Insulin Resistance and Cognitive Decline May Be Common Soil for Frailty Syndrome

In the April, 2007, issue of the Archives, Barzilay et al¹ reported that 2 components of the metabolic syndrome, insulin resistance (IR) and inflammation, are associated with the risk of frailty in older persons with out diabetes mellitus, severe cognitive impairment, or other chronic illnesses. Using the homeostasis model of assessment (HOMA), they found that IR and C-reactive protein were consistently associated with an increased risk of developing frailty, even after adjusting for confounders. The authors propose that there is a causative relationship between IR and frailty. Specifically, they propose that the progressive age-associated decline of insulin sensitivity causes an imbalance toward catabolism, which is clinically expressed as an accelerated decline of muscle mass and strength. Such findings further substantiate previous findings from the “Invecchiare in Chianti” (InCHIANTI) study showing that IR-HOMA score was independently associated with poor muscle strength in older persons.² Barzilay et al¹ also hypothesized the existence of an inflammatory IR pathway that could contribute to muscle weakness and poor physical performance. An independent cross-sectional relationship between inflammatory markers and IR-HOMA score was previously suggested from analyses performed in the InCHIANTI database that underlined significant associations among IR and diverse inflammatory cytokines.³ Interestingly, Barzilay et al¹ did not consider cognitive decline as part of their outcome. Indeed, cognitive impairment is often observed in frail older persons, and several authors have proposed that cognitive impairment should be an essential component of the frailty definition.⁴