The impact of type 2 diabetes on tendon material properties and locomotor function in the db/db mouse

Obesity affects billions of individuals world-wide and brings with it greater susceptibility to secondary conditions, like that of type 2 diabetes mellitus (T2DM). One of the most effective therapeutic treatment strategies for obesity and T2DM is exercise, yet both populations present with severe exercise intolerance. Understanding the mechanisms driving this impaired locomotor/exercise function may help to better design therapeutic treatment strategies and exercise training regimes. Here, using a diabetic mouse model (db/db), we explore the functional decline of tendons and the subsequent impact on locomotor function. Firstly, we present measurements of ex vivo viscoelastic and tensile properties for the Achilles tendon in diabetic and wild-type mice. The results show that while the viscoelastic properties (tendon hysteresis and stress-relaxation) do not change, the diabetic tendons present with impaired uncrimping of the collagen fibres, resulting in an increased strain at physiological stresses. Next, we built mouse-specific hindlimb musculoskeletal models incorporating body mass and tendon material properties to predict the impact of changing physiology on locomotor function. Diabetic mouse models showed significant increases in muscle activation and metabolic output, alongside shifts to a less spring-like and more negative work-dominated brake-like function in the more tendinous muscles of the hindlimb. Together, our experimental and modelling data indicate that db/db mice generate larger degrees of muscle power to move the same distance, driven by the combined effects of increased body mass and tendon compliance. Alleviating either of these physiological issues may help recover patients' exercise tolerance and improve their overall quality of life.