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Reproducibility of glucose, fatty acid and VLDL kinetics and multi-organ insulin sensitivity in obese subjects with non-alcoholic fatty liver disease

International Journal of Obesity volume 35, pages 1233–1240 (2011)Cite this article

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Abstract

Objective:

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities in basal glucose and free fatty acid (FFA) metabolism, multi-organ insulin resistance and alterations in lipoprotein kinetics. These metabolic outcomes can be evaluated in vivo by using stable isotopically labeled tracer methods. An understanding of the reproducibility of these measures is necessary to ensure adequate statistical power in studies designed to evaluate metabolic function in subjects with NAFLD.

Methods:

We determined the degree of intra-individual variability of skeletal muscle, adipose tissue, and hepatic insulin sensitivity and basal plasma glucose, FFA, and very-low-density lipoprotein triglyceride and apolipoprotein B-100 (apoB-100) kinetics in eight obese subjects with NAFLD (age: 44±3 years; body mass index: 38.2±1.7 kg m−2; intrahepatic triglyceride content: 24.5±3.9%), by using the hyperinsulinemic-euglycemic clamp technique and stable isotope-labeled tracer methods and mathematical modeling on two separate occasions ∼2 months apart.

Results:

The intra-individual variability (coefficient of variation) ranged from 6% for basal glucose production to 21% for insulin-stimulated glucose disposal (percentage increase from basal). We estimated that a 25% difference in any outcome measure can be detected with a sample size of ⩽8 subjects for paired studies and ⩽15 subjects per group for unpaired studies, assuming an α value of 0.05 and a β value of 0.20 (that is, 80% power).

Conclusion:

These results demonstrate that only a small number of subjects are needed to detect clinically relevant effects in insulin sensitivity and hepatic lipoprotein metabolism in obese subjects with NAFLD, and will be useful to determine appropriate sample size for future metabolic studies.

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Acknowledgements

This study was supported by National Institutes of Health grants DK 37948, DK 56341 (Nutrition Obesity Research Center), RR024992 (Clinical and Translational Science Award) and RR-00954 (Biomedical Mass Spectrometry Resource). The authors thank Freida Custodio and Jennifer Shew for technical assistance, the staff of the Clinical Research Unit for their help in performing the studies and the study subjects for their participation.

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  1. F Magkos

    Present address: 4Current address: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,

Authors and Affiliations

  1. Center for Human Nutrition, Washington University School of Medicine, St Louis, MO, USA

    F Magkos, E Fabbrini, K Korenblat, A L Okunade, B W Patterson & S Klein

  2. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece

    F Magkos

  3. Department of Medical Sciences, Center for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy

    E Fabbrini

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Correspondence to S Klein.

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Magkos, F., Fabbrini, E., Korenblat, K. et al. Reproducibility of glucose, fatty acid and VLDL kinetics and multi-organ insulin sensitivity in obese subjects with non-alcoholic fatty liver disease. Int J Obes 35, 1233–1240 (2011). https://doi.org/10.1038/ijo.2010.265

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