Decreased prorenin processing develops before autonomic dysfunction in type 1 diabetes

It is well documented that diabetic patients with chronic complications hav e decreased renin secretion and elevations in the renin precursor prorenin. It is uncertain, however, whether the abnormal processing of prorenin is r eflective of microvascular disease, hypertension, or autonomic neuropathy. Dechaux et al. (Transplant Proc. 18:1598-1599, 1986) observed abnormalities in prorenin processing in uncomplicated diabetes and suggested that it was the result of subclinical autonomic neuropathy. To test this hypothesis, w e measured renin, prorenin, and autonomic function in early type 1 diabetes at a time when there is little or no microvascular disease or hypervolemia . Thirty-seven patients (10 males, 27 females) enrolled 2-22 months after d iagnosis in a longitudinal study in which renin, prorenin, and autonomic fu nction were measured annually for 3 years. Forty-one age-matched control su bjects were also studied. PRA in the diabetic patients at the time of the second and third evaluation s was 1.71 +/- 0.24 ng angiotensin I/mL.h and 1.67 +/- 0.24 ng angiotensin I/mL.h, respectively, significantly lower (P < 0.05) than that of the contr ol subjects in whom PRA was 2.96 +/- 0.38 ng angiotensin I/mL.h. Prorenin w as not different in the diabetic patients in comparison with controls. The renin to prorenin ratio in the diabetic patients at the time of the first, second, and third evaluations was 0.260 +/- 0.03, 0.235 +/- 0.05, and 0.227 +/- 0.05, respectively, significantly lower (P < 0.01) than in control sub jects in whom the renin to prorenin ratio was 0.475 +/- 0.08. Despite this, at the time of the first and second evaluations, there was no evidence of autonomic dysfunction and no correlation between any test of autonomic func tion and the renin to prorenin ratio. At the time of the third evaluation, however, the intermediate frequency (0.04-0.15 Hz) power spectra while pati ents were supine (an index of sympathetic modulation of heart rate variabil ity) showed a highly significant (P < .001) correlation with the renin to p rorenin ratio. High frequency (0.15-0.40 Hz) spectra from supine patients a t the third evaluation also correlated with the renin to prorenin ratio (P < 0.01). We conclude abnormal processing of prorenin develops in diabetic patients p rior to microvascular disease, even before the first evidence of autonomic dysfunction. Although the latter may play a contributory role, additional a s yet unidentified mechanisms seem to interrupt the processing of prorenin in early diabetes.