Diabesity, that is to say, obesity-dependent diabetes, has emerged as a major public health problem. Though diabesity is basically explained by insulin resistance and pancreatic beta cell dysfunction, new paradigms have evolved to explain these alterations in the context of the modern epidemics of obesity and diabetes. Among these, the association of inflammation with obesity is an important component of the common soil from which diabetes and cardiovascular diseases (CVD) derive. This Review presents our epidemiological findings, based primarily on the ARIC Study, in the context of the other epidemiological studies supporting the inflammatory nature of diabetes, CVD and the metabolic syndrome. We also review the characteristics of the innate immune system, including the molecular interface of innate immunity with metabolism, components of which are responsible for the presence of a state of mild, chronic and systemic inflammation related to diabesity. Finally, we present obesity as an inflammatory condition, obesitis, and propose a conceptual framework that integrates the epidemiological findings with new provocative basic science results.