Impaired intrarenal dopamine production following intravenous sodium chloride infusion in Type 1 (insulin-dependent) diabetes mellitus

Summary Type 1 (insulin-dependent) diabetes mellitus is characterized by impaired sodium excretion following NaCl infusion. To investigate the possible role of dopamine in the impaired natriuresis in diabetes, intrarenal sodium handling, sodium excretion and urinary dopamine output, reflecting intrarenal dopamine formation, were studied following a 2 h 0.9% NaCl infusion (25 ml/kg) in eight diabetic patients and nine control subjects. The increase in sodium excretion in response to NaCl infusion was significantly (p<0.01) reduced in diabetic patients (19±7%) as compared with control subjects (46±8%). Fractional proximal tubular sodium reabsorption (determined by lithium clearance) decreased in the control group (p<0.001) following NaCl infusion but not in the diabetic group. Fractional distal tubular reabsorption decreased similarly in both groups. In response to NaCl urinary dopamine excretion increased by approximately 15% (p<0.01) in the control group but did not change in the diabetic group. The mean urinary dopamine excretion above basal was significantly greater in the control group (8.4±2.1 nmol/h) than in the diabetic group (–2.2±2.1 nmol/h; p<0.01). The urinary sodium/dopamine excretion ratio did not differ significantly between the two groups in the basal state or following NaCl. Baseline plasma levels of atrial natriuretic peptide did not differ between control and diabetic patients. In the control group atrial natriuretic peptide levels increased significantly (p<0.01) in response to NaCl whereas atrial natriuretic peptide levels did not change in the diabetic group. The results of this study show that patients with Type 1 diabetes have a blunted natriuresis in response to isotonic NaCl. This abnormality seems mainly to be due to impaired inhibition of proximal tubular sodium reabsorption, which may be the result of defective intrarenal dopamine mobilisation.