Perplexing findings from 2008 connecting better control of blood glucose levels with a higher risk of fatal heart attacks for people with diabetes are now finally being explained by scientists at the Joslin Diabetes Center: a genetic variant is to blame.
Being diagnosed with type 2 diabetes doubles a person’s risk of developing heart disease compared to people without type 2 diabetes. Following up on the 2016 discovery of two genetic variants associated with a major increase of risk for heart disease among people with type 2 diabetes, researchers now understand why, while careful control of blood glucose levels is usually successful at reducing risk of heart disease, the 2008 study showed such stark differences.
The new study from the Joslin Diabetes Center, published in the journal Diabetes Care, identified a hormone called glucagon-like peptide 1 (GLP-1) and its role in diabetes-related heart disease risk when people contain a certain genetic variant, one of the two discovered in 2016. In studies, levels of GLP-1 in people with this particular genetic variant dropped significantly in response to “intensive glycemic control.” Yet, GLP-1 levels stable among people without the variant.
What is GLP-1?
According to the American Heart Association, the “incretin effect” is defined as the difference in insulin secretion between consumption of glucose through a meal and injection of glucose intravenously. People with type 2 diabetes have a reduced or sometimes absent incretin effect, which is responsible for over half of total insulin secretion. GLP-1 is considered an “incretin hormone” because it renews the ability to secrete insulin.
"GLP-1 is produced by intestinal cells, and its main action is to stimulate insulin secretion from beta cells,” explained senior investigator Alessandro Doria, MD, PhD, MPH. “But the hormone also has a beneficial effect on the heart and blood vessels that is independent from its action on insulin secretion.”
Researchers studied 65 biomarkers in 351 participants, comparing intense glucose control and standard glucose control. They were looking for any association between certain biomarkers and the two genetic variants discovered in association with heart disease. In this study, they were able to confirm the link between higher risk of fatal heart attack and lower GLP-1 levels.
Going forward, developing a diagnostic test for people with type 2 diabetes who might have the genetic risk marker associated with GLP-1 would help medical professionals identify which patients would need specific, GLP-1-related drugs.
Next, researchers from this study are going to learn more details: how specifically does the genetic variant influence the production of GLP-1?