Depletion of circulating progenitor cells precedes overt diabetes: a substudy from the VA enhanced fitness trial.
BACKGROUND
One theory of aging and disease development is that chronic injury (pathology) results in activation of regenerative processes and initial repair, with overt disease arising only after exhaustion of reparative capability leads to inadequate repair. While depletion of circulating progenitor cells (CPCs) has been noted in diabetes, the degree to which CPC depletion predates and is associated with propensity to develop overt disease is unclear.


METHODS
The Enhanced Fitness trial enrolled overweight/obese (body mass index >25) sedentary patients with glucose intolerance but without overt diabetes. Baseline CPCs were measured in 129 patients based on the cell surface markers CD34, CD133, and aldehyde dehydrogenase (ALDH) activity. HgbA1C, fasting insulin and glucose levels, and HOMA calculations were ascertained.


RESULTS
Lower counts of early angiogenic CPCs identified as CD34(+), CD34(+)CD133(+), and ALDH-bright (ALDH(br)) cells were associated with impairments in glucose homeostasis as reflected by HgbA1C, but not fasting insulin, glucose, or HOMA-IR. These associations remained when corrected for age and cardiovascular risk factors.


CONCLUSIONS
The numbers of CD34(+) and ALDH(br) CPCs were significantly lower in patients with impaired glucose tolerance. Depletion of reparative capacity as reflected by loss of CPCs may presage overt disease as exemplified in this pre-diabetes model.
Duke Clinical Research Institute, Duke University Health Care System, Durham, NC, USA; Department of Medicine, Duke University Health Care System, Durham, NC, USA; Claude D. Pepper OAIC, Duke University Health Care System, Durham, NC, USA. Electronic address: thomas.povsic@duke.edu.
Thomas J
TJ
Povsic
Richard
R
Sloane
Jennifer B
JB
Green
Jiying
J
Zhou
Carl F
CF
Pieper
Megan P
MP
Pearson
Eric D
ED
Peterson
Harvey J
HJ
Cohen
Miriam C
MC
Morey
D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D018952:Antigens, CD34 / Q000378:metabolism; D001772:Blood Cell Count; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018149:Glucose Intolerance / Q000097:blood* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010809:Physical Fitness; D011236:Prediabetic State / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D050697:Retinal Dehydrogenase / Q000378:metabolism; D014728:Veterans
D018952:Antigens, CD34; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
Disease progression; Etiology; Pathophysiology; Prediabetes; Progenitor cells; Stem cells