Abstract
Obesity has been associated with higher risk of frailty in older adults, but the pathophysiological mechanisms are unclear. No previous study has examined the association between leptin, an adipokine, and the risk of frailty in older adults, and whether this association could be explained by insulin resistance or chronic inflammation. Data were taken from 1,573 individuals without diabetes mellitus, aged ≥60 years, from the Seniors-ENRICA cohort. In 2008-2010, leptin, the homeostasis model assessment of insulin resistance (HOMA-IR) and C-reactive protein (CRP) were measured. Study participants were followed-up through 2012 to assess incident frailty, defined as at least two of the following Fried criteria: exhaustion, weakness, low physical activity, and slow walking speed. Analyses were performed with logistic regression and adjusted for the main confounders. Over a median follow-up of 3.5 years, 280 cases of incident frailty were identified. Compared to individuals in the lowest tertile of serum leptin, those in the highest tertile showed an increased risk of frailty (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.47-3.06; p-trend <0.001). Further adjustment for the percentage of body fat led to an OR of 1.69 (95% CI: 1.11-2.61; p-trend=0.01). After additional adjustment for HOMA-IR and CRP, the OR for frailty was 1.59 (95% CI: 1.01-2.52; p-trend=0.04). Results did not vary according to sex, abdominal obesity or the percentage of body fat. Being in the highest versus lowest tertile of leptin was associated with increased risk of exhaustion (OR: 2.16; 95% CI: 1.32-3.55; p-trend=0.001) and muscle weakness (OR: 1.77; 95% CI: 1.25-2.51; p-trend=0.001), in the analyses adjusted for potential confounders and body fat. Higher leptin concentration was associated with greater risk of frailty in older adults. This association was only modestly explained by insulin resistance and chronic inflammation, as measured by CRP.