Oxidative stress and autonomic nerve function in early type 1 diabetes

Abstract

The biochemical mechanisms by which hyperglycemia causes microvascular disease and neuropathy are poorly understood. Experimental studies have established that oxidative stress is present in diabetic rodents with neuropathy, and that antioxidant therapy is protective. Oxidative stress is also present in human diabetes, but its clinical importance is uncertain. We examined several biochemical measures of oxidative stress in 37 patients with recent-onset (less than 2 years) type 1 diabetes annually in a 3-year longitudinal study. We also performed a comprehensive annual evaluation of somatosensory and autonomic nerve function. A total of 41 control subjects were studied. Malondialdehyde excretion, a measure of lipid peroxidation, was 1.5l ± .1 μmol/g creatinine in the control subjects, but 2.43 ± . 3 in the diabetic patients in year one, 2.39 ± .2 in year two and 1.92 ± .15 in year three, which was different from controls across all years; p < .005. Serum NOx (nitrate and nitric) was 34.0 ± 4.9 μmol/L in the controls, but 52.4 ± 5 in the diabetics in year one, 50.0 ± 5.1 in year two, and 49.0 ± 5.2 in year three, which was different from controls; p < .01. We measured sudomotor function and observed that the poorly controlled diabetic patients had relatively increased sweating above the waist and relatively decreased sweating below the waist, a typical pattern for sympathetic nerve injury. The ratio of sweating above to sweating below the waist was .385 ± .04 in controls, 0.70 ± .14 in diabetic patients in year one, .51 ± .14 in year two and .496 ± .12 in year three (different from controls; p < .01 across all years). Urinary MDA correlated negatively with total sweat (r = -39, p < .01); NOx also correlated negatively with total sweat (r = -.34, p < .025). Abnormalities in the processing of renin (the renin/prorenin ratio), a test of renal sympathetic neurons, was also documented in early type 1 diabetes. Oxidative stress and excessive serum NOx are associated with sympathetic dysfunction in early type 1 diabetes.