Liver Fat Content in Type 2 Diabetes: Relationship With Hepatic Perfusion and Substrate Metabolism
- Luuk J. Rijzewijk1,
- Rutger W. van der Meer2,
- Mark Lubberink3,
- Hildo J. Lamb2,
- Johannes A. Romijn4,
- Albert de Roos2,
- Jos W. Twisk5,
- Robert J. Heine1,6,
- Adriaan A. Lammertsma3,
- Johannes W.A. Smit4 and
- Michaela Diamant1
- 1Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands;
- 2Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands;
- 3Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands;
- 4Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands;
- 5Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands;
- 6Eli Lilly & Company, Indianapolis, Indiana.
- Corresponding author: Luuk J. Rijzewijk, rijzewijk{at}vumc.nl.
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L.J.R. and R.W.v.d.M. contributed equally to this study.
Abstract
OBJECTIVE Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content.
RESEARCH DESIGN AND METHODS Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%.
RESULTS Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = −0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = −0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = −0.329, P = 0.004).
CONCLUSIONS In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received August 12, 2009.
- Accepted July 27, 2010.
- © 2010 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
