Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study.
OBJECTIVE
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.
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Ryan L
RL
McKimmie
Kurt R
KR
Daniel
J Jeffrey
JJ
Carr
Donald W
DW
Bowden
Barry I
BI
Freedman
Thomas C
TC
Register
Fang-Chi
FC
Hsu
Kurt K
KK
Lohman
Richard B
RB
Weinberg
Lynne E
LE
Wagenknecht
D050154:Adiposity; D000368:Aged; D050197:Atherosclerosis; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000000981:diagnostic imaging; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D002339:Carotid Arteries; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D005234:Fatty Liver / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors
D015415:Biomarkers