Characterisation of flowmotion in healthy controls and type 2 diabetes

Flowmotion, the rhythmic oscillation of blood flow across a tissue, optimises nutrient delivery at rest and during states of increased metabolic demand. Five known factors influence flowmotion patterns across a tissue, each distinguishable by their rate of input; cardiac, respiratory, myogenic, neurogenic and endothelial components. In disease states such as type 2 diabetes (T2D), flowmotion is thought to be altered and may contribute to dysregulated metabolism. The aim of this thesis was to characterise flowmotion in healthy controls and T2D participants. Flowmotion was investigated in healthy controls and T2D participants at rest, and following endogenous insulin release in response to a 50g oral glucose challenge (OGC). The effect of a resistance training (RT) intervention in T2D participants was also assessed. Total blood flow to the forearm was measured using 2D-ultrasound and skeletal muscle perfusion was measured with contrast enhanced ultrasound (CEU). Microvascular blood flow in the skin and subcutaneous tissue (skin+SC) of the forearm was examined using a combined Laser Doppler Flowmetry (LDF) and tissue oxygenation probe. Spectral analysis (wavelet transformation) was performed on the data to characterise the individual contributions of the five factors known to influence flowmotion. Type 2 diabetics exhibited differences in total blood flow, skin+SC LDF flux and skin+SC flowmotion compared to healthy controls at rest. Flowmotion was altered in response to the OGC in healthy controls, without changes in total flow and skin+SC LDF flux. In contrast, flowmotion and skin+SC LDF flux were unaltered in response to OGC in T2D, while total blood flow to the forearm increased. In the T2D group, a 6-week RT intervention partially restored skin+SC flowmotion. In response to OGC skeletal muscle microvascular perfusion was reduced in healthy controls, but not in T2D participants. In contrast, skin+SC microvascular perfusion did not change in response to OGC in either group, indicating skin+SC flowmotion may not represent flowmotion in skeletal muscle. The CEU technique, used to determine skeletal muscle microvascular perfusion, was adapted to investigate flowmotion within skeletal muscle. In anaesthetised rats, skeletal muscle flowmotion patterns were measured with both the LDF and the newly adapted CEU techniques. An ˜í¬±-adrenoceptor antagonist, which inhibits the neurogenic component of flowmotion, was used to compare the two techniques. Both the LDF and CEU methods detected the inhibition. In addition, the CEU method enable identification of different flowmotion patterns within specific fibre types. In conclusion, these studies demonstrate dysfunction in blood flow and flowmotion in T2D. They also highlight a difference in skin+SC and skeletal muscle microvascular blood flow in response to OGC. The newly adapted CEU technique will allow more informative assessment of flowmotion in skeletal muscle, facilitating future research into its role in regulation of muscle metabolism.