: The objective of this article is to review the mechanisms which the body uses to regulate its function. The author considers, in particular, the nature and structure of the physiological systems with a specific focus upon the systemic regulation of blood glucose and highlights an innovative technology, based upon the top-down cognitive approach, which incorporates a unique mathematical model of the physiological systems and autonomic nervous system. Most systems biology is a development of the prevailing reductionist biomedical paradigm. It adopts a bottom-up approach seeking systemic justification for biochemical and biophysical research findings. By contrast the 'top-down' approach considers the neural regulation of the physiological systems and the neurological, cognitive and biochemical consequences of systemic dysfunction i.e. the consequences of sensory input upon the neural regulation of the body's systems, organs, and its cellular and molecular biochemistry. In conclusion, the evidence suggests that the onset and progression of Diabetes Mellitus cannot be accurately assessed by individual biomedical indices but instead that the regulation of blood glucose is one of a number of inter-related physiological systems which act in a coordinated manner in order to maintain the body's physiological stability.