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


METHODS
This was a pseudoprospective study with a 3.9-year follow-up.


METHODS
The study was conducted at a tertial referral diabetes outpatient clinic.


METHODS
A total of 187 T2D patients having a baseline determination of CPCs/EPCs participated in the study.


METHODS
Baseline data on demographics, anthropometrics, concomitant risk factors, diabetic complications, and medications were collected.


METHODS
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.
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.
Mauro
M
Rigato
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.
Cristina
C
Bittante
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.
Mattia
M
Albiero
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.
Angelo
A
Avogaro
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.
Gian Paolo
GP
Fadini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000473:pathology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis*; D018450:Disease Progression; D066026:Endothelial Progenitor Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis