Once Type 2 Diabetes is Advanced, Link Between Gut, Hardening of Arteries Weakens

COLUMBUS, Ohio (November 19, 2019) – Diabetes and cardiovascular researchers at The Ohio State University College of Medicine investigated a potentially important link between metabolism in the gut and hardening of the arteries in patients with severe type 2 diabetes.

Researchers studied a metabolite – a specific molecule produced during metabolism in the gut – that in earlier studies had shown an association with greater subsequent cardiovascular events in patients with known coronary artery disease.

More than 30 million Americans have diabetes because their bodies either can't produce enough insulin or can't use insulin efficiently to process food for energy, resulting in too much sugar in the blood. Patients with type 2 diabetes have significant risk of atherosclerotic cardiovascular disease events, including hardening of the arteries, heart attack and stroke, along with other major health problems.

Results of the study published online in the journal BMJ Open Diabetes Research & Care.

“We found that, while this link has shown value in other populations, it didn’t help explain events like heart attack and stroke in this population. These results underscore the value of such collaboration to tackle cardiometabolic disease and identify new treatment targets to help patients with poorly controlled diabetes reduce their risk of heart attack and stroke,” said Dr. Subha Raman, a cardiologist and professor at Ohio State who co-led the research with Dr. Willa Hsueh, director of Ohio State’s Diabetes and Metabolism Research Center.

This study’s physician-scientists worked with Ohio State’s Campus Chemical Instrument Center and collaborators from the University of Maryland and University of Perugia School of Medicine in Italy to analyze available material from participants in the NIH-funded Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

They analyzed data, bio-specimens and major adverse cardiovascular events from the ACCORD trial – one of the largest clinical trials in patients with severe type 2 diabetes – to assess the predictive value of the metabolite trimethylamine N-oxide (TMAO) in 330 high-risk individuals who didn’t have atherosclerotic cardiovascular disease when they enrolled in the trial.

In this cohort of stable high-risk subjects with type 2 diabetes and very similar cardiovascular risk profiles, plasma levels of TMAO weren’t associated with major adverse cardiovascular problems over 4.7 years of follow-up. This study differed from previous ones by focusing on high-risk patients with poorly controlled type 2 diabetes. 

“Our research found that the prognostic value of TMAO for heart attacks and strokes may be blunted when applied to people with type 2 diabetes who have poor glycemic control and high risk of developing hardening of the arteries,” said Hsueh. “Further translational investigations of unique mechanisms of atherosclerotic cardiovascular disease in patients with type 2 diabetes is needed.”