BACKGROUND: Con¯icting research ®ndings have created uncertainty as to the ideal body weight. OBJECTIVE: To test whether average-adulthood BMI (body mass index, weight in kilograms per height in meters squared) is a more reliable predictor of mortality risk than the one-time baseline BMI measurement which has been used in previous studies. DESIGN: Prospective cohort study with a 20 y follow-up period, the First National Health and Examination Survey (NHANES 1) Epidemiologic Follow-up Study (NHEFS). SUBJECTS: A random probability sample of 14 407 adults aged 25±74 y in the 1971±1975 NHANES 1. MEASUREMENTS: Body-weight data were derived from measurements in the 1971±1975 and 1982±1984 NHEFS surveys, and current and recalled estimates by subjects in the 1971±1975, 1982±1984, 1986 and 1987 surveys. Height was measured in the 1971±1975 survey. Socio-economic and lifestyle covariates were derived from questionnaires administered in all four surveys. Almost all deaths were veri®ed by death certi®cates. RESULTS: The shape of the morality risk vs baseline BMI curve varied due to a bias (late-life bias) caused by a steep decrease in BMI among the elderly toward the end of the lifespan. In a particular analysis, the portion of subjects at baseline who were deceased elderly with lower BMI than age-matched censored subjects indicated the size of the bias, and appeared to be the proximate cause. Strong evidence was found to support the proximate cause being the actual cause. Excluding deaths during early follow-up was only able to remove the late-life bias in limited circumstances. Using average-adulthood BMI as mortality predictor and baseline BMI as covariate was very effective in removing the late-life bias. It also appeared to remove the reversecausation and regression-dilution biases, and yielded robustly positive mortality risk vs average-adulthood BMI curves in all analyses in which it was tested. CONCLUSIONS: Average-adulthood BMI appears to be an appropriate predictor of mortality risk, provided baseline BMI is used as a covariate. Among non-elderly persons, being leaner meant a lower mortality risk, down to the lowest category of leanness in the study Ð`20 kgam 2 . Future survival analyses of the mortality±BMI relationship should account for the effects of the regression-dilution, reverse-causation and late-life biases.

While plasma leptin and adiposity have been found to be strongly related, the specific nature of this relationship has yet to be clarified. Hence, plasma leptin and three indicators of adiposity were measured in adult male Fischer 344 rats on three different long-term diets: continuous ad libitum feeding; ad libitum feeding until early adulthood, then continuous 60% caloric restriction; and ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, then ad libitum feeding for 5 months. Body fat was found to be a good linear correlate of plasma leptin, with a zero Y-intercept, and a constant plasma leptin-body fat ratio. The number of adipocytes per rat and % body fat were strong quadratic correlates of plasma leptin. This study is the first to find a zero Y-intercept and constant plasma leptin-body fat ratio, probably because it is the first to simultaneously measure both plasma leptin and body fat accurately, and to account for confounders such as gender, genetic background, age, physical activity, and possibly obesity. The study also explored the effect of switching calorically-restricted rats to ad libitum feeding. This led to a rapid rise, and then synchronized up-down cycles in average daily food intake and body weight, with a steady upward trend toward a new stable body-weight set point. It is hypothesized that this pattern resulted from two simultaneous feedback mechanisms, possibly involving leptin. In conclusion, this study suggests that, under controlled conditions, the plasma leptin-body fat ratio is a constant for a particular mammalian strain, independent of dietary history.