HHS Public Access Author manuscript Author Manuscript
Metabolism. Author manuscript; available in PMC 2016 October 01. Published in final edited form as: Metabolism. 2015 October ; 64(10): 1316–1323. doi:10.1016/j.metabol.2015.07.013.
Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study Isha Agarwal, AB/AMa, Nicole L. Glazer, PhDb, Eddy Barasch, MDc, Luc Djousse, MD DScd, John S. Gottdiener, MDe, Joachim H. Ix, MD MASf, Jorge R. Kizer, MD MScg, Eric B. Rimm, SDa,h, David S. Siscovick, MD MPHi, George L. King, MDj, and Ken J. Mukamal, MD MPHk aDepartments
Author Manuscript
bDepartment
of Epidemiology and Nutrition, Harvard School of Public Health, MA, USA
of Medicine, Boston University, MA, USA
cDepartment
of Research and Education, St. Francis Hopsital, The Heart Center, SUNY at Stonybrook, NY, USA dDepartment
of Medicine, Brigham and Women’s Hospital, MA, USA
eDepartment
of Medicine, University of Maryland Medical School, MD, USA
fDepartment
of Medicine, University of California San Diego and Veterans Affairs San Diego Healthcare System, CA, USA gDepartments
of Medicine, Epidemiology, and Population Health, Albert Einstein College of Medicine, NY, USA
Author Manuscript
hChanning
Division of Network Medicine, Brigham and Women's Hospital, MA, USA
iThe
New York Academy of Medicine, New York, NY, USA, and Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, WA, USA
jResearch
Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School,
MA, USA kDepartment
of Medicine, Beth Israel Deaconess Medical Center, MA, USA
Abstract Aim—Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated
Author Manuscript
Corresponding author: Isha Agarwal, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston MA 02115, Fax: 617.566.7805, Phone: 617.432.1050, [email protected]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement There are no conflicts of interest to disclose. Author contributions I.A. and K.J.M. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. I.A. wrote the manuscript. N.L.G., E.B., M.L.B., L.D., A.L.F., J.S.D., J.H.I., J.R.K., E.B.R., D.S.S., R.P.T, G.L.K, and K.J.M. reviewed and edited the manuscript.
Agarwal et al.
Page 2
Author Manuscript
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 = 1,559) and PIIINP (n = 3,024) 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
Metabolism. Author manuscript; available in PMC 2016 October 01. Published in final edited form as: Metabolism. 2015 October ; 64(10): 1316–1323. doi:10.1016/j.metabol.2015.07.013.
Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study Isha Agarwal, AB/AMa, Nicole L. Glazer, PhDb, Eddy Barasch, MDc, Luc Djousse, MD DScd, John S. Gottdiener, MDe, Joachim H. Ix, MD MASf, Jorge R. Kizer, MD MScg, Eric B. Rimm, SDa,h, David S. Siscovick, MD MPHi, George L. King, MDj, and Ken J. Mukamal, MD MPHk aDepartments
Author Manuscript
bDepartment
of Epidemiology and Nutrition, Harvard School of Public Health, MA, USA
of Medicine, Boston University, MA, USA
cDepartment
of Research and Education, St. Francis Hopsital, The Heart Center, SUNY at Stonybrook, NY, USA dDepartment
of Medicine, Brigham and Women’s Hospital, MA, USA
eDepartment
of Medicine, University of Maryland Medical School, MD, USA
fDepartment
of Medicine, University of California San Diego and Veterans Affairs San Diego Healthcare System, CA, USA gDepartments
of Medicine, Epidemiology, and Population Health, Albert Einstein College of Medicine, NY, USA
Author Manuscript
hChanning
Division of Network Medicine, Brigham and Women's Hospital, MA, USA
iThe
New York Academy of Medicine, New York, NY, USA, and Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, WA, USA
jResearch
Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School,
MA, USA kDepartment
of Medicine, Beth Israel Deaconess Medical Center, MA, USA
Abstract Aim—Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated
Author Manuscript
Corresponding author: Isha Agarwal, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston MA 02115, Fax: 617.566.7805, Phone: 617.432.1050, [email protected]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement There are no conflicts of interest to disclose. Author contributions I.A. and K.J.M. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. I.A. wrote the manuscript. N.L.G., E.B., M.L.B., L.D., A.L.F., J.S.D., J.H.I., J.R.K., E.B.R., D.S.S., R.P.T, G.L.K, and K.J.M. reviewed and edited the manuscript.
Agarwal et al.
Page 2
Author Manuscript
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 = 1,559) and PIIINP (n = 3,024) 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
