Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus:effects of RAAS stimulation

Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity and plasma aldosterone in uncomplicated type 1 diabetes mellitus by evaluating the effects of endogenous ( sodium restriction) and exogenous ( angiotensin I infusion) stimulation. Design Twenty-four type 1 diabetic patients and 24 matched healthy subjects were studied after 1 week of liberal sodium diet (200 mmol 24 h(-1)) and 1 week of low sodium diet (50 mmol 24 h(-1)). Angiotensin (Ang) I was infused at 4 and 8 ng kg(-1) min(-1) during both study days. Results During liberal and low sodium intake, plasma aldosterone was lower in type 1 diabetic patients compared with healthy subjects both at 08: 00 h (P <0.05) and after a 2-h euglycaemic clamp (P <0.05), despite similar PRA levels. The correlations between changes in PRA and changes in plasma aldosterone when shifting sodium intake were similar in both groups. During liberal sodium intake, the aldosterone levels after AngI infusion were lower in type 1 diabetic patients, whereas during low sodium they were not different. Conclusions Plasma aldosterone was deceased relative to PRA in uncomplicated type 1 diabetic patients, irrespective sodium intake. The responsiveness to sodium restriction was adequate and sodium restriction was able to overcome the decreased plasma aldosterone response to exogenous AngI, which was observed during liberal sodium in diabetic patients. The lower aldosterone is not secondary to diabetic complications and does not depend on the level of sodium intake

The influence of the ACE (I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus

Aim/hypothesis. The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To analyse these consequences, we assessed renal and systemic responsiveness to angiotensin I infusion, with the response to angiotensin II as reference. Methods. Uncomplicated Type 1 (insulin-dependent) diabetic patients with contrasting genotypes (11 II and 11 DD) were studied, during low (50 mmol/24 h) and liberal (200 mmol/24 h) sodium diet, during a euglycaemic clamp. Angiotensin I was infused at 4 and 8 ng.kg(-1).min(-1), 1 h each, followed by infusions of angiotensin II after a 2-h wash-out period. Results. During low sodium, DD-homozygotes showed higher blood pressure sensitivity to angiotensin I (DD 21+/-5% vs II 15+/-5%, p Conclusion/interpretation. This study showed that responses of blood pressure and renal haemodynamics to angiotensin I are increased in diabetic subjects carrying the DD-genotype. Genotype-associated differences in ACE concentrations could, under certain circumstances, have functional consequenses in uncomplicated Type 1 diabetes mellitus

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 (HbA(1c) <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 11βHSD 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 5α reductase activity, resulting in a decreased cortisol metabolic clearance. In type 1 diabetic and in healthy males, the 11βHSD setpoint is not affected by physiological variations in sodium intake

Short-term moderate sodium restriction induces relative hyperfiltration in normotensive normoalbuminuric Type I diabetes mellitus

Aims/hypothesis. Type I (insulin-dependent) diabetes mellitus is associated with an increased extracellular volume. Sodium restriction might seem a logical form of treatment but data on its renal effects is conflicting. We therefore studied the effects of sodium restriction on renal haemodynamics in uncomplicated Type I diabetes mellitus.Methods. Uncomplicated Type I diabetic patients (n = 24) and matched control subjects (n = 24) were studied twice in random order: after a week of 50 mmol or after 200 mmol sodium intake, respectively. The diabetic patients were studied under normoglycaemic clamp conditions. Glomerular filtration rate and effective renal plasma flow were measured as the clearances of iothalamate and hippuran, respectively.Results. During liberal sodium intake, glomerular filtration, effective renal plasma flow and filtration fraction were similar between the diabetic patients and the control subjects. Sodium restriction decreased the effective renal plasma flow in both groups, whereas glomerular filtration rate only decreased in the control subjects. Consequently, in the diabetic patients, the filtration fraction was increased on low sodium (4.1 +/- 8.4 %, p &lt;0.05 vs liberal sodium). As a consequence, filtration fraction (24.0 +/- 2.6 vs 22.1 +/- 2.0 %, p &lt;0.05) and glomerular filtration (119 +/- 14 vs 110 +/- 13 ml/min, p &lt;0.05) were higher in the diabetic patients than in the control subjects during sodium restriction.Conclusion/interpretation. Short-term moderate sodium restriction induces relative hyperfiltration in uncomplicated Type I diabetes. This could indicate an increased intraglomerular pressure. Sodium restriction could be an unfavourable preventive approach in diabetes mellitus but its long-term effects are not known.</p