Relationships Among Natriuresis, Atrial-natriuretic-peptide and Insulin In Insulin-dependent Diabetes

Insulin-dependent diabetic patients have a large exchangeable body sodium pool, secondary to sodium retention. The pathogenesis of impaired natriuresis in insulin dependent diabetes remains to be elucidated. The present study examines the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance to atrial natriuretic peptide action in determining sodium retention in normotensive and hypertensive insulin-dependent diabetic patients. Eight insulin-dependent diabetic patients had significantly higher daily sodium excretion rate (147 +/- 16 mmol/day; mean +/- SE) during conventional insulin treatment (daily plasma glucose: 11.6 +/- 1.2 mmol/liter; daily plasma insulin: 27 +/- 3-mu-U/ml) than during intensified insulin treatment (daily sodium excretion rate: 91 +/- 12, P < 0.01; daily plasma glucose: 6.8 +/- 0.7, P < 0.01; daily plasma insulin: 44 +/- 4, P < 0.01). Daily sodium excretion rate was also significantly lower (107 +/- 13, P < 0.01) in the same diabetic patients during intensified insulin treatment along with hyperglycemic clamp (daily plasma glucose: 12.8 +/- 0.3, NS; plasma insulin 48 +/- 4, P < 0.01). Seven control subjects had lower extracellular liquid volume than eight insulin-dependent diabetic patients (11.0 +/- 0.8 1/1.73 m2 vs. 14.8 +/- 0.9, P < 0.05) and also had baseline plasma atrial natriuretic peptide concentrations (18 +/- 5 pg/ml vs. 37 +/- 4, P < 0.05). Atrial natriuretic peptide response to saline challenge was blunted in insulin-dependent diabetic patients when saline was administered on the basis of body surface area (90 mmol/1.73 m2.90 min) but not when administered on the basis of extracellular liquid volume (ECV) (8.2 mmol/liter ECV.90 min). Continuous infusion of atrial natriuretic peptide in the same control and diabetic subjects (0.06-mu-g/kg.min.120 min) resulted in similar circulating concentrations of the hormone but in significantly lower sodium excretion rate in diabetic (from 185 +/- 19 to 193 +/- 21-mu-mol/1.73 m2 . min) than in control subjects (199 +/- 14 to 341 +/- 22, P < 0.01). Natriuretic action of atrial natriuretic peptide was similarly impaired in a group of eighteen hypertensive insulin-dependent diabetic patients in comparison with a matched group of seven hypertensive control patients. Angiotensin converting enzyme inhibitor treatment in these hypertensive diabetic patients decreased extracellular liquid volume and improved natriuretic response to atrial natriuretic peptide. We conclude that refractoriness to natriuretic action rather than impaired release of atrial natriuretic peptide can further deteriorate sodium retention in insulin dependent diabetes. This altered hormonal behavior could be primarily due to insulin-induced sodium retention and extracellular liquid volume expansion.