Obesity is one of the most important factors responsible for the marked increase in both the incidence and prevalence of type 2 diabetes mellitus (T2DM) in recent decades. Addressing the lifestyle factors associated with the progression to T2DM would present a potential rational early prevention strategy. The current evidence suggests that excessive energy intake is mediated via dietary fat. Biochemical signals released in response to the ingestion of food require supportive signalling from the presence of food in the stomach. The degree of supportive volume signalling emanating from the stomach influences both the satiation and satiety phases. The Lipids and Volume in Satiation and Satiety (LIVES) Hypothesis proposes that the biological feedback from fat intake appears to be influenced by the other macronutrients with which it is consumed. By identifying the various possible macronutrient combinations with fat, it is possible to construct a matrix of food composition/volume scenarios, which may help elucidate dysfunction in the human food energy regulation system within the context of the modern food environment.