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DOI: 10.2337/dc06-0455
© 2006 by the American Diabetes Association
Pathophysiology/Complications |
Influence of Hepatic Steatosis (Fatty Liver) on Severity and Composition of Dyslipidemia in Type 2 Diabetes
1 Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
2 Mike Rosenbloom Laboratory for Cardiovascular Research, Royal Victoria Hospital, Montreal, Quebec, Canada
Address correspondence and reprint requests to Frederico G.S. Toledo, MD, 807N Montefiore Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213. E-mail: toledofs{at}upmc.edu
OBJECTIVE—The objective of this study was to examine the associations between the severity of hepatic steatosis and dyslipidemia in type 2 diabetes, including circulating apolipoprotein B100 (apoB) concentrations and lipoprotein particle size and numbers.
RESEARCH DESIGN AND METHODS—Computed tomography imaging was used to assess hepatic fat content and adipose tissue distribution in 67 men and women with type 2 diabetes, withdrawn from antidiabetic medications preceding the study. Fasting serum lipoprotein number and size was determined by nuclear magnetic resonance. Insulin sensitivity was measured with a glucose clamp and a [6,6-2H2]glucose isotope infusion.
RESULTS—Two-thirds of the cohort had fatty liver. Hepatic steatosis correlated with serum triglycerides (r = 0.40, P < 0.01) and lower HDL cholesterol (r = –0.31, P < 0.05). ApoB and LDL cholesterol did not, being virtually identical in those with or without steatosis. The association between serum triglycerides and hepatic steatosis was largely accounted for by greater triglyceride enrichment in VLDL particles, which were larger. Severe steatosis was also associated with 70% higher small, dense LDL concentrations. Visceral obesity did not fully explain these associations, and hepatic steatosis was better correlated with triglycerides than with hyperglycemia or hepatic insulin resistance (P > 0.05).
CONCLUSIONS—The presence of hepatic steatosis in type 2 diabetes does not appear to affect apoB levels, but potentially increases atherogenesis by increasing triglycerides, reducing HDL levels, and increasing small, dense LDL.
Abbreviations: apoB, apolipoprotein B100 • EGP, endogenous glucose production • FFA, free fatty acid • IDL, intermediate-density lipoprotein • L/S ratio, ratio of liver to spleen • NMR, nuclear magnetic resonance • VAT, visceral adipose tissue
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