Liver fat content in type 2 diabetes: relationship with hepatic perfusion and substrate metabolism

  1. Michaela Diamant, MD, PhD1
  1. 1Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
  4. 4Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  6. 6Eli Lilly & Company, Indianapolis, IN,USA

Abstract

Objective. Hepatic steatosis is common in type 2 diabetes mellitus (T2DM). 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 present 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 T2DM and 18 age matched healthy normoglycemic men were studied using positron emission tomography (PET) 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 (MR) spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (T2DM-low) or above (T2DM-high) the median of 8.6%.

Results. T2DM-high patients had the highest BMI, HbA1c and lowest whole-body insulin sensitivity (ANOVA, all P<0.001). Compared to controls and T2DM-low patients, T2DM-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 T2DM 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, T2DM 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.

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    1. Diabetes
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