The aim of the present study was to investigate rs2014355 of ACADS and rs11161510 of ACADM in relation to indices of insulin release, insulin sensitivity, and fasting serum lipid levels in a large random sample of middle-aged individuals (n = 6,162); also we examined the putative relation to T2D prevalence in a case-control study involving ~8,300 Danish individuals (nACADS = 8,313; nACADM = 8,344). This evidence concerns the gene ACADS and type 2 diabetes mellitus.