Norepinephrine secretion and production in diabetic autonomic neuropathy

Orthostatic hypotension (OH) in patients with diabetic autonomic neuropathy may result from sympathetic neuronal dysfunction and inadequate norepinephrine (NE) release as patients shift from the supine to an upright posture. The biochemical basis for this physiological abnormality is not understood. We measured basal supine NE secretion and production in 10 diabetic patients with OH, 9 diabetic patients without OH, and in 13 age-matched normal subjects. Apparent NE secretion, the rate at which NE enters the bloodstream, was 1.22 +/- 0.24 (SEM) nmol/m2 X min in the diabetic patients with OH, significantly lower than in the diabetic patients without OH and normal subjects in whom apparent NE secretion rates were 2.27 +/- 0.48 and 1.86 +/- 0.12 nmol/m2 X min, respectively. NE production, estimated from integrated NE metabolite excretion, was 10.2 +/- 0.85 nmol/mg creatinine in the diabetic patients with OH, which was significantly lower (P less than 0.01) than that in the diabetic patients without OH and normal subjects in whom NE production was 14.8 +/- 1.8 and 16.9 +/- 1.2 nmol/mg creatinine, respectively. These data demonstrate that supine basal apparent NE secretion and NE production are decreased in patients with OH secondary to diabetic autonomic neuropathy.