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

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 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 males (T2DM vs. control, n = 24/group) were sampled < 24h post-mortem. Analysis included myosin-heavy-chain fibre typing, Sudan Black B IMCL quantification, and 3D capillary morphometry (length, tortuosity, anisotropy, branching density). Groups were age-matched (T2DM 70.8 ± 7.4 vs 69.7 ± 11.8 years; p = 0.684), but BMI was higher in T2DM (31.9 ± 4.7 vs 24.8 ± 2.7 kg/m²; 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 associated negatively 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, with adiposity-linked IMCL accumulation and reduced DIA capillary supply despite largely preserved global architecture, suggesting selective metabolic and microvascular vulnerability.