Ambulatory blood pressure, endothelial perturbation, and microvascular complications in type 2 diabetes.

Diabetic vascular complications constitute leading causes of blindness, renal failure, and cardiovascular morbidity and mortality world-wide. We studied haemodynamic and structural abnormalities associated with the development of microvascular complications and evaluated the effect of intervention with antihypertensive agents on these risk factors and complications in type 2 diabetic patients (T2DM). Retinal thickness, urinary albumin excretion rate, and transcapillary escape rate of albumin were strongly associated in T2DM patients with maculopathy, suggesting that macular oedema is a marker of generalised vascular hyperpermeability in T2DM. Plasma from T2DM patients with maculopathy stimulated the expression of E-selectin in cultured endothelial cells. Reduced nocturnal blood pressure decline ("non-dipping") and elevated pulse pressure (PP) were associated with micro- and macrovascular complications and predicted progression of nephropathy in T2DM subjects. Non-dipping and elevated PP were associated with increased plasma levels of markers of endothelial activation in T2DM patients, suggesting that endothelial perturbation could represent a pathophysiological link between these haemodynamic risk factors and the development of vascular complications in T2DM. 4 months treatment with losartan 50 mg o.d. did not ameliorate macular oedema in T2DM patients with maculopathy. 12 months dual blockade of the renin-angiotensin system with candesartan and lisinopril reduced ambulatory PP levels compared with high-dose lisinopril monotherapy in hypertensive T2DM subjects.