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Increased Levels of Serum Fibroblast Growth Factor-2 in Diabetic Pregnant Women with Retinopathy¹

Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph’s Health Center (D.J.H., E.A.), London, Ontario, Canada N6A 4V2; the Departments of Medicine (D.J.H., E.A.), Pediatrics (D.J.H.), and Physiology (D.J.H.), University of Western Ontario, London, Ontario, Canada N6A 5O5; the Institute of Experimental Clinical Research, Aarhus Kommunehospital (A.F.), DK-8000 Aarhus C., Denmark; and the Gynecological and Obstetrical Department, Skejby University Hospital (F.F.L., J.G.K.), DK-8200 Aarhus N., Denmark

Address all correspondence and requests for reprints to: Dr. D. J. Hill, Lawson Research Institute, St. Joseph’s Health Center, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2. E-mail: dhill{at}lri.stjosephs.london.on.ca

Fibroblast growth factor-2 (FGF-2) is a potent mitogen and angiogenic factor normally absent from the adult circulation. We have previously shown that it appears in normal maternal serum and that circulating FGF-2 levels are elevated in pregnancies complicated by diabetes. This study was performed to determine whether serum FGF-2 is more abundant in pregnant diabetic women with retinopathy than in those without. Serum was collected monthly between 14–30 weeks gestation and every 2 weeks from then until delivery (35–38 weeks) from 36 women with type 1 diabetes. FGF-2 was extracted by heparin-Sepharose affinity chromatography and quantified by specific RIA. Patients were divided according to the White classification of diabetes. In 17 women without retinopathy (White groups B, C, and D₀), immunoreactive FGF-2 was detectable at 14 weeks (mean ± SEM, 154 ± 39 pmol/L), was maximal after 26 weeks (306 ± 38 pmol/L), after which values steadily declined to term (212 ± 48 pmol/L). In 19 women with simplex or proliferative retinopathy (White groups D₊ and R), circulating levels of FGF-2 were significantly greater between 22–32 weeks gestation (22 weeks, 480 ± 102 vs. 239 ± 38 pmol/L; P < 0.05). Serum FGF-2 was significantly correlated with hemoglobin A_1c levels at 22, 30, and 34 weeks gestation. The mean birth weight of the infants did not significantly differ between groups. Macroalbuminuria was absent in all patients, and creatinine clearance and blood pressure did not significantly differ between the two groups. The results suggest that serum FGF-2 is substantially elevated in pregnant diabetic women with retinopathy in second and early third trimesters. It is unlikely that in these patients this was primarily due to altered FGF-2 clearance, but may relate to excessive production by the utero-placental compartment. The high circulating levels of FGF-2 may be causally related to the development of diabetic retinopathy.

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