Leveraging Genetics to Improve Cardiovascular Health in Diabetes: The 2018 Edwin Bierman Award Lecture

The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complications of diabetes by allowing us to 1) create predictive algorithms for the identification of patients at especially high risk of CVD so that these individuals can undergo preventive interventions early in the natural history of the disease; 2) discover as yet unknown disease pathways linking diabetes to atherosclerosis, which can be used as targets for the development of new CVD-preventing drugs specifically directed at subjects with diabetes; and 3) devise personalized programs increasing the cost-effectiveness of preventive interventions by tailoring them to the genetic background of each patient. Substantial progress has been made in each of these three areas as exemplified by the recent development of a CHD genetic risk score improving CHD prediction among subjects with type 2 diabetes, the discovery of a diabetes specific CHD locus on 1q25 pointing to glutamine synthase (GLUL) and the gamma-glutamyl cycle as key regulators of CHD risk in diabetes, and the identification of two genetic loci allowing the selection of patients with type 2 diabetes who may especially benefit from intensive glycemic control. Translating these discoveries into clinical practice will not be without challenges, but the potential rewards, from the perspective of public health as well as that of persons with diabetes, make this goal worth pursuing.