In the present study of community dwelling patients with T2D and normal lipid profiles, we found that diabetes significantly impaired HDL endothelial protective functions, as measured by ability of HDL to stimulate eNOS and attenuate NF-κB activation in response to TNFα, despite lack of differences, compared to non-diabetic subjects, in traditional clinical measures associated with metabolic syndrome and cardiovascular risk (HDL-C, TG, LDL-C, BMI, hypertension or CRP). This evidence concerns the gene TNF and type 2 diabetes mellitus.