Depletion of Circulating CD34+/KDR+ Cells in Type 2 Diabetes is Associated With Glycemic Control

Document Type



Internal Medicine (East Africa); Brain and Mind Institute


Background and Hypothesis: Circulating levels of endothelial progenitor cells have been found to be predictive of cardiovascular events and mortality. Although the levels of these cells reflect overall cardiovascular disease (CVD) risk, studies assessing their association with major CVD factors - hypertension, dyslipidemia and diabetes have yielded inconsistent results and the mechanisms contributing to EPC depletion remain unknown. We hypothesized that EPC depletion occurring in diabetes is mediated in part by hyperglycemia or insulin resistance.

Methods: Circulating levels of progenitor cells were measured by flow cytometry in 108 diabetic or non-diabetic subjects recruited from the University of Louisville Health System. Reactive hyperemia index (RHI) was measured by the EndoPAT. Demographic information was acquired and blood, plasma and urine were used for biochemical analyses. Subjects were divided into high and low EPC count groups using the median split. Data was analyzed using a Chi-square test, a two-sample rank sum test, and univariable and multivariable logistic regressions.

Results: Levels of CD34+/KDR+/CD14−/CD16− cells (EPCs) were associated with the diagnosis of diabetes (p=0.04), but not with other demographic covariates, hypertension or dyslipidemia. Levels of CD34+, AC133+ and CD34+/AC133+/CD45+ cells also displayed significant association with diabetes (p=0.038, 0.014 and 0.038 respectively). RHI was strongly associated with diabetes (p<0.0001) hypertension and dyslipidemia, however, no significant associations were observed between RHI and EPCs. EPC levels were inversely associated with HbA1C (p=0.047) and fasting blood glucose, but not with insulin levels or the HOMA-IR score. In the complete model, the association between EPCs and diabetes was strengthened by the inclusion of RHI, indicating more robust EPC depletion in those with endothelial dysfunction.

Conclusion: Circulating EPC levels are a robust index of long-term glycemic control and are associated with hyperglycemia rather than contemporaneous insulin levels or endothelial dysfunction. These findings may help in prognosis and early identification of CVD risk in patients with diabetes, independent of other risk estimates.


This work was published before the author joined Aga Khan University.