Ceramide Levels Can Predict Failure to Achieve Diabetes Remission After Gastric Bypass

Gregory Weiss, MD

Obesity remains a pervasive health problem around the world putting patients at risk for type 2 diabetes (T2D) and cardiovascular disease.¹

A recent study has uncovered a host of lipid metabolites implicated in creating a so-called lipotoxic state characterized by the deposition of these byproducts in non-adipose tissues leading to dysfunction and disease.¹ One such class of metabolites, the ceramides, may be among the most harmful bioactive lipid species capable of altering the metabolism and survival of healthy cells.¹

With more than 250,000 weight reduction surgeries being performed in the United States annually it is known that patients can lose as much as 30% of their body weight and keep it off for extended periods of time.1 While it is less likely to develop T2D following successful weight reduction surgery it is difficult to predict who will have remission of their diabetes and who will not.

Lead investigator for the study, Annelise Poss, PhD, and colleagues at the University of Utah, building on their prior work, hoped to evaluate the association between ceramides and measures of glycemic control following Roux-en-Y gastric bypass surgery (RYGB).¹ The authors had previously found that ceramides were capable of reducing the amount of insulin a body could produce or utilize, both key features of T2D.² Further building on a handful of prior studies looking at ceramide levels after bariatric surgery, Poss and colleagues further sought to characterize the effect of RYGB on ceramides after weight loss along with measures of insulin sensitivity, glucose control, and diabetes.¹

The authors found that participants with low ceramide levels before RYGB surgery had a higher likelihood of realizing remission of their T2D than those with higher levels.¹ Those with high preoperative ceramide levels, even those with dramatic weight reduction, did not achieve diabetes remission.¹

“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,” Poss said.

In addition to higher ceramide levels being associated with poor remission rates, they were also found to positively correlate with Hemoglobin A1C levels.¹ Ceramide levels continued to decrease consistently among those RYGB patients who realized a sustained remission of their diabetes.¹ Finally, the authors found no relationship between ceramide levels and weight regain, increased cholesterol, or high triglyceride levels post-operatively.¹

Although several key points have been revealed by this research the predictive value of ceramide levels prior to gastric bypass surgery for postoperative remission of diabetes stands out as a potential game changer. While predicting failed remission should not dissuade patients and clinicians from gastric bypass surgery preoperative treatment plans aimed at decreasing levels of this potent lipid metabolite could be an avenue for investigation. Trends in ceremide levels after weight loss surgery may also become a powerful tool for gauging metabolic responses to surgery.¹

Prediction is everything in clinical medicine. With a tool to predict, we can provide a treatment or a procedure with confidence in the outcome. Conversely, we can avoid or counsel patients to avoid treatments, procedures, and lifestyle choices we know may harm.

Bariatric healthcare providers may soon be able to provide obese patients with a more accurate description of their clinical course with or without surgery. In addition to its ability to guide therapy, studying lipid metabolites may unlock the secrets of why people become obese and why excess adiposity contributes so strongly to poor health. In this study, the authors offer up yet another clue to the mystery of metabolic health and illness.

References:

1. Poss et al., Following Roux-en-Y gastric bypass surgery, serum ceramides demarcate patients that will fail to achieve normoglycemia and diabetes remission, Med (2022), https://doi.org/10.1016/j.medj.2022.05.011
2. Meikle, P.J., and Summers, S.A. (2017). Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. Nat. Rev. Endocrinol. 13, 79–91. https://doi. org/10.1038/nrendo.2016.169.