Evaluation of: Kretowski A, McFann K, Hokanson JE et al.: Polymorphisms of the renin–angiotensin system genes predict progression of subclinical coronary atherosclerosis. Diabetes 56, 863–871 (2007). The mechanisms giving rise to the increased risk of coronary artery disease (CAD) in patients with Type 1 diabetes compared with the general population are still incompletely understood. In the study considered here, coronary artery calcification (CAC), a marker of subclinical CAD, was measured over a mean 2.5-year period in approximately 500 subjects with Type 1 diabetes and 500 controls. Polymorphisms in the renin–angiotensin system genes were found to be predictive of CAC progression in diabetic subjects, but only in the absence of treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. This association could help in understanding the development of CAD in diabetic patients. However, because of the dangers of overinterpreting subgroup analyses and multiple testing, the findings require replication in a confirmatory study.