Circulating Progenitor Cell Count Predicts Microvascular Outcomes in Type 2 Diabetic Patients

Context: Diabetes reduces the levels of circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs), which promote vascular repair and are inversely correlated with cardiovascular risk. Objective: The objective of the study was to test whether CPC/EPC levels predict onset/progression of microangiopathy in a cohort of type 2 diabetic (T2D) patients. Design: This was a pseudoprospective study with a 3.9-year follow-up. Setting: The study was conducted at a tertial referral diabetes outpatient clinic. Patients: A total of 187 T2D patients having a baseline determination of CPCs/EPCs participated in the study. Intervention: Baseline data on demographics, anthropometrics, concomitant risk factors, diabetic complications, and medications were collected. Main Outcome Measure: Onset or progression of microangiopathy was assessed at follow-up compared with baseline. Results: New onset or progression of microalbuminuria, chronic kidney disease, retinopathy, and neuropathy occurred in 70 patients (9.5%/y). After controlling the false discovery rate, baseline CD34(+) CPCs and EPCs were significantly lower in patients with onset/progression of microalbuminuria and any microangiopathy. Patients with baseline CD34(+) CPC or CD133(+)/kinase insert domain-containing receptor(+)/EPC levels below the median were more likely to experience worsening microangiopathy than those with high cell levels. Independently from confounders, including age, sex, glycated hemoglobin, and diabetes duration, CD34(+) cells predicted onset/progression of microalbuminuria, retinopathy, and any microangiopathy in false discovery rate-adjusted analyses. A low CD34(+) cell count limited the beneficial effects of renin-angiotensin system blockers on microalbuminuria progression. Conclusions: Levels of circulating (endothelial) progenitor cells predict microvascular outcomes in T2D. Together with previous studies showing an association with cardiovascular events, these data indicate that CPCs/EPCs represent biomarkers of the global complication burden in diabetes.