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

Abstract

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. 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. 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. 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.