ATRIAL-NATRIURETIC-PEPTIDE AND URINARY DOPAMINE OUTPUT IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24 h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion less-than-or-equal-to 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion greater-than-or-equal-to 300 mg/day). 2. The supine systolic blood pressure (mean+/-SD) was higher in patients with abnormal albuminuria (group 1: 140.9+/-27.4 mmHg; group 2: 158.1+/-26.4 mmHg; group 3: 166.7+/-23.9 mmHg; F=13.1, P<0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F=4.24, P<0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F=3.10, P<0.05, analysis of variance]. Using stepwise multiple regression analysis, plasma atrial natriuretic peptide concentration (r2=0.31, F=56.2, P<0.001) was associated with supine systolic blood pressure (beta=0.56, P<0.001), which was (r2=0.38, P<0.001) related to urinary albumin excretion (beta=0.23, P<0.001). In patients with urinary albumin excretion>30 mg/day, plasma atrial natriuretic peptide concentration was negatively correlated with urinary dopamine output (r=-0.25, P<0.02). 3. Based on these observations, we hypothesize that, in patients with non-insulin-dependent diabetes mellitus, defective dopamine mobilization in the renal tubules may cause impaired natriuresis with increased blood pressure. A compensatory rise in the plasma atrial natriuretic peptide concentration may then contribute to the development of abnormal albuminuria.