Title | Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Agarwal, I, Glazer, NL, Barasch, E, Djoussé, L, Gottdiener, JS, Ix, JH, Kizer, JR, Rimm, EB, Siscovick, DS, King, GL, Mukamal, KJ |
Journal | Metabolism |
Volume | 64 |
Issue | 10 |
Pagination | 1316-23 |
Date Published | 2015 Oct |
ISSN | 1532-8600 |
Keywords | Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Cardiovascular System, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Fatty Acids, Nonesterified, Female, Fibrosis, Health, Humans, Insulin, Insulin Resistance, Male, Metabolic Diseases, Peptide Fragments, Procollagen, Transforming Growth Factor beta |
Abstract | <p><b>AIM: </b>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).</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
DOI | 10.1016/j.metabol.2015.07.013 |
Alternate Journal | Metab. Clin. Exp. |
PubMed ID | 26282733 |
PubMed Central ID | PMC4939831 |
Grant List | 268200800007C / / PHS HHS / United States 268201200036C / / PHS HHS / United States AG023629 / AG / NIA NIH HHS / United States F30 HL118775 / HL / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL094555 / HL / NHLBI NIH HHS / United States HL118775 / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL094555 / HL / NHLBI NIH HHS / United States |