[The angiotensin II inhibition escape phenomenon in patients with type 2 diabetes and diabetic nephropathy]

Abstract

Aim: To study prevalence and clinical implications of paradoxical rise of angiotensin II (AII) level in blood plasma in long-term therapy with ACE inhibitors in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy (DN).

Material and methods: General clinical and hormonal (renin, AII, aldosteron, endothelin-1) examinations were conducted in 62 patients (37 males and 25 females) with DM-2 and DN on long-term ACE inhibitors. Escape of AII inhibition was defined as an increase in plasma AII more than 50 pg/ml corresponding to M+1SD in the control group (normotensive persons free of DM matched by age). Diet salt was controlled in all the patients.

Results: The patients received ACE inhibitors for 7.8 +/- 2.6 years. Plasma AII level in the control group was 34.5 +/- 16.1 pg/mL. The patients were divided into two groups according to their levels of AII: more than 50 pg/ml (group 1), less than 50 pg/ml (group 2). AII inhibition escape occurred in 24 patients (39%). No significant difference between the groups was registered by age, diabetes history, albuminuria, blood lipids, glycosylated hemoglobin, mean circadian blood pressure, duration of therapy with ACE inhibitors, intake of diuretics and beta-blockers. Patients of group 1 had a significantly higher cardiac interventricular septum thickness (p = 0.02), were more likely to have akinetic segments of the myocardium (p = 0.05), had lower 24-h urinary potassium (p = 0.03), insignificantly higher renal insufficiency. Plasma renin concentration was higher in group 1 (p = 0.004). AII did not correlate with aldosterone levels in both groups.

Conclusion: A relatively large percentage of type 2 diabetics with DN is due to AII inhibition escape. It may explain the lack of reno- and cardioprotective effect of rennin-angiotensin-aldosterone system blockade.