In Brief: New Insight into Metabolic Changes after Weight Loss Surgery

Investigators Link Low Blood Sugar Levels After Eating to Disordered Serotonin Metabolism in People Who Have Had Weight Loss Surgery

A study led by researchers at Joslin Diabetes Center suggests serotonin—a neurotransmitter and hormone that plays important roles throughout the body—may contribute to the abnormally low blood sugar levels (hypoglycemia) experienced by some people who have had weight loss surgery. The study, published in the Journal of Clinical Investigation, sheds light on the complex changes in the gastrointestinal tract that occur in the aftermath of bariatric surgery and provides a potential therapeutic target for post-bariatric hypoglycemia.

Though the mechanisms behind it are not well understood, bariatric surgery results in immediate improvements in glucose metabolism and can even induce remission of type 2 diabetes, demonstrating the gastrointestinal tract’s central role in regulating metabolism. Affecting up to 30 percent of patients who have undergone bariatric surgery, post-bariatric hypoglycemia—in which people develop excessively low blood sugar one to three hours after a meal—is an increasingly recognized and often-severe complication of the procedure. It can manifest as disorientation, slurred speech, shakiness, seizures, and loss of consciousness.

“This condition shows how dramatically glucose metabolism can change after weight loss surgery and studying it could help us better understand how the gut regulates blood sugar,” said corresponding author, Mary Elizabeth Patti, MD, Senior Investigator and Adult Endocrinologist in the Research Division at Joslin Diabetes Center. “This knowledge might also lead to new treatments for the condition and, more generally, to non-surgical ways to improve how the body handles glucose.

Patti and colleagues studied the complete set of molecules produced by metabolism, called the metabolome, present in the blood of people who had undergone bariatric surgery and subsequently experienced PBH compared with people who had bariatric surgery but did not experience symptoms of PBH (as well as a control group of people who had not undergone the surgery.) They analyzed participants’ metabolome, which included molecules such as glucose and the amino acid tryptophan, in the fasting state, and 30 and 120 minutes after eating.

The team observed that the metabolomes of people who had undergone weight loss surgery and experienced PBH were similar to each other but significantly different from those who had had surgery but did not experience symptoms of PBH. Most notably, plasma serotonin—known to play a key role in appetite, digestion and energy expenditure—was nearly twice as high in people with symptoms of PBH versus people who had had bariatric surgery but did not experience PBH.

In a series of experiments in a mouse model, the investigators also showed that inhibiting receptors for serotonin improved glucose metabolism. Taken together, these two findings suggest that serotonin is a key contributor to post-bariatric hypoglycemia, opening the door to a potential therapeutic option for further testing.

Read the full paper in Journal of Clinical Investigation.

BILH Study Authors: Rafael Ferraz-Bannitz, Berkcan Ozturk, Cameron Cummings, Vissarion Efthymiou, Pilar Casanova Querol, Lindsay Poulos, Hanna Wang, Valerie Navarrete, Hamayle Saeed, Christopher M. Mulla, Hui Pan, Jonathan M. Dreyfuss, Mary Elizabeth Patti, MD.

COI: Dr. Patti serves on the data safety monitoring board for Fractyl, has received investigator-initiated research support from Dexcom, and is a consultant for Eiger, Hanmi, and MBX Pharmaceuticals. The other authors declare no competing interests.

Citation: Ferraz-Bannitz R, Ozturk B, Cummings CJ, Efthymiou V, Casanova Querol P, Poulos L, Wang HJ, Navarrete V, Saeed H, Mulla CM, Pan H, Dreyfuss JM, Simonson DC, Sandoval DA, Patti ME. Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia. J Clin Invest. 2024 Sep 12:e180157. doi: 10.1172/JCI180157. Epub ahead of print. PMID: 39264731.

About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Part of Beth Israel Lahey Health, Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is affiliated with Harvard Medical School and one of only 18 NIH-designated Diabetes Research Centers in the United States.