Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395

I read with great interest the recent article by Prior et al. (1), in which muscle biopsies and the hyperinsulinemic-euglycemic clamp were combined to interrogate the role of the exercise-induced increase in skeletal muscle capillarization on insulin sensitivity. Specifically, the effects of 6 months of endurance training and 2 weeks of detraining on intramuscular signaling, capillarization, and whole-body insulin sensitivity were determined in older sedentary individuals. This study represents a further step toward understanding the mechanisms underlying the beneficial effects of exercise training on insulin sensitivity and glucose tolerance. Here, I would like to address two issues that may buttress, or perhaps moderate, the main conclusion of the accomplished work of Prior et al. (1).

The first issue refers to the independent nature of the association between the changes (detraining − baseline) in capillary density (CD) and insulin sensitivity, which was merely adjusted by sex and changes in percentage body fat. In this respect, the authors could have additionally accounted for HDL cholesterol, which has been associated with insulin-mediated microvascular vasomotion facilitating nutrient and hormone delivery (2) and insulin sensitivity (3). Interestingly, HDL cholesterol levels were increased with training and remained elevated after detraining, matching the pattern observed for insulin sensitivity (1).

The second issue concerns the exclusive use of CD (capillaries per mm² of muscle area) as the measure of skeletal muscle capillarization (1). In this regard, although muscle fiber areas were unaltered with training and detraining (1), changes in CD may be also influenced by those of the muscle interstitial area (4), which were not documented (1). Alternatively, skeletal muscle capillarization may be characterized by the area-independent capillary-to-fiber ratio (C:F), as previously reported by the authors (5–7). C:F is likewise less prone than CD to be affected by tissue handling during the biopsy procedure (8). Of note, large cross-sectional studies indicate that, unlike CD, C:F is not associated with insulin sensitivity in aged individuals (9). Taken together, the effect of exercise-induced skeletal muscle capillarization on insulin sensitivity evidenced by Prior et al. (1) could be further elucidated with the report of muscle interstitial area and/or C:F measures.