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<p>In type 2 diabetes mellitus (T2DM), skeletal muscle is a major site of metabolic and microvascular dysfunction, yet most human data derive from large locomotor muscles, whereas postural and respiratory muscles remain less well characterised. We examined whether T2DM alters fibre morphology, intramyocellular lipid (IMCL) content, and three-dimensional (3D) capillary architecture across functionally distinct muscles. Postural (splenius capitis [SC]), respiratory (diaphragm [DIA]; external intercostal [EXT]), and locomotor (vastus lateralis [VL]) muscles from adult male individuals&#xa0;(T2DM versus control, <i>n</i> = 24/group) were sampled &lt; 24&#xa0;h post-mortem. Analysis included myosin heavy chain fibre typing, Sudan Black B intramyocellular lipid (IMCL) quantification, and 3D capillary morphometry (length, tortuosity, anisotropy, branching density). Groups were age-matched (T2DM 70.8 ± 7.4 versus 69.7 ± 11.8&#xa0;years; <i>p</i>&#xa0;= 0.684), but body mass index (BMI) was higher in T2DM (31.9 ± 4.7 versus 24.8 ± 2.7&#xa0;kg&#xa0;m<sup>−2</sup>; <i>p</i> &lt; 0.0001). Fibre-type profiles were similar, except for elevated 2a/2x hybrids in T2DM VL (<i>p</i> = 0.014). Mean fibre diameters were preserved, though type 1 fibres were larger in T2DM SC (<i>p</i> = 0.0238). IMCL was higher in T2DM SC and EXT (<i>p</i> &lt; 0.05), with non-significant differences in VL and DIA. Type 1 and 2a fibres had higher IMCL than glycolytic fibres, with no group-by-fibre-type interaction. BMI strongly predicted VL IMCL (<i>p</i> &lt; 0.0001), while age was negatively associated with IMCL in respiratory muscles (<i>p</i> ≤ 0.05). Capillary length per fibre volume was selectively reduced in DIA (<i>p</i> = 0.0115); other indices were preserved, except for higher anisotropy in EXT (<i>p</i> = 0.0495). Overall, these functionally diverse muscles showed subtle muscle-specific remodelling in T2DM, with adiposity-linked IMCL accumulation and reduced DIA capillary supply, although findings should be interpreted in the context of the post-mortem study.</p>

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Fibre morphology, intramyocellular lipid content and 3D capillary architecture in human postural, respiratory and locomotor muscles in type 2 diabetes mellitus

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  • 发表日期：

    2026年4月6日

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  • Nataša Pollak,
  • Jiří Janáček,
  • František Saudek,
  • Erika Cvetko,
  • Barbora Radochová,
  • Armin Alibegović,
  • Chiedozie Kenneth Ugwoke,
  • Davide Alessandro Basello,
  • Žiga Šink,
  • Luka Pušnik,
  • Rok Tit Tomazin,
  • Nejc Umek

摘要

In type 2 diabetes mellitus (T2DM), skeletal muscle is a major site of metabolic and microvascular dysfunction, yet most human data derive from large locomotor muscles, whereas postural and respiratory muscles remain less well characterised. We examined whether T2DM alters fibre morphology, intramyocellular lipid (IMCL) content, and three-dimensional (3D) capillary architecture across functionally distinct muscles. Postural (splenius capitis [SC]), respiratory (diaphragm [DIA]; external intercostal [EXT]), and locomotor (vastus lateralis [VL]) muscles from adult male individuals (T2DM versus control, n = 24/group) were sampled < 24 h post-mortem. Analysis included myosin heavy chain fibre typing, Sudan Black B intramyocellular lipid (IMCL) quantification, and 3D capillary morphometry (length, tortuosity, anisotropy, branching density). Groups were age-matched (T2DM 70.8 ± 7.4 versus 69.7 ± 11.8 years; p = 0.684), but body mass index (BMI) was higher in T2DM (31.9 ± 4.7 versus 24.8 ± 2.7 kg m−2; p < 0.0001). Fibre-type profiles were similar, except for elevated 2a/2x hybrids in T2DM VL (p = 0.014). Mean fibre diameters were preserved, though type 1 fibres were larger in T2DM SC (p = 0.0238). IMCL was higher in T2DM SC and EXT (p < 0.05), with non-significant differences in VL and DIA. Type 1 and 2a fibres had higher IMCL than glycolytic fibres, with no group-by-fibre-type interaction. BMI strongly predicted VL IMCL (p < 0.0001), while age was negatively associated with IMCL in respiratory muscles (p ≤ 0.05). Capillary length per fibre volume was selectively reduced in DIA (p = 0.0115); other indices were preserved, except for higher anisotropy in EXT (p = 0.0495). Overall, these functionally diverse muscles showed subtle muscle-specific remodelling in T2DM, with adiposity-linked IMCL accumulation and reduced DIA capillary supply, although findings should be interpreted in the context of the post-mortem study.