Could gene mutation offer new treatment options for cardiometabolic disease?

The scientists involved in the study say that the gene mutation that slows the metabolism of sugar in the gut, gives people who have the mutation a distinct advantage over those who do not: a lower risk of diabetes, obesity, heart failure, and even death. The researchers say their finding could provide a basis for drug therapies that mimic the workings of this gene mutation, offering a potential benefit for the millions of people who suffer with cardiometabolic disease. 

The study was largely supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. 

Commenting on the ramifications of their study findings, Scott D. Solomon MD, a professor of medicine at Harvard Medical School and a senior physician at Brigham and Women’s Hospital in Boston who led the research, said: “We’re excited about this study because it helps clarify the link between what we eat, what we absorb, and our risk for disease. Knowing this opens the door to improved therapies for cardiometabolic disease.”

He explained that the study is the first to fully evaluate the link between mutations in the gene mainly responsible for absorbing glucose in the gut – SGLT-1, or sodium glucose co-transporter-1 – and cardiometabolic disease. 

People who have the natural gene mutation appear to have an advantage when it comes to diet, Solomon noted. Those who eat a high-carbohydrate diet and have this mutation will absorb less glucose than those without the mutation. A high-carbohydrate diet includes starchy foods – such as pasta, potatoes and bread – as well as sugary food and drinks. 

In the study, the researchers analysed the relationship between SGLT-1 mutations and cardiometabolic disease using genetic data obtained from 8,478 participants in the Atherosclerosis Risk In Communities (ARIC) study. The study represented a 25-year-long observational trial of atherosclerosis and cardiovascular risk factors in people living in four U.S. communities.

The researchers found that about 6% of the subjects carried a mutation in SGLT-1 that causes limited impairment of glucose absorption. Individuals with this mutation had a lower incidence of type 2 diabetes, were less obese, had a lower incidence of heart failure, and had a lower mortality rate compared to those without the mutation – even after adjusting for dietary intake (including total calories, sodium and sugars). 

Based on these findings, the scientists suggest that selectively blocking the SGLT-1 receptor could provide a way to slow down glucose uptake to prevent or treat cardiometabolic disease and its consequences. They caution that development of such targeted drugs could take years and that clinical trials are still necessary to determine if the drugs reduce the incidence of diabetes and heart failure and improve lifespan.

The study was published in the Journal of the American College of Cardiology.