Decreased cortisol production in male type 1 diabetic patients.

BACKGROUND: It is unclear whether cortisol production and the 11betaHSD-mediated cortisol to cortisone interconversion are different between type 1 diabetic patients and healthy subjects. MATERIALS AND METHODS: Fourteen male, nonobese, normotensive type 1 diabetic patients without severe complications (HbA1c < 8.5%) were studied twice during a daily sodium intake of 50 and 200 mmol, and were then compared with 14 individually matched healthy subjects. Cortisol production was assessed by the sum of urinary cortisol metabolite excretion. Urinary ratios of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydro-cortisone [(THF + allo-THF)/THE] and of free cortisol/free cortisone [UFF/UFE] were determined as parameters of 11betaHSD activity. RESULTS: Sum of urinary cortisol metabolite excretion during low- and high-salt diet was 7.4 +/- 2.5 vs. 7.7 +/- 2.3 nmol min-1 m-2 (NS) in diabetic patients and 9.7 +/- 2.1 vs. 11.2 +/- 4.1 nmol min-1 m-2 (NS) in healthy subjects, respectively (P < 0.05 vs. healthy subjects at both diets). The allo-THF excretion and allo-THF/THF ratios were lower in the diabetic than in the healthy males during both diets (P < 0.05). Urinary (THF + alloTHF)/THE and UFF/UFE were similar in both groups and remained unchanged after salt loading. CONCLUSIONS: The sum of urinary cortisol metabolite excretion as a measure of cortisol production is lower in nonobese, normotensive type 1 diabetic males with adequate glycaemic control and without severe complications, irrespective of sodium intake. We suggest that this is at least in part as result of diminished 5alpha reductase activity, resulting in a decreased cortisol metabolic clearance. In type 1 diabetic and in healthy males, the 11betaHSD setpoint is not affected by physiological variations in sodium intake.

Does a low-salt diet exert a protective effect on endothelial function in normal rats?

Sodium restriction is often used as an adjunct in the treatment of conditions characterized by endothelial dysfunction, such as hypertension and heart or kidney disease. However, the effect of sodium restriction on endothelial function is not known. Therefore, male Wistar rats were studied after a fixed salt diet had been maintained (low-salt group: 0.05% NaCl, n = 10; normal-salt group: 0.3% NaCl, n = 10) for 6 weeks. Blood pressure and sodium excretion values were measured once a week. Subsequently the rats were killed, the aorta was removed, and rings were cut. Endothelium-independent (sodium nitrite [SN]) and endothelium-dependent (acetylcholine [ACh]) vasodilator responses were assessed in the presence of indomethacin (a cyclo-oxygenase inhibitor) and in the presence or absence of NG-monomethyl-L-arginine (L-NMMA; a competitive inhibitor of nitric oxide [NO] synthase). Endothelium-independent vasodilatation was not different for the two salt groups. Endothelium-dependent vasodilatation, on the other hand, was different. The response to ACh was almost completely abolished by L-NMMA in the normal-salt group, whereas vasodilatation was partially preserved during L-NMMA in the low-salt group. Accordingly, the L-NMMA-sensitive contribution to ACh-dependent vasodilatation was smaller in the low-salt group. Thus, salt restriction induced a non-NO and non-prostaglandin-dependent vasodilating pathway. By exclusion this could be endothelium-derived hyperpolarizing factor, a pathway of vasculoprotective potential. Accordingly, the relative contributions of the different vasoactive endothelial pathways were affected by salt intake. Further research will be needed to clarify the nature and importance of this non-NO, non-prostaglandin-dependent pathway in the clinical setting as well.