Reduced Plasma Aldosterone Concentrations in Randomly Selected Patients with Insulin‐dependent Diabetes Mellitus

Abstract

Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +/- standard deviation: 4.10 +/- 0.36 vs 3.89 +/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +/- 4 vs 140 +/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

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

“…We found lower aldosterone levels despite similar PRA, resulting in an increased PRA/aldosterone ratio in type 1 DM, as reported earlier [3,4,6,11]. Notably, in a study in normoalbuminuric type 1 DM with glomerular hyperfiltration, others found an elevated PRA/aldosterone ratio to be the result of an increased PRA with normal aldosterone levels [2].…”

“…Nonetheless, plasma renin activity (PRA) has been reported to be increased [2,3], unaltered [4–6] or decreased [7,8], whereas plasma aldosterone levels have been reported to be normal [2,9,10], increased [4] or low [6,8,11] in DM. Furthermore, the PRA/aldosterone ratio, as an indicator of aldosterone responsiveness to endogenous renin‐angiotensin action, can be estimated to be increased [2–4,6,11], although a normal [5,8,9] ratio has also been observed. Several factors could be involved in the discrepancies between the above‐mentioned studies, as patients were heterogeneous with respect to the type of DM and the presence of diabetes‐associated complications.…”

“…There is evidence for an enhanced activity of local RAAS systems, possibly resulting in a reduction of systemic RAAS activity in DM [1]. Nonetheless, plasma renin activity (PRA) has been reported to be increased [2,3], unaltered [4 -6] or decreased [7,8], whereas plasma aldosterone levels have been reported to be normal [2,9,10], increased [4] or low [6,8,11] in DM. Furthermore, the PRA / aldosterone ratio, as an indicator of aldosterone responsiveness to endogenous renin-angiotensin action, can be estimated to be increased [2 -4,6,11], although a normal [5,8,9] ratio has also been observed.…”

Role of p90 Ribosomal S6 Kinase–Mediated Prorenin-Converting Enzyme in Ischemic and Diabetic Myocardium

“…Measurement of angiotensin (Ang) II and its upstream components of the RAS has been complicated by the rapid degradation of these peptides 4,5 and the local regulation of this production within specific vascular tissues and lesions. 6 Therefore, reports on the effects of diabetes on plasma and the tissue RAS, including Ang II levels, are controversial, [7][8][9] and interpretation of these changes is limited by the potential downstream modulation of renin and Ang II production and stability.…”

Angiotensin I-Converting Enzyme: A Pathogenetic Role in Diabetic Renal Damage?

“…PRA was reported to be increased [11,12], unaltered [13,[58][59][60][61] or decreased [20] in diabetes mellitus, whereas plasma aldosterone levels have been reported to be normal [11,13,14], increased [12,58] or low [59,62,63]. Furthermore, the PRA/aldosterone ratio, as an indicator of aldosterone responsiveness to endogenous renin-angiotensin action, has been reported to be increased in diabetes mellitus [10,11,58,59,63] although a normal [60,62] ratio has also been reported. In long standing, complicated diabetes mellitus hypo-aldosteronism appears to be linked to hypo-reninism.…”