Background. Abdominal adiposity and serum leptin increase with age as does risk of metabolic syndrome. This study investigates the prospective association between leptin and metabolic syndrome risk in relation to adiposity and cytokines. Methods. The Health, Aging, and Body Composition study is a prospective cohort of older adults aged 70 to 79 years. Baseline measurements included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous fat. Multivariate logistic regression was used to determine the association between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after 6 years of follow-up among 1,120 men and women. Results. Leptin predicted metabolic syndrome in men ( for trend = 0.0002) and women ( for trend = 0.0001). In women, risk of metabolic syndrome increased with higher levels of leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile 3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential confounders. Leptin remained independently associated with metabolic syndrome risk after additional adjustment for adiposity, cytokines, and CRP. Among men, this association was no longer significant after controlling for adiposity. Conclusion. Among older women, elevated concentrations of leptin may increase the risk of metabolic syndrome independent of adiposity and cytokines. 1. Introduction Leptin is an adipocyte-derived hormone that influences appetite [1] and reflects amount of energy stored in adipose tissues [2, 3]. The association between plasma leptin and fat mass is disrupted with aging [4]. Aging is accompanied by an increase in serum leptin levels [2], proinflammatory cytokines, such as TNF- [5, 6], and prevalence of metabolic syndrome [7]. Leptin also plays a critical role in the inflammatory response [8] and has been associated with insulin resistance [9] and metabolic syndrome [7]. Leptin directly inhibits insulin secretion from pancreatic -cells [10] and elevated serum leptin levels are associated with fasting insulin, insulin resistance (HOMA-IR), and total cholesterol [11–15], the core metabolic disturbances of the metabolic syndrome. Although the proinflammatory cytokines are associated with serum leptin and have been implicated in the development of metabolic syndrome, the prospective association of serum leptin with metabolic syndrome has not been explored independently of proinflammatory cytokines and body fat depots among older adults. The primary objective of this study is to examine
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