Decreased Prorenin Processing Develops before Autonomic Dysfunction in Type 1 Diabetes1

Author:

Hoeldtke Robert D.1,Bryner Kimberly D.1,Komanduri Padma1,Christie Ian2,Ganser Gary2,Hobbs Gerald R.3

Affiliation:

1. Departments of Medicine (R.D.H., K.D.B., P.K.), Morgantown, West Virginia 26506-9159

2. Mathematics (I.C., G.G.), Morgantown, West Virginia 26506-9159

3. Community Medicine and Statistics (G.R.H.), West Virginia University, Morgantown, West Virginia 26506-9159

Abstract

It is well documented that diabetic patients with chronic complications have decreased renin secretion and elevations in the renin precursor prorenin. It is uncertain, however, whether the abnormal processing of prorenin is reflective 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, we 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 diagnosis in a longitudinal study in which renin, prorenin, and autonomic function were measured annually for 3 years. Forty-one age-matched control subjects were also studied. PRA in the diabetic patients at the time of the second and third evaluations 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 control subjects in whom PRA was 2.96 ± 0.38 ng angiotensin I/mL·h. Prorenin was 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 subjects 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 function 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 patients were supine (an index of sympathetic modulation of heart rate variability) showed a highly significant (P < .001) correlation with the renin to prorenin ratio. High frequency (0.15–0.40 Hz) spectra from supine patients at the third evaluation also correlated with the renin to prorenin ratio (P < 0.01). We conclude abnormal processing of prorenin develops in diabetic patients prior to microvascular disease, even before the first evidence of autonomic dysfunction. Although the latter may play a contributory role, additional as yet unidentified mechanisms seem to interrupt the processing of prorenin in early diabetes.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference30 articles.

1. Low plasma renin activity in normotensive patients with diabetes mellitus: relationship to neuropathy.;Fernandez-Cruz Jr;Hypertension,1981

2. Altered synthesis of renin in patients with insulin-dependent diabetes: plasma prorenin as a marker predicting the evolution of nephropathy.;Amemiya;Diabetes Res Clin Prac,1990

3. Elevated levels of plasma prorenin (inactive renin) in diabetic and nondiabetic patients with autonomic dysfunction.;Misbin;J Clin Endocrinol Metab,1987

4. The significance of autonomic neuropathy in the elevation of inactive renin in diabetes mellitus.;Chimore;Clin Exp Hypertens,1987

5. Is impaired renin reactivity in diabetic children a first step in the development of autonomic neuropathy?;Dechaux;Transplant Proc,1986

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