Secretion of Atrial Natriuretic Peptide in Patients with Non-Insulin-Dependent Diabetes Mellitus and Effect of Autonomic Neuropathy on it

Abstract

In order to clarify the mode of atrial natriuretic peptide (ANP) release and the effect of autonomic nerve function on ANP release, we measured plasma ANP concentrations in response to hypertonic saline infusion in patients with non-insulin-dependent diabetes mellitus (NIDDM) having or not having autonomic neuropathy (AN). Studies were made on 72 normal subjects (male 44, female 28; 53.0 +/- 0.9 yr.), and 63 patients with NIDDM (male 36, female 27; 56.9 +/- 2.1 yr.). The patients with NIDDM were divided into two groups: Group A was 48 diabetics without AN, and Group B was 15 diabetics with AN. Six patients selected randomly from each group and 6 normal subjects were given an infusion of hypertonic saline (2.5% NaCl) at a rate of 0.25 ml/min/kg over 45 min. Autonomic nerve function was estimated by clinical symptoms, coefficient of variation of R-R intervals (CVR-R), Valsalva test and Schellong test. Plasma ANP concentration was measured by a sensitive and specific radioimmunoassay (RIA) after extraction using SEP-PAK C18 cartridge reported previously. The mean plasma concentration of ANP was 20.7 +/- 1.8 pg/ml (mean +/- SEM) in normal subjects, 24.3 +/- 2.4 pg/ml in NIDDM patients without AN, and 26.4 +/- 3.6 pg/ml in NIDDM patients with AN. There was no significant difference in these levels among the 3 groups. The fasting plasma concentration of ANP in diabetics as well as in normal subjects increased parallel with age. In 12 diabetics, plasma concentrations of ANP significantly elevated from 27.6 +/- 2.0 pg/ml to 149.4 +/- 29.8 pg/ml at 60 min after start of hypertonic saline infusion as compared with 6 normal subjects in whom the levels increased from 15.6 +/- 2.9 pg/ml to 34.1 +/- 5.7 pg/ml at 75 min. On the other hand, the plasma ANP concentration in response to hypertonic saline infusion in NIDDM patients with AN (71.8 +/- 14.4 pg/ml, at 60 min) was lower than that in NIDDM patients without AN (224.2 +/- 38.2 pg/ml, at 60 min). Area under the curve (AUC) of plasma ANP of NIDDM patients with AN after hypertonic saline infusion was 6560 +/- 879.6 pg.min/ml (normal subjects, 2575.6 +/- 444.6 pg.min/ml), which was significantly lower than that of NIDDM patients without AN (13757.8 +/- 1148.4 pg.min/ml). Moreover, there was a positive correlation between AUC and CVR-R in patients with NIDDM. These results indicate that the response of plasma ANP to hypertonic saline infusion in NIDDM patients is significantly higher than in normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)