Fatty Liver Is Associated With Dyslipidemia and Dysglycemia ... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Fatty Liver Is Associated With Dyslipidemia and Dysglycemia Independent of Visceral Fat: the Framingham Heart Study

Speliotes, Elizabeth K.1,5,*; Massaro, Joseph M.6,7; Hoffmann, Udo2; Vasan, Ramachandran S.6,8; Meigs, James B.4; Sahani, Dushyant V.2; Hirschhorn, Joel N.5,10,11; O'Donnell, Christopher J.3,6; Fox, Caroline S.6,9

1_Departments of Gastroenterology, Massachusetts General Hospital, Boston MA_

2_Radiology, Massachusetts General Hospital, Boston MA_

3_Cardiology, Massachusetts General Hospital, Boston MA_

4_General Medicine, Massachusetts General Hospital, Boston MA_

5_Department of Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA_

6_National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, MA_

7_Department of Biostatistics, Boston University, Boston, MA_

8_Departments of Cardiology, Preventive Medicine, and Medicine, Boston University School of Medicine, Boston, MA_

9_Departments of Medicine and Endocrinology, Brigham and Women's Hospital, Boston, MA_

10_Departments of Endocrinology and Genetics, Children's Hospital, Boston, MA_

11_Department of Genetics, Harvard Medical School, Boston, MA_

*Address reprint requests to: Department of Gastroenterology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. Email:[email protected]; fax: 617-724-1685

Received 20 July 2009; Accepted 13 January 2010

Published online 12 February 2010 in Wiley InterScience (www.interscience.wiley.com).

E. K. S. was supported by National Institutes of Health Grants T32 DK07191-32 (to Daniel K. Podolsky in the Department of Gastroenterology at Massachusetts General Hospital), F32 DK079466-01, and K23 DK080145-01. The Framingham Heart Study is supported by core contract N01-HC25195. Additional research support was provided by an American Diabetes Association Career Development Award (to J. B. M.), the General Clinical Research Centers Program (Grant No. M01-RR-01066), and National Institute of Diabetes and Digestive and Kidney Diseases Grant K24 DK080140 (to J. B. M.).

Potential conflict of interest: D. V. S. has a research agreement with General Electric and is on the Speakers' Bureau of Bracco Diagnostics. J. B. M. currently has research grants from GlaxoSmithKline and sanofi-aventis, and has consulting agreements with Eli Lilly and Interleukin Genetics. Dr. Hirshhorn advises Correlagen Diagnostics, Inc.

Additional Supporting Information may be found in the online version of this article.

Abstract

Obesity is not uniformly associated with the development of metabolic sequelae. Specific patterns of body fat distribution, in particular fatty liver, may preferentially predispose at-risk individuals to disease. In this study, we characterize the metabolic correlates of fat in the liver in a large community-based sample with and without respect to visceral fat. Fatty liver was measured by way of multidetector computed tomography of the abdomen in 2,589 individuals from the community-based Framingham Heart Study. Logistic and linear regression were used to determine the associations of fatty liver with cardio-metabolic risk factors adjusted for covariates with and without adjustment for other fat depots (body mass index, waist circumference, and visceral adipose tissue). The prevalence of fatty liver was 17%. Compared with participants without fatty liver, individuals with fatty liver had a higher adjusted odds ratio (OR) of diabetes (OR 2.98, 95% confidence interval [CI] 2.12-4.21), metabolic syndrome (OR 5.22, 95% CI 4.15-6.57), hypertension (OR 2.73, 95% CI 2.16-3.44), impaired fasting glucose (OR 2.95, 95% CI 2.32-3.75), insulin resistance (OR 6.16, 95% CI 4.90-7.76); higher triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP); and lower high-density lipoprotein (HDL) and adiponectin levels ( P < 0.001 for all). After adjustment for other fat depots, fatty liver remained associated with diabetes, hypertension, impaired fasting glucose, metabolic syndrome, HDL, triglycerides, and adiponectin levels (all** **_P_** **< 0.001), whereas associations with SBP and DBP were attenuated (** **_P_** **> 0.05). Conclusion: Fatty liver is a prevalent condition and is characterized by dysglycemia and dyslipidemia independent of visceral adipose tissue and other obesity measures. This work begins to dissect the specific links between fat depots and metabolic disease. (Hepatology 2010;)