Study Finds Genetic Links Between Diabetes, Heart Disease; Reveals Potential Drug Targets

Connections between type 2 diabetes (T2D) and coronary heart disease (CHD) are well-established—so much so that when a drug is developed to treat one condition, at some point researchers study what happens to patients who have both conditions at once.

But what if scientists could find the common genetic thread and treat both conditions at once? Genome sequence information from 250,000 people has allowed researchers at the University of Pennsylvania’s Perelman School of Medicine to do just that. Reporting in Nature Genetics, the team has identified 16 previously unreported loci for T2D and 1 new loci for CHD; the analysis also uncovered 8 variants that affect both conditions, according to the abstract.

The findings not only raise the possibility of identifying a single common pathway to treat both diseases, but they also help explain puzzles like why some treatments for low-density lipoprotein (LDL) cholesterol can increase risk for T2D. The work opens the door for studies into treatments that can help both conditions without raising new risks for either one, according to the study’s co-senior author, Danish Saleheen, PhD, a Penn assistant professor in Biostatistics and Epidemiology.

"Identifying these gene variants linked to both type 2 diabetes and CHD risk in principle opens up opportunities to lower the risk of both outcomes with a single drug," Saleheen said in a statement. "From a drug development perspective, it would make sense to focus on those pathways that are most strongly linked to both diseases.”

Besides identifying potential new treatment pathways, the study confirmed some existing targets, such as icosapent, an omega-3 fatty acid found in fish oils, which is sold in a prescription strength dose. The study also uncovered dual-risk loci for the area that includes the gene FABP4 (fatty acid binding protein 4), which is already being studied as a drug target. Mouse studies are under way that block this gene’s protein to combat hardening of the arteries and fight diabetes and obesity.

Not all the diabetes-related gene variants worked the same way. According to a statement from Penn Medicine, CHD risk was elevated more by variants linked to obesity and high blood pressure than those that affected insulin or blood glucose levels.

Reference

Zhao W, Rasheed A, Tikkanen E, et al. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease [published online September 4, 2017]. Nat Genetics. 2017; doi:10.1038/ng.3943.