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  • Original Article
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Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

International Journal of Obesity volume 36, pages 709–717 (2012)Cite this article

Abstract

Objective:

To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects.

Design:

In this multi-center study, insulin sensitivity and β-cell function were assessed (n=102), using a euglycemic-hyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n=35).

Subjects:

A total of 102 subjects with IFG (n=48), IGT (n=12), IFG/IGT (n=26) and NGT (n=16).

Results:

IFG, IGT and IFG/IGT subjects had lower insulin sensitivity with no differences between groups, and lower impaired β-cell function compared with NGT controls. The early postprandial increase in triacylglycerol (TAG) concentration was higher (iAUC0−2 h IFG: 238.4±26.5, IGT: 234.0±41.0 and NGT: 82.6±13.8 μmol l−1 min−1, both P<0.05) and early TAG extraction was increased (AUC0−2 h IFG: 56.8±9.0, IGT: 52.2±12.0 and NGT: 3.8±15.4 nmol·100 ml−1 min−1, P<0.05 and P=0.057, respectively) in both IFG and IGT subjects.

Conclusion:

IFG, IGT and IFG/IGT subjects have lower insulin sensitivity and impaired β-cell function compared with age- and BMI-matched NGT controls. The increased postprandial TAG response and higher muscle TAG extraction in both IFG and IGT compared with NGT may lead to ectopic fat accumulation in the skeletal muscle, thereby contributing to insulin resistance.

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Acknowledgements

The authors would like to thank Anneke Jans and Ellen Konings for their excellent practical support, and Jos Stegen and Wendy Sluijsmans for technical assistance. An Investigator-Initiated Study Grant from Novartis Pharma supported this study. Clinical Trial Registration Number: ISRCTN42786336

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Author notes

  1. C C M Moors and N J van der Zijl: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands

    C C M Moors, E E Blaak & G H Goossens

  2. Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands

    N J van der Zijl & M Diamant

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  1. C C M Moors
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  2. N J van der Zijl
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  3. M Diamant
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Correspondence to C C M Moors.

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Moors, C., van der Zijl, N., Diamant, M. et al. Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism. Int J Obes 36, 709–717 (2012). https://doi.org/10.1038/ijo.2011.123

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