[Insulin resistance as a mechanism of adaptation during human evolution]

The recent application of concepts of evolution to human disease is proving useful to understand certain pathophysiological mechanisms of different entities that span genomic alterations of immunity, respiratory and hormone function, and the circulatory and neural systems. However, effort has concentrated on explaining the keys to adaptation that define human metabolism and, since the early 1960s, several theories have been developed. This article reviews some of the hypotheses postulated in recent years on the potential benefit of insulin resistance and discusses the most recent knowledge. The concept of the thrifty gene seems to have been definitively refuted by current knowledge. The current paradigm describes an interaction between the metabolic and the immune systems resulting from their coevolution, promoted by evolutionary pressures triggered by fasting, infection and intake of different foods. The activation and regulation of these ancient mechanisms in integrated and interdependent areas defines insulin resistance as a survival strategy that is critical during fasting and in the fight against infection. The relationship with some components of the diet and, particularly, with the symbiotic intestinal microflora points to new paradigms in understanding the pathophysiology of obesity, metabolic syndrome and type 2 diabetes mellitus.