Six juvenile diabetics [age, 31 ± 2 yr ( and SEM); duration of diabetes, 15 ± 4 yr], who showed signs of autonomic neuropathy (decreased beat-to-beat variation in heart rate during deep breathing), and seven control patients of similar age (27 ± 1 yr) and duration of diabetes (14 ± 2 yr) performed graded exercise on an ergometer cycle 3 h after breakfast and subcutaneous administration of insulin.

Plasma epinephrine increased significantly in both patient groups and was not significantly different at exhaustion [0.43 ± 0.17 ng/ml (neuropathy) vs. 1.07 ± 0.28 ng/ml (controls), P < 0.1]. Plasma norepinephrine levels increased significantly in control patients but not in autonomic neuropathy, and they were significantly different at exhaustion [1.43 ± 0.34 ng/ml (neuropathy) vs. 2.51 ± 0.26 ng/ml (controls), P < 0.05]. The relationships between plasma norepinephrine and epinephrine levels, respectively, and relative work load (expressed as oxygen uptake—in per cent—of individual maximal oxygen uptake) were shifted to the right in patients with autonomic neuropathy, indicating impaired sympathetic activity.

A significant decrease in plasma glucagon levels was found at low work loads (50 W and 75 W) in control patients but not in patients with autonomic neuropathy. At exhaustion, plasma glucagon levels were similar to resting levels in both patient groups. At exhaustion, plasma growth hormone and cortisol levels were significantly above preexercise levels only in control patients (50.5 ± 7.9 mU/L and 23.5 ± 2.9 ug/100 ml, respectively), and they were higher in these patients, P < 0.025 and P < 0.005, respectively, than in patients with autonomic neuropathy (24.4 ± 8.4 and 12.8 ± 1.6, respectively). Metabolic responses were similar in the two patient groups, as judged from plasma concentrations of glucose, lactate, free fatty acids, glycerol, and beta-hydroxybutyric acid.

In conclusion, diabetics with decreased beat-to-beat variation in heart rate displayed impaired responses of catecholamines, indicating a defective sympathoadrenal outflow, and of other glucoregulatory hormones during graded exercise.

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