Towards a better understanding of diabetic neuropathies in hands: A comprehensive assessment of nerve function, structure and mechanical properties

Distal symmetrical polyneuropathy (DSPN) is the most common complication in diabetes but little is known about how diabetes affects the nerves that supply the hands or why some people with DSPN develop neuropathic pain. This thesis assessed the structure, function, and mechanical properties of peripheral nerves using non-invasive methods in healthy individuals (n=31), people with diabetes without DSPN (n=35), with DSPN in feet only (n=31), and with DSPN in hands and feet (n=28). Quantitative sensory tests showed that people with DSPN presented with severe loss of nerve function in their hands, even if DSPN symptoms were only present in the feet. Diffusion MRI analyses showed microstructural changes in the nerves supplying the hands in people with DSPN in hands, in people with DSPN in feet, and in people with diabetes without DSPN. Shear-wave elastography revealed increased nerve stiffness. Regarding neuropathic pain in DSPN, our systematic review and meta-analysis showed a reduction in painful detection thresholds in people with non-painful and painful DSPN. Corneal confocal microscopy showed progressive nerve fibre loss across groups. The proportion of people with abnormal corneal epithelial microneuromas and their prevalence increased in people with painful DSPN compared to all other groups, including non-painful DSPN. Our findings suggest a potential progression of structural, functional, and mechanical changes in peripheral nerves supplying the hands as diabetes and DSPN progress.