Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study

Am J Gastroenterol. 2008 Dec;103(12):3029-35. doi: 10.1111/j.1572-0241.2008.02188.x. Epub 2008 Oct 3.


Objectives: To explore mechanisms whereby hepatic steatosis may be associated with cardiovascular risk, we investigated cross-sectional relationships between hepatic steatosis, regional fat accumulation, inflammatory biomarkers, and subclinical measures of atherosclerosis in the Diabetes Heart Study.

Methods: The Diabetes Heart Study is a family study of sibling pairs concordant for type 2 diabetes. A subset of 623 randomly selected participants was evaluated for hepatic steatosis, defined as a liver:spleen attenuation ratio of <1.0 by computed tomography. We quantified visceral fat, subcutaneous fat, coronary, aortic, and carotid artery calcium by computed tomography; and carotid atherosclerosis by ultrasound. Associations between the liver:spleen attenuation ratio and these factors were expressed as Spearman correlations.

Results: After adjustment for age, race, gender, body mass index, and diabetes status, the liver:spleen attenuation ratio correlated with visceral fat (r =-0.22, P < 0.0001) and subcutaneous fat (r =-0.13, P= 0.031). Hepatic steatosis was associated with lower high-density lipoprotein (r = 0.21, P < 0.0001), higher triglycerides (r =-0.25, P < 0.0001), higher C-reactive protein (r =-0.095, P= 0.004), and lower serum adiponectin (r = 0.34, P < 0.0001). There were no significant associations between the liver:spleen attenuation ratio and coronary, aortic, or carotid calcium, or carotid intimal thickness.

Conclusions: This suggests that hepatic steatosis is less likely a direct mediator of cardiovascular disease and may best be described as an epiphenomenon. The strong correlations between pro-atherogenic biomarkers, visceral fat, and elements of the metabolic syndrome suggest that hepatic steatosis reflects more than general adiposity, but represents a systemic, inflammatory, pro-atherogenic adipose state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Aged
  • Atherosclerosis
  • Biomarkers / blood
  • Calcinosis / diagnostic imaging
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Carotid Arteries
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Fatty Liver / blood
  • Fatty Liver / complications*
  • Female
  • Humans
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications
  • Middle Aged
  • Radiography
  • Risk Factors


  • Biomarkers