Increased basic fibroblast growth factor-like substance in plasma from a subset of middle-aged or elderly male diabetic patients with microalbuminuria or proteinuria

Basic fibroblast growth factor (bFGF) is a potent endothelial cell growth factor that does not normally circulate in healthy nonpregnant adults. bFGF has been reported in plasma from patients with certain tumors consistent with a postulated role in tumor angiogenesis. In the present study we used an endothelial cell bioassay to test for a bFGF like substance in plasma and urine from patients with noninsulin-dependent diabetes mellitus. We found increased bFGF immunoreactivity that correlated with bFGF-like endothelial cell growth-promoting activity in plasma from a subset of diabetic patients with persistent microalbuminuria or overt proteinuria. Plasma (bFGF-like) growth-promoting activity was significantly correlated with glycosylated hemoglobin (P < 0.05), but not patient age, race, degree of proteinuria, or systolic blood pressure. In a group of microalbuminuric or proteinuric diabetic subjects well matched according to baseline clinical characteristics, plasma (bFGF-like) growth-promoting activity was significantly decreased (P < 0.0001) in the subgroup of patients who were being treated with an angiotensin-converting enzyme inhibitor simultaneous to blood drawing for plasma growth assay. In patients not treated with an angiotensin-converting enzyme inhibitor, multiple regression analysis showed that retinopathy was the only variable significantly associated with plasma growth-promoting activity. These results imply that plasma bFGF endothelial cell growth-promoting activity is increased and may contribute to pathophysiology in a heterogeneous subset of noninsulin-dependent diabetes mellitus patients with persistent microalbuminuria or overt proteinuria.