title: Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF).
abstract: Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.
authors.affiliation: Department of Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Brausewetter
authors.forename: P M
authors.initials: PM
authors.lastname: Jehle
authors.forename: M F
authors.initials: MF
authors.lastname: Jung
authors.forename: B O
authors.initials: BO
authors.lastname: Boehm
authors.forename: J
authors.initials: J
authors.lastname: Brueckel
authors.forename: V
authors.initials: V
authors.lastname: Hombach
authors.forename: H H
authors.initials: HH
authors.lastname: Osterhues
mesh_terms: D000328:Adult; D000368:Aged; D002199:Capillary Permeability; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D018972:Insulin-Like Growth Factor Binding Protein 3; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I