Disclosure: The authors declared no conflict of interest.
Article first published online: 20 JUN 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 5, pages 1031–1038, May 2013
How to Cite
Kavanagh, K., Espeland, M. A., Sutton-Tyrrell, K., Barinas-Mitchell, E., Khoudary, S. R. E. and Wildman, R. P. (2013), Liver fat and SHBG affect insulin resistance in midlife women: The Study of Women's Health Across the Nation (SWAN). Obesity, 21: 1031–1038. doi: 10.1002/oby.20077
Funding agencies: Kavanagh is supported by K01AG 033641. The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The SWAN Heart Study was supported by the National Heart, Lung, and Blood Institute (Grants HL065581 and HL065591). The Chicago site of the SWAN Heart Study is also supported by the Charles J. and Margaret Roberts Trust.
- Issue published online: 20 JUN 2013
- Article first published online: 20 JUN 2013
- Accepted manuscript online: 18 OCT 2012 12:59PM EST
- Manuscript Accepted: 3 SEP 2012
- Manuscript Revised: 18 JUN 2012
- Manuscript Received: 7 DEC 2011
- Women's Health Across the Nation (SWAN). Grant Number: K01AG 033641
- National Institutes of Health (NIH)
- National Institute on Aging (NIA)
- National Institute of Nursing Research (NINR)
- NIH Office of Research on Women's Health (ORWH). Grant Numbers: NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495
- SWAN Heart Study
- National Heart, Lung, and Blood Institute. Grant Numbers: HL065581, HL065591
The liver is an insulin-responsive organ that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormone binding globulin (SHBG). Our objective was to explore whether lower SHBG was associated with ectopic liver fat and mediated its effect on insulin resistance in The Study of Women's Health Across the Nation (SWAN).
Design and Methods:
A subset of midlife African American and Caucasian women from SWAN (n = 208; 50.9 ± 0.18 yrs; 71% Caucasian) had computed tomography scans to quantify visceral, subcutaneous and liver fat. Blood samples were collected and assayed for hormonal and metabolic markers.
The cohort, while overweight, was generally healthy, and both liver fat and SHBG were unaffected by menopausal stage or race. Both higher liver fat and lower SHBG levels were significantly associated with higher insulin concentrations after adjustment for adiposity (r = −0.25, P < 0.001 and r = −0.18, P = 0.01). SHBG and liver fat had additive effects on insulin concentrations such that women with the lowest SHBG and the highest fat levels had the highest values (interaction P = 0.09). The association between SHBG and insulin was more apparent among women with fattier livers. SHBG and liver fat appear to have independent effects on insulin levels as adjustment for each other did not diminish the strength of either association (P = 0.023 and 0.001 respectively).
These results confirmed the strong independent associations between increased liver fat and decreased SHBG with increased metabolic risk in midlife women. Further these data underscore the need for additional research into the role of liver fat in modifying SHBG's influence on insulin levels.