Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension

Ferdinando C. Sasso, MD, PHD, Ornella Carbonara, MD, Marcello Persico, MD, Dario Iafusco, MD, Teresa Salvatore, MD, Rosanna D'Ambrosio, MD, Roberto Torella, MD, Domenico Cozzolino, MD


Diabetes Care. 2002;25(11) 

In This Article

Abstract and Introduction

Objective: ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients.
Research Design and Methods: Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA1c, and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study.
Results: In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER.
Conclusions: These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects.

Diabetic nephropathy is the most common cause of renal failure in western society. Numerous factors predispose diabetic subjects to the development of renal disease. Hypertension is a major risk factor, and there is a direct correlation between glycemic control and the impairment of renal function.[1] Thus, strategies for preventing the progression of renal failure in diabetic patients, particularly in the early phase of nephropathy, include blood pressure (BP) as well as glycemic control.[2] Diabetic nephropathy develops gradually and slowly, finally leading to overt disease. The first indication of diabetic nephropathy is microalbuminuria, i.e., albumin excretion rate (AER) between 20 and 200 µg/min, in at least two of three consecutive measurements. This condition is referred to as "incipient nephropathy." In both type 1 and type 2 diabetes, microalbuminuria is a predictor of persistent proteinuria and early death from cardiovascular disease.[3]

The renin angiotensin system (RAS) is considered to be a paracrine regulator of renal function and blood flow, thus playing an important role in the progression of chronic renal disease, as seen in diabetic nephropathy. The effects of blocking the RAS with ACE inhibitors on delay or prevention of incipient to overt nephropathy and renal failure are widely recognized.[4]

Experimental studies and clinical trials have demonstrated that ACE inhibitors lower microalbuminuria independently of BP control;[5,6] thus, blocking RAS with ACE inhibitors is beneficial for hypertensive as well as normotensive microalbuminuric diabetic patients.

ACE inhibitors are more effective than conventional antihypertensive agents because they can modify both systemic and local pressure. However, ACE inhibitors also act on systems other than RAS, resulting in side effects, such as cough and angioneurotic edema, that reduce patient compliance.

Blocking angiotensin II receptors with the angiotensin type 1 receptor antagonist (AT1-RA) inhibits angiotensin more directly than ACE inhibitors.[7] By not interfering with any metabolic process in RAS, this different action mechanism may account for the excellent tolerability observed with the angiotensin II receptor antagonists.

Head-on comparison of equipotent doses of ACE inhibitors and angiotensin II receptor blockers in hypertensive nondiabetic patients produces equal reductions in mean arterial pressure and proteinuria.[8,9] Recently, some clinical trials demonstrated the effectiveness of AT1-RA in reducing AER in patients with hypertension, microalbuminuria, and type 2 diabetes.[10,11] Microalbuminuria can affect diabetic patients before the onset of hypertension. However, the possibility of slowing the progression of AER also in normotensive type 2 diabetic patients with microalbuminuria has not yet been tested. The aim of this study was to evaluate the effect of irbesartan, an angiotensin II receptor blocker, on microalbuminuria in normotensive and hypertensive type 2 diabetic patients.