Research Article Details

Article ID: A52957
PMID: 18853970
Source: Am J Gastroenterol
Title: Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study.
Abstract: 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.
DOI: 10.1111/j.1572-0241.2008.02188.x

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I07 1936 Arteriosclerosis Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D095 Cysteamine bitartrate Chemical drug DB00847 -- -- Under clinical trials Details
D094 Cysteamine Chemical drug DB00847 GSS stimulant Renal drug Under clinical trials Details
D055 Calcium Chemical drug DB01373 CAST; COMP; CP; BMP4; MGP -- Under clinical trials Details