Jensen Christine B, Storgaard Heidi, Madsbad Sten, Richter Erik A, Vaag Allan A
Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark.
J Clin Endocrinol Metab. 2007 Apr;92(4):1530-4. doi: 10.1210/jc.2006-2360. Epub 2007 Feb 6.
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. 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.
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.
Vastus lateralis muscle was obtained by percutaneous biopsy from 20 healthy 19-yr-old men with birth weights at 10th percentile or lower for gestational age (LBW) and 20 normal birth weight controls, 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; normal birth weight, n=12).
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.
Alterations in fiber composition and size may contribute to development of type 2 diabetes in individuals with LBW.
低出生体重(LBW)是不良胎儿环境的一个替代指标,与肌肉胰岛素抵抗、胰岛素刺激的糖酵解受损以及2型糖尿病的未来风险相关。骨骼肌质量、纤维组成和毛细血管密度是肌肉功能和代谢的重要决定因素,其改变与胰岛素抵抗的发病机制有关。
本研究旨在调查不良胎儿环境(低出生体重)是否会导致骨骼肌形态的永久性改变,这可能有助于解释与低出生体重相关的代谢紊乱表型。
通过经皮活检从20名健康的19岁男性获取股外侧肌,这些男性的出生体重处于胎龄第10百分位数或更低(低出生体重),并选取20名正常出生体重的对照者,根据体脂、身体素质和全身葡萄糖处置情况进行匹配。采用肌原纤维ATP酶染色将肌纤维分为I型、IIa型和IIx型(原IIb型),并进行双重免疫染色以标记毛细血管(低出生体重组,n = 8;正常出生体重组,n = 12)。
低出生体重与IIx型纤维比例增加(+66%;P = 0.03)相关,代价是IIa型纤维比例降低(-22%;P = 0.003)。I型纤维比例无显著变化(+16%;P = 0.11)。此外,IIa型纤维的平均面积增加(+29%;P = 0.01),I型纤维的平均面积也有增加趋势(+17%;P = 0.08)。两组之间的毛细血管密度无显著差异。
纤维组成和大小的改变可能有助于低出生体重个体发生2型糖尿病。