Fat Mass Accounts for Insulin Resistance Impact on Functional Decline and Mortality in Nondiabetic Older Adults

Abstract

ObjectiveTo assess the potential role of body composition in the association of insulin resistance (IR) with functional decline and mortality in nondiabetic older persons. DesignLongitudinal population-based cohort of community-dwelling people from Toledo, Spain, aged 65 years or older. Setting and ParticipantsA total of 1114 nondiabetic persons from the Toledo Study of Healthy Aging cohort (mean age: 74.5, 56.10% female) with complete data at baseline were included. Only 914 participants had fully assessment of functional evaluation during the follow-up period. MethodsIR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 2.99 years’ median follow-up period. A total of 319 participants experienced functional decline (2.5-point reduction in the FTS-5 score). A total of 143 deaths were recorded (6.31 years median follow-up) from the Spanish National Death Index. Body compositions were determined using dual-energy x-ray absorptiometry. Multivariate regression models analyzed the effect of HOMA-IR on outcomes, with age, sex, Charlson index, and number of medications included in the basic adjustment model. ResultsA 1-logaritmic unit increment in HOMA-IR increased the risk of functional decline after basic adjustment [odds ratio (95% confidence interval): 1.41 (1.09–1.83), P = .009]. This significant association was lost when further adjusted for total fat mass [1.14 (0.86–1.50)] and trunk fat mass [1.03 (0.77–1.37)], which accounted for 62.92% and 91.49% of the association. HOMA-IR was inversely associated with mortality risk [hazard ratio 0.66 (0.49–0.87), P = .0037], an association lost after adjustment for total fat mass [0.74 (0.55–1.01)] and trunk fat mass [0.80 (0.58–1.09)], accounting for 29.05% and 45.78% of the association. Adjustment by lean mass did not modify any of the associations. Conclusions and ImplicationsBody fat mass, especially in the trunk region, mediates the association of IR with functional decline and to a lesser extent with reduced risk of mortality in nondiabetic older subjects.