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Both Vascular Endothelial Growth Factor and Soluble Flt-1 Are Increased in Type 2 Diabetes But Not in Impaired Fasting Glucose
  1. Debashis Nandy, MD*,
  2. Debabrata Mukhopadhyay, PhD,
  3. Ananda Basu, MD*
  1. From the *Division of Endocrinology and Metabolism and †Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN.
  1. Received April 16, 2010, and in revised form May 18, 2010.
  2. Accepted for publication May 21, 2010.
  3. Reprints: Ananda Basu, MD, Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905. E-mail: basu.ananda{at}mayo.edu.
  4. This work was carried out with the support of NIH grants HL072178 and HL070567 to D.M. and Mayo Foundation Clinical Research award to A.B. Support from the General Clinical Research Center of Mayo Clinic College of Medicine and study volunteers is also acknowledged.

Abstract

Objective Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis.

Research Design We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 ± 2.1 years; body mass index [BMI], 26.1 ± 0.9 kg/m2; glucose, 5.0 ± 0.1 mM), 15 IFG (aged 52.9 ± 1.8 years; BMI, 32.7 ± 1.3 kg/m2; glucose, 6.4 ± 0.1 mM), and 8 DM (aged 55.8 ± 3.2 years; BMI, 30.0 ± 1.0 kg/m2; glucose, 9.3 ± 0.5 mM) subjects.

Results Plasma VEGF (42.1 ± 4.0 vs 24.2 ± 0.9 vs 29.4 ± 3.8 pg/mL, respectively) and sFlt-1 (119.4 ± 4.9 vs 58.9 ± 3.2 vs 56.7 ± 1.2 pg/mL, respectively) concentrations were higher (P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower (P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects.

Conclusions Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations.

Key Words
  • VEGF
  • sFlt-1
  • diabetes

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