Two models of insulin resistance development and the strategy to combat age-related diseases: literature review

Abstract

BACKGROUND: Insulin resistance (IR) is the root cause of most age-related diseases (ARD), the major challenge for today’s health systems. Therefore, adequate understanding of the mechanisms underlying IR is essential to build effective ARD prevention.OBJECTIVE: Analyze the existing models of IR causation and progression in order to justify the most effective ARD prevention strategy.METHODS: Search and analysis of publications on IR and hyperinsulinemia (HI) from databases elibrary.ru, PubMed, and Google Scholar.RESULTS: Two models of IR development are analyzed along with the relationship between IR, HI, and obesity. The prevailing model considers obesity (imbalance of caloric intake and energy expenditure) as the main factor in the development of IR; HI is seen as a consequence of IR, mostly insignificant for the outcomes of IR. The model contradicts many experimental and clinical findings. The strategy to combat ARDs that follows from the model (hypocaloric diet and pharmacotherapy of IR) has proven mostly ineffective.The alternative model (IR as a consequence of HI, and obesity as one of IR manifestations) is more consistent with the pool of experimental and clinical data. It more precisely predicts ARD development and allows more adequate correction of adverse lifestyle factors. It corresponds to a different strategy for combating ARD: emphasis on low-carb diet and longer fasting window combined with consideration of other factors of IR.CONCLUSION: If the prevailing model of IR development is revised, this should open up opportunities for more effective early prevention of a wide range of chronic diseases in which the role of IR is significant.