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Ceramide levels predict T2DM remission following RYGB

Levels of ceramides can also be used to assess the likelihood that a gastric bypass patient will have a recurrence of type 2 diabetes within a decade. A newly developed test could accurately predict whether individuals who undergo gastric bypass surgery will experience a remission of type 2 diabetes within two years of the procedure, according to University of Utah Health scientists.

"These human studies validate our prior findings in rodents that ceramides are major drivers of diabetes,” explained Dr Scott Summers, corresponding author of the study and co-director of the Diabetes Metabolism Research Center. “They also reveal a new tool in the physician's arsenal for managing the health of the increasing number of people undergoing bariatric surgery."

The study, ‘Following Roux-en-Y gastric bypass surgery, serum ceramides demarcate patients that will fail to achieve normoglycemia and diabetes remission’, was published in Med, a Cell Press medical journal.

In previous studies, Summers and his colleagues found that ceramides can reduce the amount of insulin a body can produce or use, increasing the likelihood that a person will develop type 2 diabetes. Intrigued, they decided to examine the association between ceramides, diabetes and severe obesity.

Predicting which patients will have a remission of the disease or a later recurrence has been challenging, said Dr Annelise M Poss, lead author of the study and a former graduate student in Summers' lab.

To address this challenge, Summers, Poss and colleagues analysed blood samples from 1,156 individuals, ages 18-72, collected over a 12-year span. The subjects were divided into three groups:

  • 418 people who underwent gastric bypass surgery

  • 417 who did not have surgery because they were denied insurance coverage; and

  • 321 severely obese individuals who did not consider the surgery.

The researchers chose to have two control groups to account for the possibility that those who were denied insurance coverage were more motivated to diet, exercise, and engage in other weight-loss strategies than those who had no interest in gastric bypass.

Overall, the scientists found that low ceramide levels prior to gastric bypass surgery predicted which patients would achieve remission of the diabetes two years later. Of the 67 gastric bypass patients who had diabetes prior to surgery, 49 (73%) either had transient or sustained remission of their type 2 diabetes. However, those individuals with high ceramides did not achieve diabetes remission, regardless of weight change.

"To our knowledge, this is the first study to evaluate the role that ceramides play in type 2 diabetes disease progression in a severely obese population," explained Poss. "By measuring ceramides in this population, we believe we have detected an important biomarker that can be reliably used to better predict the course of type 2 diabetes among patients who undergo gastric bypass."

Among its limitations, the study did not include a group of lean individuals. As a result, they were unable to determine if ceramide levels influence diabetes progression beyond a severely obese population. The researchers also did not prevent participants from pursuing weight loss interventions or lifestyle changes beyond the scope of the study, which focused specifically on Roux-en-Y, the most common gastric bypass surgery.

Scott Summers and Annalise Poss (Credit: University of Utah Health)

While the data linking high ceramide levels to diabetes is strong, more research is needed before routine ceramide testing can be recommended, Summers added. As part of that effort, the researchers plan to analyze the association between ceramides levels and diabetes progression in other populations.

"The exciting question we want to answer is this: What are the unique factors that are driving ceramides up in some people who are susceptible to diabetes?" he said. "Clearly, it's not just obesity. A major advance would be to find a family or a unique set of individuals who are prone to accumulate ceramides and develop the disease. That would be a big stride toward developing personalized medical care based on these ceramide biomarkers."

Further information

To access this paper, please click here


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