Insulin resistance is closely associated with both aging and overweight; yet in old age, weight loss is common, although insulin resistance increases. To study this paradox, the authors evaluated the role of insulin resistance in weight change among older adults from the Rancho Bernardo Study cohort. Participants were 725 nondiabetic men and women who were aged 50-89 years when weight and insulin were measured at baseline (1984)(1985)(1986)(1987). The participants were evaluated again in

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... 96, at which time weight was remeasured. Fasting insulin and homeostasis model assessment (HOMA) measurements were evaluated in separate but parallel statistical models as surrogates for insulin resistance. Insulin resistance, when defined as the top quartile of fasting insulin level or HOMA value, was significantly associated with weight loss before and after adjustment for baseline weight and age (fasting insulin: β = -1.30 kg, p = 0.01; HOMA: β = -1.18 kg, p = 0.01). Results were the same for men versus women, for the overweight (body mass index (weight (kg)/height (m) 2 ) ≤26.6) versus the normal weight (body mass index >26.6), and for younger persons (age <70 years) versus older persons (age ≥70 years). Insulin-resistant individuals had a threefold increased likelihood of losing 10 or more kg compared with those without insulin resistance. The authors conclude that hyperinsulinemia, independently of age and baseline weight, may have a catabolic effect in the elderly. Am J Epidemiol 2001;153:1199-205.