Abstract 9292: Can Endothelial Progenitor Cell Dysfunction in Patients with Uncontrolled Diabetes be Normalized by Tight Glycemic Control?

Background: Recent evidence has shown that endothelial progenitor cells (EPCs) have an important role in repair process following vascular injury, and that in patients (pts) with diabetes EPCs number and function are reduced. Small studies suggest that tight metabolic control may improve the properties of EPCs in pts with uncontrolled diabetes. However, it is unclear whether following such intensive control EPC properties approach the levels of subjects without diabetes. We, therefore, aimed to examine whether after intensive glycemic control EPCs number and function are similar to the EPC profile in non-diabetics. Methods: Twenty five pts with treated diabetes who underwent intensive glycemic control for a period of 3-4 months (initial HgA1C > 8.5%; HgA1c goal < 7%) were compared to 25 matched non-diabetic subjects. The proportion of peripheral mononuclear cells (PMNCs) expressing VEGFR-2, CD133 and CD34 were evaluated by flow cytometry. EPCs colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. Functional properties of the cultured cells were evaluated by the MTT viability assay, and migration - modified Boyden assay. Results: The two groups (n=25 each) were well-matched: mean age 59.5-61.5 years, 20% women and BMI of 29-31. All pts were treated with aspirin and statins. At baseline pts with diabetes had significantly lower levels of circulating EPCs and reduced functional properties compared with the non-diabetic subjects. After the tight control period HgA1C decreased from 9.5% to 8%, and circulating EPCs increased to a level similar to the non-diabetic group (VEGFR-2 + CD34 + : 1.12±0.15% vs. 1.14±0.14%; VEGFR-2 + CD133 + : 0.66±0.11% vs. 0.72±0.11%, respectively). However, the number of EPC CFUs in the diabetes group after the control period remained lower compared to the non-diabetes group (10.96±1.71 vs. 15.4±1.9 colonies per well, respectively, P=0.001). Furthermore, the MTT viability test and migration were also reduced in the diabetic compared with the non-diabetic group. Conclusions: Following a period of tight glycemic control in pts with diabetes numbers of circulating EPCs increase to a level similar to that of subjects without diabetes, but their functional properties remain attenuated.