Characterization of circulating and endothelial progenitor cells in patients with extreme-duration type 1 diabetes.
OBJECTIVE
We characterized and correlated endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) with lack of vascular complications in the Joslin Medalist Study in patients with type 1 diabetes for 50 years or longer.


METHODS
EPC and CPC levels were ascertained by flow cytometry and compared among Medalists (n = 172) with or without diabetic retinopathy (DR; n = 84 of 162), neuropathy (n = 94 of 165), diabetic nephropathy (DN; n = 18 of 172), cardiovascular disease (CVD; n = 63 of 168), age-matched controls (n = 83), type 2 diabetic patients (n = 36), and younger type 1 diabetic patients (n = 31). Mitogens, inflammatory cytokines, and oxidative markers were measured in blood or urine. Migration of cultured peripheral blood mononuclear cells (PBMCs) from Medalists and age-matched controls were compared.


RESULTS
Medalists' EPC and CPC levels equaled those of their nondiabetic age-matched controls, were 10% higher than those in younger type 1 diabetic patients, and were 20% higher than those in age-matched type 2 diabetic patients. CPC levels were 15% higher in Medalists without CVD and nephropathy than in those affected, whereas EPC levels were significantly higher in those without peripheral vascular disease (PVD) than those with PVD. Stromal-derived factor 1 (SDF-1) levels were higher in Medalists with CVD, DN, and DR than in those not affected and their controls. IGF-I levels were lower in Medalists and correlated inversely with CPC levels. Additionally, cultured PBMCs from Medalists migrated more than those from nondiabetic controls.


CONCLUSIONS
Normal levels of EPC and CPC in the Medalists, unlike other groups with diabetes, especially those without CVD, support the idea that endogenous factors exist to neutralize the adverse effects of metabolic abnormalities of diabetes on vascular tissues.
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Sonia L
SL
Hernandez
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MADepartment of Internal Medicine, Harvard Medical School, Boston, MA.
Jennifer H
JH
Gong
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MATianjin Medical University, Tianjin, China.
Liming
L
Chen
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
I-Hsien
IH
Wu
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MABeetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, Boston, MADepartment of Ophthalmology, Harvard Medical School, Boston, MA.
Jennifer K
JK
Sun
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MADepartment of Internal Medicine, Harvard Medical School, Boston, MA.
Hillary A
HA
Keenan
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA george.king@joslin.harvard.edu.
George L
GL
King
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood; D003930:Diabetic Retinopathy / Q000150:complications; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000175:diagnosis; D055815:Young Adult
D015415:Biomarkers