1. Diabetes mellitus is associated with high body sodium, but the pathogenetic mechanism is still unknown. The possibility that an abnormal renal handling of sodium, an abnormal responsiveness of sodium-modulating factors or a shift in the set point for sodium metabolism may contribute to or be associated with sodium retention was tested with an acute saline infusion.
2. A consecutive sample of 33 patients with stable non-azotaemic diabetes mellitus (24 insulin-dependent patients) and 30 normal control subjects was studied. Two litres of a 0.9% NaCl infusion were infused over 4 h. The urinary sodium excretion during the infusion and the next 18 h was analysed in relation to blood pressure, creatinine and lithium clearances, Na+−K+ co-transport, Na+−Li+ countertransport, plasma levels of renin, angiotension II, aldosterone, noradrenaline, adrenaline, atrial natriuretic factor and digoxin-like factor.
3. Diabetic patients and control subjects did not differ in blood pressure, body mass index, clearances of creatinine, sodium or lithium, intracellular sodium, Na+−K+ co-transport and Na+−Li+ countertransport, urinary and plasma levels of digoxin-like factor, plasma renin activity, angiotensin II, aldosterone, noradrenaline, adrenaline and atrial natriuretic factor. The intravenous saline infusion caused a similar natriuresis in diabetic patients and normal subjects; the renin—angiotension-aldosterone system was suppressed to a higher degree in diabetic patients than in normal subjects, whereas atrial natriuretic factor was stimulated to a similar extent; plasma digoxin-like activity was unchanged in both groups.
4. The natriuretic response to saline infusion was comparable between patients with insulin-dependent and non-insulin-dependent diabetes mellitus, those with lower or higher HbA1c levels and those with positive or negative family history of essential hypertension.
5. Using an acute saline infusion to study sodium-modulating factors, no abnormality can be detected which could represent a pathogenetic mechanism for sodium retention in diabetes mellitus. The normal natriuretic response to acute sodium loading in diabetic patients indicates that the set point for sodium homoeostasis may be normal despite the presence of high exchangeable sodium.