The objective of this investigation was to determine the relation between baseline glucose, insulin, adiponectin, and leptin levels and subsequent 6-year weight and waist change in older men and women without diabetes in a prospective cohort study. Participants were 1,198 Dutch men and women without diabetes who were aged 50-77 years when baseline metabolic and anthropometric measurements were evaluated (1989-1991). Approximately 6 years later, body weight and waist circumference were re-measured at a follow-up examination (1996-1998). Metabolic variables (fasting plasma glucose, 2-h postchallenge plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and leptin) were evaluated as predictors of changes in weight and waist circumference. Postchallenge plasma glucose (mmol/l) significantly predicted less gain in both weight and waist circumference (beta = -0.28 kg, s.e. = 0.11; beta = -0.31 cm, s.e. = 0.14, respectively) during follow-up. Leptin (microg/l) significantly predicted greater increases in weight (beta = 0.29 kg, s.e. = 0.07) and waist (beta = 0.16 cm, s.e. = 0.08) among men and in waist among women (beta = 0.06 cm, s.e. = 0.02). Fasting plasma glucose (mmol/l) predicted an increase in waist among women (beta = 1.59 cm, s.e. = 0.63), but not in men (beta = -0.74 cm, s.e. = 0.55). Adiponectin and insulin did not predict weight or waist change. The authors conclude that lower postchallenge plasma glucose and higher fasting leptin levels significantly predicted long-term increases in weight and waist circumference. In contrast, measures of insulin resistance and adiponectin were not associated with weight change in this cohort of older persons without diabetes.Obesity (2009) doi:10.1038/oby.2008.666.