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This version published online on February 6, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2360
A more recent version of this article appeared on April 1, 2007
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Submitted on October 27, 2006
Accepted on January 25, 2007

Altered Skeletal Muscle Fiber Composition and Size Precede Whole-body Insulin Resistance in Young Men with Low Birth Weight

Christine B. Jensen*, Heidi Storgaard, Sten Madsbad, Erik A. Richter, and Allan A. Vaag

Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, DK-Denmark; Dept. of Human Physiology, Copenhagen Muscle Research Centre, Inst. of Exercise and Sport Sciences, Universitetsparken 13, University of Copenhagen, DK-2100 Copenhagen, Denmark; Dept of Endocrinology, Hvidovre University Hospital, Kettegaards Allé 30, 2630 Hvidovre, Denmark

* To whom correspondence should be addressed. E-mail: CBJJ{at}steno.dk.

Context: Low birth weight (LBW), a surrogate marker of an adverse fetal milieu, is linked to muscle insulin resistance, impaired insulin-stimulated glycolysis and future risk of type 2 diabetes (T2D). Skeletal muscle mass, fiber composition and capillary density are important determinants of muscle function and metabolism, and alterations have been implicated in the pathogenesis of insulin resistance.

Objective: The aim of this study was to investigate whether an adverse fetal environment (LBW) induces permanent changes in skeletal muscle morphology, which may contribute to the dysmetabolic phenotype associated with LBW.

Design and Subjects: Vastus lateralis muscle was obtained by percutaneous biopsy from 20 healthy 19-yr old men with birth weights ≤ 10th percentile for gestational age (LBW) and 20 normal birth weight controls (NBW), matched for body fat, physical fitness and whole-body glucose disposal. Myofibrillar ATPase staining was used to classify muscle fibers as Type I, IIa and IIx (formerly Type IIb), and double immunostaining was performed to stain capillaries (LBW: N=8, NBW: N=12).

Results: LBW was associated with increased proportion of Type IIx fibers (+66%. P=0.03), at the expense of decreased Type IIa fibers (-22%, P=0.003). No significant change was observed in proportion of Type I fibers (+16%, P=0.11). In addition, mean area of Type IIa fibers was increased (+29%, P=0.01), and tended to be increased for Type I fibers as well (+17%, P=0.08). Capillary density was not significantly different between groups.

Conclusion: Alterations in fiber composition and size may contribute to development of T2D in individuals with LBW.


Key words: Muscle • fiber type • low birth weight • fetal programming • insulin resistance • Type 2 diabetes




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