title: Reduced circulating stem cells associate with excess fasting and post-load NEFA exposure in healthy adults with normal glucose tolerance.
abstract: Reduced levels of circulating stem cells (CSCs) predict cardiovascular events and death, but the factors underlying variability of CSCs in healthy adults are mostly unknown. Previous studies detected associations of CSCs with glucose tolerance or insulin resistance, while the role of fatty acids has been overlooked. We herein aimed to describe in better detail the metabolic abnormalities associated with a reduced CSC level.
  
  
  
  This was a cross-sectional study on 94 healthy male and female individuals with normal glucose tolerance, aged 18-65 years. All participants underwent an oral glucose tolerance test (OGTT) with blood samples collected at 0, 10, 20, 30, 60, 90 and 120 min. Mathematical models were applied to plasma glucose, insulin, C-peptide and non-esterified fatty acids (NEFA) concentrations. CSCs were defined as CD34+or CD133+.
  
  
  
  Participants (mean ± SEM age 43.8 ± 0.7; 41% males) were divided according to CSC levels below (low) or above (high) the median value and metabolic parameters were compared. There was no significant baseline difference between groups except for higher concentrations of fasting NEFA in subjects with low CSCs. Upon OGTT, individuals with low CSCs had higher area under curve (AUC) of NEFA (p < 0.001) and no significant differences in glucose, insulin and C-peptide. Several insulin sensitivity and beta cell function indexes were not significantly different, except for a decrease in the disposition index (DI) in subjects with low CSCs. CSCs were associated with excess NEFA levels independently from age and DI.
  
  
  
  We show for the first time that, in healthy adults with normal glucose tolerance, low CSCs are strongly associated with excess NEFA exposure. The pathophysiological consequence of this association needs to be interpreted in view of the prognostic role of CSCs. Future studies should explore whether excess NEFA and low CSCs and are causally interconnected.
authors.affiliation: Department of Medicine, University of Padova, 35128 Padova, Italy. Electronic address: gianpaolo.fadini@unipd.it.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Metabolic Unit, CNR Institute of Neuroscience, 35127 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.affiliation: Metabolic Unit, CNR Institute of Neuroscience, 35127 Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Department of Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: Department of Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Saula
authors.initials: S
authors.lastname: Vigili de Kreutzenberg
mesh_terms: D000071916:AC133 Antigen / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D018952:Antigens, CD34; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C000606023:PROM1 protein, human
keywords: Beta cell function; Bone marrow; Fat; Insulin resistance; Regeneration