For decades, doctors have known that losing weight can significantly lower risk of heart disease and by extension, reduce the risk of dying from heart-related events such as stroke and heart attack. Studies have shown that both lifestyle changes including diet and exercise as well as medications and weight-loss surgery can improve heart disease risk factors such as obesity and diabetes, for example, but data supporting the benefits of any of these approaches in actually lowering rates of heart events such as heart attack and atrial fibrillation, or in reducing early deaths from heart disease, have been less robust. The data that do exist come from observational studies or smaller trials.

Now a new study, published Sept. 2 in JAMA and simultaneously presented at the European Society of Cardiology annual meeting, takes that previous work a step further, suggesting that weight-loss surgery can lower rates of heart attack, heart failure, atrial fibrillation and stroke, and lower death rates from any cause in a large group of at-risk patients.

A team of researchers led by Dr. Ali Aminian, associate professor of surgery at the Cleveland Clinic, looked at obese patients with type 2 diabetes, who are at higher risk of heart events. Among more than 2,200 such patients who underwent any form of weight-loss surgery, heart-related events dropped by 39% over eight years of follow up and deaths from any cause declined by 41% compared to a group of more than 11,000 matched controls who did not receive any weight loss surgery.

“As a cardiologist, I cannot remember any study, not studies involving statins, or studies involving blood pressure medication, having this large of a treatment effect,” says Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic and senior author of the paper. “What this tells me is that the heart-related morbidity and mortality associated with diabetes and obesity is reversible with the right procedure.”

The magnitude of the reduction in heart events and deaths suggests that the benefits of the surgery may extend beyond those attributable to weight loss alone. “There are neurohormonal changes we see after these procedures that could have significant metabolic effects and benefits for patients,” says Aminian.

The majority of the study participants who had weight-loss surgery underwent gastric bypass, an operation in which surgeons shrink the size of the stomach by creating a small pouch from its tissues and shunting food more directly from that pouch to the upper intestine. The researchers found that, after patients had their digestive tracts re-routed, there were changes in the pattern of hormones their bodies produced. Insulin, produced by beta cells in the pancreas, is responsible for breaking down glucose, and those with diabetes have lower insulin responses to food. But gastric bypass surgery seemed to restore some of the normal insulin response in the study—Aminian found that many patients no longer needed insulin by the end of the study period. In addition, the share of patients relying on non-insulin diabetic medications also dropped, by half, from 80% to nearly 40%.

Weight-loss surgery, and in particular gastric bypass, may also change the composition of healthy bacteria living in the gut. Previous studies have shown that people with diabetes have different species of bacteria in their digestive tract compared to people without diabetes, which may influence how their bodies respond to sugars. In other research in his lab, Aminian has taken fecal samples from patients pre- and post-surgery and transferred them to mice, which acted as simulated human guts. Animals receiving samples from patients before surgery tended to become obese and develop diabetes and fatty liver syndrome, while those receiving samples from patients three months after weight-loss surgery did not.

These findings, taken together, strongly suggest that addressing obesity among diabetics may reverse some of their risk of disease and early death, but that weight loss alone, especially through lifestyle changes such as diet and exercise, may not be enough.

“It’s not just one factor. Weight loss is important, the gut hormones are important, and the microbiome is important,” says Aminian. “They all work together like an orchestra to improve the metabolic condition of the patient.”

He and Nissen agree that weight loss surgery may not be an option for every overweight or obese diabetic patient, but the data suggest that it might be considered for more people in coming years. Because the study did not randomly assign diabetic patients to surgery or the control group, but relied on a matched set of controls for comparison, the next step in confirming the results would be to conduct a randomized control trial. If those findings support these, then a stronger case might be made for considering weight loss surgery for more people.

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