Gian Paolo Fadini1, Andrea Tura2, Giovanni Pacini2, Angelo Avogaro3, Saula Vigili de Kreutzenberg3. 1. Department of Medicine, University of Padova, 35128 Padova, Italy. Electronic address: gianpaolo.fadini@unipd.it. 2. Metabolic Unit, CNR Institute of Neuroscience, 35127 Padova, Italy. 3. Department of Medicine, University of Padova, 35128 Padova, Italy.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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+. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: 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+. RESULTS: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. CONCLUSIONS: 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.