['Adiponectin and leptin and their ratio have been associated with incident type 2 diabetes (T2DM), although the data presented are conflicting and the populations studied have been small. In this large, prospective, nested, case referent study, we hypothesized that these associations are sex specific and may be modified by insulin resistance.', 'Men and women aged 30-60 years with incident T2DM (n=640) and a prior health survey within the Västerbotten Intervention Programme (VIP) and matched referents (n=1564) were identified. Using conditional logistic regression analyses, we tested whether baseline plasma adiponectin and leptin levels and their ratio independently predicted incident T2DM, stratified for gender and insulin resistance.', 'Adjusted for traditional risk factors, fourth-quartile levels of adiponectin were associated with a reduced risk of T2DM in men [odds ratio (OR) 0.55 (0.36-0.86)] and women [OR 0.47 (0.27-0.83)]. Quartile four of the leptin/adiponectin ratio predicted T2DM in both men [OR 3.08 (1.68-5.67)] and women [OR 3.31 (1.56-7.03)], whereas quartile-four levels of leptin predicted T2DM only in men [OR 2.30 (1.32-4.02)]. When stratified for insulin sensitivity and adjusted for body mass index (BMI), log(e)-transformed leptin predicted T2DM in insulin-sensitive men [OR 1.56 (1.13-2.17)] but not in insulin-resistant men [OR 1.03 (0.76-1.39)]. The effect of adiponectin and the leptin/adiponectin ratio was not influenced by the insulin sensitivity status.'] Is the impact of leptin and adiponectin on incident type 2 diabetes modified by sex and insulin resistance?