MACRO-MICROANGIOPATHY AND ENDOTHELIAL DYSFUNCTION IN NIDDM PATIENTS WITH AND WITHOUT DIABETIC NEPHROPATHY

The Steno hypothesis suggests that albuminuria reflects widespread vas cular damage (proliferative retinopathy and severe macroangiopathy) du e to a generalized vascular (endothelial) dysfunction. We assessed thi s concept in NIDDM (non-insulin-dependent diabetic) patients with (13 female/ 39 male, age 60 +/- 7 years, group 1) and without (12 female/4 1 male, age 61 +/- 7 years, group 2) diabetic nephropathy compared to matched non-diabetic subjects (7 female/15 male, age 58 +/- 8 years, g roup 3). A 12-lead ECG was recorded and coded blindly using the Minnes ota Rating Scale; the World Health Organization cardiovascular questio nnaire was used to assess past and present evidence of myocardial infa rction, angina pectoris, stroke, and peripheral vascular disease (digi tal systolic blood pressure determination). The degree of diabetic ret inopathy was scored from fundus photography. The following variables w ere measured: transcapillary escape rate of albumin (initial disappear ance of intravenously injected I-125-labelled human serum albumin), pl asma concentrations of prorenin (radioimmunoassay) and serum concentra tions of von Willebrand factor (enzyme-linked immunoadsorbent assay). Prevalence of ischaemic heart disease (EGG reading) (49/20/5)% and per ipheral vascular disease as indicated by reduced systolic blood pressu re on big toe (69/30/14)% was significantly higher in group 1 vs group 2 (p < 0.01) and in group 2 vs group 3 (p < 0.01), respectively. The prevalence and severity of retinopathy was higher in group 1 vs 2 (p < 0.01). Transcapillary escape rate of albumin (%/h) was elevated in gr oup 1 and 2 as compared to control subjects: 7.9 (4.3-13.7); 7.4 (3.7- 16.4) vs 6.0 (3.4-8.7), (p < 0.005), respectively. Plasma prorenin act ivity (IU/ml) was raised in group 1 and group 2 as compared to group 3 : 272 (59-2405); 192 (18-813), and 85 (28-246), p < 0.001, respectivel y. Serum von Willebrand factor (IU/ml) was elevated in group 1 as comp ared to group 2 and 3: 2.07 (0.83-4.34); 1.60 (0.30-2.99) and 1.50 (1. 00-2.38), p < 0.001, respectively. Our study demonstrated that NIDDM p atients with and without albuminuria had increased transcapillary esca pe of albumin and raised prorenin activity, whereas only those with al buminuria had increased von Willebrand factor. Patients with NIDDM may have abnormal endothelial function in the absence of albuminuria.