Mauro Rigato1, Cristina Bittante1, Mattia Albiero1, Angelo Avogaro1, Gian Paolo Fadini1. 1. Division of Metabolic Diseases, Department of Medicine (M.R., C.B., M.A., A.A., G.P.F.), University of Padova, 35128 Padova, Italy; and Venetian Institute of Molecular Medicine (A.A., G.P.F.), 35128 Padova, Italy.
Abstract
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.
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 diabetesoutpatient 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.
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