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Risk Factors for Cardiovascular Diabetes and Insulin Resistance

People with diabetes are at increased risk for heart disease. Cardiovascular disease is the leading cause of death in type 1 diabetes, and its burden is also increasing among those with type 2 diabetes. 

A panel at the 2023 Advanced Technologies and Treatments for Diabetes conference in Berlin, Germany, explored this topic and what it means for the most serious complication in diabetes care.

The landmark trial DCCT highlighted the importance of maintaining an A1C less than 7% in reducing the risk of many complications of diabetes. From long-term follow up of the DCCT after the trial was completed and other studies, it became apparent that important factors associated with cardiovascular disease in people with diabetes include blood glucose, blood pressure and cholesterol. While it has long been advised for people with diabetes to discuss these factors with their doctors, new research is emerging revealing additional factors impacting cardiovascular health

Dr. Viral Shah, professor at the Barbara Davis Center for Diabetes at the University of Colorado Medical School and Dr. Antonio Ceriello of Harvard Medical School discussed some of these lesser known factors and where future research might be heading. 

Even among people meeting A1C targets, they were at three times higher risk of death from cardiovascular disease. Shah said that insulin resistance is associated with more frequent cardiovascular disease and is “one of the strongest independent risk factors [for heart disease] in people with type 1 diabetes.”

Ceriello expanded on the risk factors to include liver function. While the connection between the heart and liver may not be immediately clear, liver function can predict how well your heart and kidneys work, he said. For example, people with non-alcoholic steatohepatitis (also known as NASH, a type of liver disease) have an increased risk of heart disease. 

In addition to its anti-obesity benefits, GLP-1s have shown to improve liver and heart function, he detailed. People who took liraglutide (Victoza) and semaglutide (ozempic) for over a year were able to slow the progression of fibrosis and NASH. 

Ceriello said that treating type 2 diabetes and obesity requires interventions to attain the desired cardiometabolic benefits. He said that with the GLP1-RA liraglutide approved for both type 2 diabetes and obesity, meaningful research in this area is underway. For instance, his team investigated the effects of liraglutide on cardiometabolic parameters in subjects with type 2 diabetes and those with obesity, to see whether the outcome varied in relation to obesity. 

“We found that liraglutide had beneficial outcomes on glycemic parameters and cardiometabolic risk factors in both nonobese and obese patients with type 2 diabetes, with greater efficacy in the latter,” Ceriello said. “These findings reinforce the benefits of liraglutide for the cardiometabolic outcomes of obese patients with type 2 diabetes in the real world setting.”

Both GLP1s and SGLT2s have shown to be effective in reducing the major cardiovascular risk factors in people with type 2 diabetes, such as body weight, hyperglycemia, blood pressure and lipids, however the use of these medications on emerging risk factors for CVD, such as liver disease, needs more attention and further research.

 “This remains to be clarified,” Ceriello said. “This is the next step.”

Cardiovascular outcome studies that use GLP1s and SGLT2s have demonstrated how these medications “have changed the landscape of diabetes therapy,” said Dr. Oliver Schnell, endocrinologist specializing in diabetes at Ludwig Maximilian University in Munich. 

Schnell presented an overview of cardiovascular outcome trials (CVOTs) in diabetes, explaining why EASD and ADA guidelines have recommended both GLP1s and SGLT2s for people with type 2 diabetes with heart disease. 

He also detailed the growing need for interventions as the rate of people with diabetes expands at an alarming rate globally. While studies are still being conducted, evidence so far suggests that GLP-1s and SGLT-2s can reduce the major risk factors for cardiovascular disease, including body weight, hyperglycemia, blood pressure and lips, and improved insulin resistance, as well as kidney function. 

Panel moderator Dr. Richard Bergenstal, executive director of the International Diabetes Center at Park Nicollet and clinical professor in the Department of Medicine at the University of Minnesota, said that for so long the message for people with diabetes has been exclusively on tracking glucose levels. 

He said he was encouraged by the growing evidence that other factors also impact cardiovascular health in people with diabetes. 

“Of course diabetes means better glucose management, and that’s always top of mind,” Bergenstal said, “but we are learning that there is so much more one can take into consideration to continue this process of living a longer and healthier life. We’re saying we want you to take a bigger look at other factors, like blood pressure, cholesterol and which medicines you are selecting.”

He was aware that telling people with diabetes to track yet more metrics to monitor their health can seem overwhelming, and although he wanted to avoid adding to the burden of care, he said this latest research expanding the CV risk factors for people with type 2 was encouraging.

“We have made such great strides in glucose management, but there was always this gap, and we could only point to the gap in despair,” Bergenstal said. “But now we have more answers and we know how to close this gap, by paying attention to these other factors. Now there is hope, but it will take work on the part of the person with diabetes and the medical community to get there.”