Abstract
To elucidate the relation between the nonenzymatic glucosylation of the glomerular basement membrane and diabetic functional nephropathy, the daily urinary excretions of glucosylated albumin (GA) as well as serum GA levels were estimated in 21 normal subjects, 12 patients with nephrotic syndrome, and 36 patients with diabetes mellitus. The diabetics were divided into three groups according to their daily urinary excretion of albumin: Group A (<150 mg), group B (150-1000 mg), and Group C (>1000 mg). Urinary albumin was purified with affinity chromatography, and GA was determined by the thiobarbituric acid method after acid hydrolysis of the protein. The Mean ± SD serum glucosylated albumin (SGA) concentration in normal subjects was 0.33±0.04 nmol 5-HMF/mg albumin. In the diabetics, SGA concentrations were significantly higher than in normal subjects, reflecting the elevation of blood glucose levels. On the other hand, the mean uinary glucosylated albumin (UGA) in normal subjects was 2.4±1.6 nmol 5-HMF/mg albumin, which was significantly higher than those in the diabetics and the patients with nephrotic syndomc. Moreover, the UGA tended to decrease in the patients with elevated serum creatinine levels.
The mean UGA/SGA ratio in normal subjects was 7. 7 ± 4.4, indicating that GA was selectively excreted in the urine. It was remarkable that the ratio declined to 2.4±1.6 in group A, in which urinary protein was not quantitatively detection in repeated examinations, probably because of the charge selectivity defect due to the glucosylation of the glomerular basement membrane. In groupC and the patients with nephrotic syndrome, the ratio was around 1, indicating that the pore size defect in the basement membrane is present in these patients.
Although no correlation was found between the ratio and the duration of the disease, a significantly inverse correlation was found between SGA and the ratio in group A. Moreover, in a patient with insulin-dependent diabetes mellitus, whose SGA and UGA were determined within about three months after the onset of the disease, the ratio was markedly diminished.
It is concluded that the selectivity towards UGA is damaged in functional diabetic nephropathy and that the control of the blood glucose level is important to prevent the initial events in diabetic nephropathy.
