TY - JOUR T1 - Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study. JF - Metabolism Y1 - 2015 A1 - Agarwal, Isha A1 - Glazer, Nicole L A1 - Barasch, Eddy A1 - Djoussé, Luc A1 - Gottdiener, John S A1 - Ix, Joachim H A1 - Kizer, Jorge R A1 - Rimm, Eric B A1 - Siscovick, David S A1 - King, George L A1 - Mukamal, Ken J KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Blood Glucose KW - Cardiovascular System KW - Cross-Sectional Studies KW - Diabetes Complications KW - Diabetes Mellitus KW - Fatty Acids, Nonesterified KW - Female KW - Fibrosis KW - Health KW - Humans KW - Insulin KW - Insulin Resistance KW - Male KW - Metabolic Diseases KW - Peptide Fragments KW - Procollagen KW - Transforming Growth Factor beta AB -

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 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.

VL - 64 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26282733?dopt=Abstract ER -