) in DM. This suggests an important contributi on of direct a-adrenergic stimulation to this Pa effect.