Impact of Blood Pressure and Antihypertensive Treatment on Incipient and Overt Nephropathy, Retinopathy, and Endothelial Permeability in Diabetes Mellitus

Abstract

Diabetic nephropathy is the main cause of the increased morbidity and mortality in insulin-dependent diabetes mellitus (IDDM) patients. Elevated blood pressure accelerates and effective blood pressure reduction with beta-blockers and/or angiotensin-converting enzyme (ACE) inhibitors delays the progression of nephropathy and reduces albuminuria. All previous reports dealing with the natural history of diabetic nephropathy demonstrated a cumulative death rate between 50 and 77% 10 yr after onset of nephropathy. Effective antihypertensive treatment reduced the cumulative death rate to 15-20% 10 yr after onset of nephropathy. Recent randomized control studies indicate that ACE inhibition may delay and even prevent the development of diabetic nephropathy in normotensive IDDM patients with persistent microalbuminuria. Several cross-sectional and prospective studies suggest an association between elevated blood pressure and the development and progression of diabetic retinopathy. Furthermore, carotid insufficiency or other causes of unilaterally or bilaterally reduced retinal blood flow (pressure) diminish the development of diabetic retinopathy. Diabetic retinopathy is characterized by abnormal leakage of fluorescein through the blood-retinal barrier, an abnormality that can be reversed during antihypertensive treatment. It is well documented that elevated blood pressure, poor metabolic control, and diabetic microangiopathy independently enhance the endothelial leakage of plasma proteins in diabetes mellitus. A link between capillary hypertension, increased extravasation of plasma proteins, and the development and progression of diabetic microangiopathy has been suggested. Blood pressure reduction diminishes the extravasation of plasma proteins. The above results strongly support the case for early and effective treatment of arterial blood pressure elevation in diabetes.