Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study.
OBJECTIVE
Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP).


METHODS
We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-β (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study.


RESULTS
Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-β (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP.


CONCLUSIONS
Isolated hyperglycemia is associated with higher serum concentrations of TGF-β, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined.
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. Electronic address: Isha_Agarwal@hms.harvard.edu.
Isha
I
Agarwal
Department of Medicine, Boston University, Boston, MA, USA.
Nicole L
NL
Glazer
Department of Research and Education, St. Francis Hospital, The Heart Center, Roslyn, NY, USA; SUNY at Stony Brook, Stony Brook, NY, USA.
Eddy
E
Barasch
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Luc
L
Djousse
Department of Medicine, University of Maryland Medical School, Baltimore, MD, USA.
John S
JS
Gottdiener
Department of Medicine, University of California San Diego, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Joachim H
JH
Ix
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Jorge R
JR
Kizer
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Eric B
EB
Rimm
The New York Academy of Medicine, New York, NY, USA; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA; Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
David S
DS
Siscovick
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.
George L
GL
King
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Ken J
KJ
Mukamal
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005355:Fibrosis / Q000097:blood; D006262:Health; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; C041876:procollagen Type III-N-terminal peptide
Fibrosis; Growth factors; Hyperglycemia; Insulin resistance