Glomerulopathy in spontaneously diabetic rat. Impact of glycemic control.

The spontaneously diabetic BioBreeding/Worcester (BB/W) rat was used to examine the role of glycemic control in the pathogenesis of diabetic glomerulopathy and proteinuria. Nondiabetic BB/W rats (group 1) were compared with moderately (group 2) and severely (group 3) hyperglycemic diabetic animals of similar age. Urinary protein excretion and morphometric measurements of glomerular basement membrane (GBM) width and mesangial area were performed after 4, 8, and 12 mo of study. At 4 mo, urinary protein excretion both in group 2 (9.3 +/- 0.7 mg/24 h) and group 3 (24.8 +/- 1.98 mg/24 h) exceeded that in group 1 (5.4 +/- 0.6 mg/24 h; P less than .05). Moreover, proteinuria in group 3 was significantly greater than in group 2 (P less than .05). In addition, proteinuria increased in group 3 animals between 4 and 12 mo of study but did not advance in groups 1 or 2. GBM width in both diabetic groups (168.8 +/- 2.4 and 165.7 +/- 2.2 nm, groups 2 and 3, respectively) exceeded that in group 1 (148.3 +/- 3.8 nm; P less than .01) by 4 mo. At 12 mo, severely hyperglycemic group 3 animals had significantly greater GBM thickening than group 2. GBM width increased in all three groups over the course of study, but the rate of growth did not differ between groups 1 and 2. However, the rate of growth in group 3 was greater than in either group 1 or group 2. Urinary protein excretion correlated significantly with GBM width in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)