Higher fasting glucose levels are associated with reduced circulating angiogenic cell migratory capacity among healthy individuals

Abstract

Background: Chronic or severe acute elevations in plasma glucose are associated with decreases in the number and function of circulating angiogenic cells (CACs). However, less is known about whether fasting plasma glucose levels (FPG) within the normal or pre-diabetic range among healthy individuals are associated with decreased CAC function. Establishing this relationship is an important step in developing a line of research that may ultimately lead to preventative lifestyle interventions intended to maximize endogenous CAC function and reduce cardiometabolic disease risk.

Objectives: 1) To examine whether increases in FPG are associated with decreases in CAC migration among healthy individuals with FPG levels below the threshold for hyperglycemia, and 2) to contrast effect of FPG on CAC migration toward a pro-angiogenic stimulus (vascular endothelial growth factor; VEGF) with effect on intrinsic cell migratory capacity (i.e., random migration with no stimulus).

Methods: 28 men and women ranging from 20-57 years of age and free of cardiovascular disease participated in a pilot study, involving a fasting blood draw for FPG and isolation of peripheral blood mononuclear cells. CAC migration toward VEGF and random cell migration (control) were assessed in vitro. VEGF-induced migration that was normalized to control migration, representing the VEGF-response component of chemotaxis independent of motility, was calculated to determine whether any impairment in migration to VEGF was due to lower specific response to VEGF or to lower non-specific migratory capacity.

Results: Increased levels of FPG were associated in a dose-response fashion with a significantly lower random migration under control conditions (CTRL: r= -.408, p=.031), no differences in migration to VEGF (r= -.039, p=.842) and a borderline association with VEGF-induced migration normalized to control migration (VEGF/CTRL: r=.349, p=.069). The relationship between FPG and random migration under control conditions remained significant when controlling for gender and body mass index (p's<.05), and became borderline significant when controlling for age (p=.062).

Conclusions: Among healthy individuals, higher fasting glucose levels, despite falling below the diabetic range, are associated with decreased random CAC migration. These findings suggest a need for further studies investigating the effects of lifestyle or dietary interventions on glucose regulation and CAC function.

Keywords: Impaired fasting glucose; angiogenesis; cardiovascular; chemokinesis; chemotaxis; circulating angiogenic cells (CACs); endothelial progenitor cells (EPCs); metabolism; migration; motility; pre-diabetic.

Figure 1

Scatterplot of the association between fasting plasma glucose and CAC migration to a control stimulus among healthy individuals. This relationship was significant (r= -.408, p=.031) among 28 healthy individuals free of cardiovascular disease with fasting glucose levels below the threshold for hyperglycemia, using a critical alpha of .05.